Illness perceptions of gout patients and the use of allopurinol in primary care: baseline findings from a prospective cohort study

Background Patients’ perceptions of their illness are dynamic and can directly influence aspects of management. Our aim was to examine the illness perceptions of gout patients in UK primary care and associations with allopurinol use. Methods A health questionnaire was sent to 1805 people with gout aged ≥18 years identified by a gout diagnosis or prescriptions for allopurinol or colchicine in their primary care medical records in the preceding 2 years. The questionnaire included selected items from the revised illness perception questionnaire (IPQ-R). Associations between illness perceptions and use of allopurinol were calculated using multinomial logistic regression adjusted for age, gender, deprivation status, body mass index, alcohol consumption, comorbidities and gout characteristics. Results One thousand one hundred eighty-four participants responded to the baseline questionnaire (65.6 %). Approximately half of responders perceived that they were able to control (51.2 %) or affect their gout through their own actions (44.8 %). Three quarters perceived treatments to be effective (76.4 %) and agreed that gout is a serious condition (76.4 %). Patients who agreed that they could control their gout (Relative Risk Ratio, 95 % confidence interval 1.66 (1.12 to 2.45)) and that treatments were effective (2.24 (1.32 to 3.81)) were more likely to currently be using allopurinol than not using allopurinol. However, this significance was attenuated after adjustment for self-reported gout characteristics (1.39 (0.89 to 2.17) & 1.78 (0.96 to 3.29) respectively). Conclusions Patients who perceive that they can control their gout and that treatments are effective are more likely to be using allopurinol, this suggests that better information is needed for the patient from GPs and rheumatologist to reassure and support their use of UL

Children with autism deserve evidence-based intervention

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Jennifer J Couper and Amanda J Sampso

Generating SQL queries from visual specifications

Abstract: Structured Query Language (SQL) is the most widely used declarative language for accessing relational databases, and an essential topic in introductory database courses in higher learning institutions. Despite the intuitiveness of SQL, formulating and comprehending written queries can be confusing, especially for undergraduate students. One major reason for this is that the simple syntax of SQL is often misleading and hard to comprehend. A number of tools have been developed to aid the comprehension of queries and improve the mental models of students concerning the underlying logic of SQL. Some of these tools employed visualisation and animation in their approach to aid the comprehension of SQL. This paper presents an interactive comprehension aid based on visualisation, specifically designed to support the SQL SELECT statement, an area identified in the literature as problematic for students. The visualisation tool uses visual specifications depicting SQL operations to build queries. This is expected to reduce the cognitive load of a student who is learning SQL. We have shown with an online survey that adopting visual specifications in teaching systems assist students in attaining a richer learning experience in introductory database courses

Multilocus Phylogenetic Study of the Scheffersomyces Yeast Clade and Characterization of the N-Terminal Region of Xylose Reductase Gene

Many of the known xylose-fermenting (X-F) yeasts are placed in the Scheffersomyces clade, a group of ascomycete yeasts that have been isolated from plant tissues and in association with lignicolous insects. We formally recognize fourteen species in this clade based on a maximum likelihood (ML) phylogenetic analysis using a multilocus dataset. This clade is divided into three subclades, each of which exhibits the biochemical ability to ferment cellobiose or xylose. New combinations are made for seven species of Candida in the clade, and three X-F taxa associated with rotted hardwood are described: Scheffersomyces illinoinensis (type strain NRRL Y-48827T  =  CBS 12624), Scheffersomyces quercinus (type strain NRRL Y-48825T  =  CBS 12625), and Scheffersomyces virginianus (type strain NRRL Y-48822T  =  CBS 12626). The new X-F species are distinctive based on their position in the multilocus phylogenetic analysis and biochemical and morphological characters. The molecular characterization of xylose reductase (XR) indicates that the regions surrounding the conserved domain contain mutations that may enhance the performance of the enzyme in X-F yeasts. The phylogenetic reconstruction using XYL1 or RPB1 was identical to the multilocus analysis, and these loci have potential for rapid identification of cryptic species in this clade

