Randomised comparison of guided self management and traditional treatment of asthma over one year.

OBJECTIVE: To compare the efficacy of self management of asthma with traditional treatment. DESIGN: 12 month prospective randomised trial. SETTING: Outpatient clinics in Finland. SUBJECTS: 115 patients with mild to moderately severe asthma. INTERVENTIONS: Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements. MAIN OUTCOME MEASURES: Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life. RESULTS: The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare. CONCLUSIONS: Self management reduces incidents caused by asthma and improves quality of life.     

Genetics of Callous-Unemotional Behavior in Children

Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU.     

Probe-level estimation improves the detection of differential splicing in Affymetrix exon array studies

The recent advent of exon microarrays has made it possible to reveal differences in alternative splicing events on a global scale. We introduce a novel statistical procedure that takes full advantage of the probe-level information on Affymetrix exon arrays when detecting differential splicing between sample groups. In comparison to existing ranking methods, the procedure shows superior reproducibility and accuracy in distinguishing true biological findings from background noise in high agreement with experimental validations.     

Unique cytokine secretion profile in children with both type I diabetes and asthma distinct from that of solely diabetic or asthmatic children

Asthma and type I diabetes are major causes of chronic illness in childhood which, according to the current paradigm, have mutually antagonistic immunopathologies. Nonetheless, the disorders appear to preferably coexist both on population and individual levels. To assess whether children with asthma and type I diabetes might have a common immunoregulatory defect. The spontaneous and anti-CD3+ anti-CD28-stimulated cytokine production patterns by peripheral blood mononuclear cells of 13 children with both asthma and diabetes, nine children with diabetes, 11 children with asthma and nine healthy children were assessed using cytometric bead assay. The spontaneous production of IFN-gamma, TNF-alpha and IL-10 by mononuclear cells in children with both asthma and diabetes was elevated compared to the other study groups (p=0.02, p=0.001 and p=0.04, respectively). Stimulation in vitro increased IL-10 secretion in solely diabetic (p=0.008), asthmatic (p=0.008) and healthy children (p=0.01), but not in children with both diseases (p=0.22). Children suffering from both diabetes and asthma display a unique cytokine secretion pattern, distinct from those of solely diabetic, asthmatic and healthy children. In particular, these children appear to have a defect in regulation of IL-10 secretion.     

Presence of 1→3-linked 2-O-β-d-xylopyranosyl-α-l-arabinofuranosyl side chains in cereal arabinoxylans

The presence of a fairly uncommon side chain 2-O-β-d-xylopyranosyl-α-l-arabinofuranosyl in arabinoxylans (AX) from eight different cereal by-products was investigated, using ¹H NMR spectroscopy and high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) after Shearzyme^® (GH10 endo-1,4-β-d-xylanase) hydrolysis. This disaccharide side group was present in significant amounts in AX extracted from corn cobs and barley husks. For the first time, it was also detected in AX from oat spelts and rice husks, and in lesser amounts in wheat straw AX. Arabinoxylo-oligosaccharide (AXOS) containing the 2-O-β-d-Xylp-α-l-Araf side chain was purified from the oat spelt AX hydrolysate and the structure was fully analyzed using 1D and 2D NMR spectroscopy. The AXOS was identified as β-d-Xylp-(1→2)-α-l-Araf-(1→3)-β-d-Xylp-(1→4)-d-Xyl. To our knowledge, such a structure with 2-O-β-d-Xylp-α-l-Araf attached to the O-3 of the nonreducing end of xylobiose has not been described previously. New information on substitution of AX from various cereal by-products was obtained by combining NMR and enzyme-assisted HPAEC-PAD analysis.     

Cool and Hot Executive Function Impairments in Violent Offenders with Antisocial Personality Disorder with and without Psychopathy

Background

Impairments in executive function characterize offenders with antisocial personality disorder (ASPD) and offenders with psychopathy. However, the extent to which those impairments are associated with ASPD, psychopathy, or both is unknown.

Methods

The present study examined 17 violent offenders with ASPD and psychopathy (ASPD+P), 28 violent offenders with ASPD without psychopathy (ASPD−P), and 21 healthy non-offenders on tasks assessing cool (verbal working memory and alteration of motor responses to spatial locations) and hot (reversal learning, decision-making under risk, and stimulus-reinforcement-based decision-making) executive function.

Results

In comparison to healthy non-offenders, violent offenders with ASPD+P and those with ASPD−P showed similar impairments in verbal working memory and adaptive decision-making. They failed to learn from punishment cues, to change their behaviour in the face of changing contingencies, and made poorer quality decisions despite longer periods of deliberation. Intriguingly, the two groups of offenders did not differ significantly from the non-offenders in terms of their alteration of motor responses to spatial locations and their levels of risk-taking, indicated by betting, and impulsivity, measured as delay aversion. The performance of the two groups of offenders on the measures of cool and hot executive function did not differ, indicating shared deficits.

Conclusions

These documented impairments may help to explain the persistence of antisocial behaviours despite the known risks of the negative consequences of such behaviours.     

Dengue in Travelers: Kinetics of Viremia and NS1 Antigenemia and Their Associations with Clinical Parameters

Despite the increasing numbers of travel-acquired dengue, few studies have assessed virologic markers of the disease in non-endemic populations. We examined the kinetics of diagnostic markers and their associations with clinical parameters in 93 patients with travel-acquired dengue fever. Kinetics analyses suggested a longer average duration for viremia (9 days, CI95%: 8–10) and non-structural protein 1 (NS1) antigenemia (15 days, CI95%: 12–20) than reported in endemic populations. While none of the tests sufficed alone, the best diagnostic coverage was achieved by combining antibody detection with RNA or NS1 testing. Studied by regression models, early relative levels of viremia and NS1 antigenemia proved to be significantly associated with several clinical parameters: high viremia predicted greater likelihood and increased length of hospitalization, the degree of NS1 antigenemia correlated positively with hematocrit and liver transaminases, and both viremia and NS1 antigenemia levels negatively with platelet counts in follow-up. Levels of viremia and NS1 antigenemia may serve as predictors of the clinical manifestations in travel-acquired dengue.     

Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8^−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a HDL elevating effect of Osbpl8 knock-out and additional gender- and/or diet-dependent impacts on lipid metabolism.