Measurement of the total antioxidant response using a novel automated method in subjects with nonalcoholic steatohepatitis

BACKGROUND: Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of nonalcoholic steatohepatitis. We aimed to investigate the total antioxidant response using a novel automated method in nonalcoholic steatohepatitis subjects. As a reciprocal measure, we also aimed to determine total peroxide level in the same plasma samples. METHODS: Twenty-two subjects with biopsy proven nonalcoholic steatohepatitis and 22 healthy controls were enrolled. Total antioxidant response and total peroxide level measurements were done in all participants. The ratio percentage of total peroxide level to total antioxidant response was regarded as oxidative stress index. RESULTS: Total antioxidant response of subjects with nonalcoholic steatohepatitis was significantly lower than controls (p < 0.05), while mean total peroxide level and mean oxidative stress index were higher (all p < 0.05). In subjects with nonalcoholic steatohepatitis, fibrosis score was significantly correlated with total peroxide level, total antioxidant response and oxidative stress index (p < 0.05, r = 0.607; p < 0.05, r = -0.506; p < 0.05, r = 0.728, respectively). However, no correlation was observed between necroimflamatory grade and those oxidative status parameters (all p > 0.05). CONCLUSION: Nonalcoholic steatohepatitis is associated with increased oxidant capacity, especially in the presence of liver fibrosis. The novel automated assay is a reliable and easily applicable method for total plasma antioxidant response measurement in nonalcoholic steatohepatitis

Hospitalizations for acetaminophen overdose: a Canadian population-based study from 1995 to 2004

<p>Abstract</p> <p>Background</p> <p>Acetaminophen overdose (AO) is the most common cause of acute liver failure. We examined temporal trends and sociodemographic risk factors for AO in a large Canadian health region.</p> <p>Methods</p> <p>1,543 patients hospitalized for AO in the Calgary Health Region (population ~1.1 million) between 1995 and 2004 were identified using administrative data.</p> <p>Results</p> <p>The age/sex-adjusted hospitalization rate decreased by 41% from 19.6 per 100,000 population in 1995 to 12.1 per 100,000 in 2004 (<it>P </it>< 0.0005). This decline was greater in females than males (46% vs. 29%). Whereas rates fell 46% in individuals under 50 years, a 50% increase was seen in those ≥ 50 years. Hospitalization rates for intentional overdoses fell from 16.6 per 100,000 in 1995 to 8.6 per 100,000 in 2004 (2004 vs. 1995: rate ratio [RR] 0.49; <it>P </it>< 0.0005). Accidental overdoses decreased between 1995 and 2002, but increased to above baseline levels by 2004 (2004 vs. 1995: RR 1.24;<it>P </it>< 0.0005). Risk factors for AO included female sex (RR 2.19; <it>P </it>< 0.0005), Aboriginal status (RR 4.04; <it>P </it>< 0.0005), and receipt of social assistance (RR 5.15; <it>P </it>< 0.0005).</p> <p>Conclusion</p> <p>Hospitalization rates for AO, particularly intentional ingestions, have fallen in our Canadian health region between 1995 and 2004. Young patients, especially females, Aboriginals, and recipients of social assistance, are at highest risk.</p

Alteration of EGFR Spatiotemporal Dynamics Suppresses Signal Transduction

The epidermal growth factor receptor (EGFR), which regulates cell growth and survival, is integral to colon tumorigenesis. Lipid rafts play a role in regulating EGFR signaling, and docosahexaenoic acid (DHA) is known to perturb membrane domain organization through changes in lipid rafts. Therefore, we investigated the mechanistic link between EGFR function and DHA. Membrane incorporation of DHA into immortalized colonocytes altered the lateral organization of EGFR. DHA additionally increased EGFR phosphorylation but paradoxically suppressed downstream signaling. Assessment of the EGFR-Ras-ERK1/2 signaling cascade identified Ras GTP binding as the locus of the DHA-induced disruption of signal transduction. DHA also antagonized EGFR signaling capacity by increasing receptor internalization and degradation. DHA suppressed cell proliferation in an EGFR-dependent manner, but cell proliferation could be partially rescued by expression of constitutively active Ras. Feeding chronically-inflamed, carcinogen-injected C57BL/6 mice a fish oil containing diet enriched in DHA recapitulated the effects on the EGFR signaling axis observed in cell culture and additionally suppressed tumor formation. We conclude that DHA-induced alteration in both the lateral and subcellular localization of EGFR culminates in the suppression of EGFR downstream signal transduction, which has implications for the molecular basis of colon cancer prevention by DHA

Rationale, design and methods for a randomised and controlled trial to evaluate "Animal Fun" - a program designed to enhance physical and mental health in young children

Background: Children with poor motor ability have been found to engage less in physical activities than other children, and a lack of physical activity has been linked to problems such as obesity, lowered bone mineral density and cardiovascular risk factors. Furthermore, if children are confident with their fine and gross motor skills, they are more likely to engage in physical activities such as sports, crafts, dancing and other physical activity programs outside of the school curriculum which are important activities for psychosocial development. The primary objective of this project is to comprehensively evaluate a whole of class physical activity program called Animal Fun designed for Pre-Primary children. This program was designed to improve the child's movement skills, both fine and gross, and their perceptions of their movement ability, promote appropriate social skills and improve social-emotional development. Methods: The proposed randomized and controlled trial uses a multivariate nested cohort design to examine the physical (motor coordination) and psychosocial (self perceptions, anxiety, social competence) outcomes of the program. The Animal Fun program is a teacher delivered universal program incorporating animal actions to facilitate motor skill and social skill acquisition and practice. Pre-intervention scores on motor and psychosocial variables for six control schools and six intervention schools will be compared with post-intervention scores (end of Pre-Primary year) and scores taken 12 months later after the children's transition to primary school Year 1. 520 children aged 4.5 to 6 years will be recruited and it is anticipated that 360 children will be retained to the 1 year follow-up. There will be equal numbers of boys and girls.Discussion: If this program is found to improve the child's motor and psychosocial skills, this will assist in the child's transition into the first year of school. As a result of these changes, it is anticipated that children will have greater enjoyment participating in physical activities which will further promote long term physical and mental health

Soil Microbial Responses to Elevated CO2 and O3 in a Nitrogen-Aggrading Agroecosystem

Climate change factors such as elevated atmospheric carbon dioxide (CO2) and ozone (O3) can exert significant impacts on soil microbes and the ecosystem level processes they mediate. However, the underlying mechanisms by which soil microbes respond to these environmental changes remain poorly understood. The prevailing hypothesis, which states that CO2- or O3-induced changes in carbon (C) availability dominate microbial responses, is primarily based on results from nitrogen (N)-limiting forests and grasslands. It remains largely unexplored how soil microbes respond to elevated CO2 and O3 in N-rich or N-aggrading systems, which severely hinders our ability to predict the long-term soil C dynamics in agroecosystems. Using a long-term field study conducted in a no-till wheat-soybean rotation system with open-top chambers, we showed that elevated CO2 but not O3 had a potent influence on soil microbes. Elevated CO2 (1.5×ambient) significantly increased, while O3 (1.4×ambient) reduced, aboveground (and presumably belowground) plant residue C and N inputs to soil. However, only elevated CO2 significantly affected soil microbial biomass, activities (namely heterotrophic respiration) and community composition. The enhancement of microbial biomass and activities by elevated CO2 largely occurred in the third and fourth years of the experiment and coincided with increased soil N availability, likely due to CO2-stimulation of symbiotic N2 fixation in soybean. Fungal biomass and the fungi∶bacteria ratio decreased under both ambient and elevated CO2 by the third year and also coincided with increased soil N availability; but they were significantly higher under elevated than ambient CO2. These results suggest that more attention should be directed towards assessing the impact of N availability on microbial activities and decomposition in projections of soil organic C balance in N-rich systems under future CO2 scenarios

Increased Membrane Cholesterol in Lymphocytes Diverts T-Cells toward an Inflammatory Response

Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40–50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4+ Foxp3+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response