MicroRNA-146a is upregulated by and negatively regulates TLR2 signaling

TLR signaling is a crucial component of the innate immune response to infection. MicroRNAs (miRNAs) have been shown to be upregulated during TLR signaling. Specifically, microRNA-146a (miR-146a) plays a key role in endotoxin tolerance by downregulating interleukin-1 receptor-associated kinase 1 (IRAK-1). The aim of this study was to assess the role of miR-146a in the TLR2 signaling and development of bacterial lipoprotein (BLP) self-tolerance and cross-tolerance to bacteria. Expression of miR-146a increased in a dose- and time-dependent manner in BLP-stimulated human THP-1 promonocytic cells. In BLP-tolerised cells miR-146a was even further upregulated in response to BLP re-stimulation (p,0.001). Restimulation of BLP-tolerised cells with heat-killed gram-negative Salmonella typhimurium (S. typhimurium), but not grampositive Staphylococcus aureus (S. aureus), led to significant overexpression of miR-146a (p,0.05). Transfection of naive cells with a miR-146a mimic substantially suppressed TNF-a production (p,0.05). Furthermore, overexpression of miR-146a resulted in strong reduction in IRAK-1 and phosphorylated IkBa expression in naive and S. typhimurium-stimulated THP-1 cells. Collectively, miR-146a is upregulated in response to BLP and bacterial stimulation in both naive and BLP-tolerised cells. Overexpression of miR-146a induces a state analogous to tolerance in BLP-stimulated cells and therefore may represent a future target for exogenous modulation of tolerance during microbial infection and sepsi

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas

This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0·0086). We quantified the risk of perinatal transmission and the age-dependent rate of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers

Self-regulation: A new perspective on learning problems experienced by children born extremely preterm

Survival rates are increasing for children born extremely preterm, yet despite the majority of these children having IQ scores within the average range, 50-70% of these children have later school difficulties. This paper reviews factors associated with academic difficulties in these children, emphasizing the contributions of executive functions (EF) and self-regulation. The roles of EF are examined separately, and also under the unifying construct of self-regulation; that is, the integration of various behavioural, cognitive, and affective elements. Improving self-regulatory skills could moderate the negative effects of EF deficits and inform interventions to improve the educational outcomes of these childre

Design of automatic milking system for use in pasture-based systems

End of Project ReportA commercial vision system was successful in identifying target artificial teats in various and demanding scenarios, but the system is very prone to making false identifications. A robotic manipulator capable of the simultaneous handling of four milking cups has been designed. The end-effector profile is sufficiently compact to allow access between the rear legs of the cow while enabling full access to all four teats for application of milking cups. The positioning response of the end-effecter is satisfactory for accommodating small changes in teat position during milking cup application

Self-report versus care provider registration of healthcare utilization: impact on cost and cost-utility

OBJECTIVES: This study aims to compare the impact of two different sources of resource use, self-report versus care provider registrations, on cost and cost utility. METHODS: Data were gathered for a cost-effectiveness study performed alongside a 2-year randomized controlled trial evaluating the effect of an INTERdisciplinary COMmunity-based management program (INTERCOM) for patients with chronic obstructive pulmonary disease (COPD). The program was offered by physiotherapists, dieticians and respiratory nurses. During the 2-year period, patients reported all resource use in a cost booklet. In addition, data on hospital admissions and outpatient visits, visits to the physiotherapist, dietician or respiratory nurse, diet nutrition, and outpatient medication were obtained from administrative records. The cost per quality-adjusted life-year (QALY) was calculated in two ways, using data from the cost booklet or registrations. RESULTS: In total, 175 patients were included in the study. Agreement between self-report and registrations was almost perfect for hospitalizations (rho = 0.93) and physiotherapist visits (rho = 0.86), but above 0.55, moderate, for all other types of care. The total cost difference between the registrations and the cost booklet was 464 euros with the highest difference for hospitalizations 386 euro. Based on the cost booklet the cost difference between the treatment group and usual care was 2,444 euros (95 percent confidence interval [CI], -819 to 5,950), which resulted in a cost-utility of 29,100 euro/QALY. For the registrations, the results were 2,498 euros (95 percent CI, -88 to 6,084) and 29,390 euro/QALY, respectively. CONCLUSIONS: This study showed that the use of self-reported data or data from registrations effected within-group costs, but not between-group costs or the cost utility

Gadolinium-Enhanced Magnetic Susceptibility Contrast Is Reduced in the Corpus Callosum of a Mouse Model of Tauopathy

Alterations to white matter have been implicated in a number of neurodegenerative diseases. In this work we investigate the sensitivity of MRI magnetic susceptibility mapping to these changes using a mouse model of Tauopathy. A non-rigid registration of contrast enhanced, high resolution ex vivo mouse brain images is used to transform susceptibility maps into a common space and a voxel-wise group comparison is performed. Significant differences were observed that may indicate disruption to the tissue of the corpus callosum

Maternal Anxiety and Depression, Poverty and Marital Relationship Factors During Early Childhood as Predictors of Anxiety and Depressive Symptoms in Adolescence

BACKGROUND This paper examines the degree to which symptoms of anxiety and depression at age 14 years are associated with early childhood experience of maternal anxiety and depression, poverty, and mother's marital relationship distress and break-up. METHODS In a longitudinal study, 4434 families were followed-up from infancy to adolescence. RESULTS: Maternal anxiety and depression during early childhood were found to have small, but significant, influences upon the development of high anxiety-depression symptoms at age 14, after controlling for the effects of poverty and marital relationship factors. This effect was greater with repeated exposure to high maternal anxiety and depression. Poverty, distressed marital relationship and marital break-up during the child's first five years also produced small, but significant, increases in risk of high anxiety and depression symptoms in adolescence. Stable, single-parent status was not found to be a risk factor. There was no evidence of marked gender differences in risk factors, other than poverty, which had a stronger impact for girls than boys. CONCLUSIONS Overall, the results suggest that maternal anxiety and depression, poverty, parent relationship conflict and marital break-up during early childhood are associated with small, but significant, increased risk of anxiety-depression symptoms in adolescence

Influence of organic and mineral amendments on microbial soil properties and processes

Microbial diversity in soils is considered important for maintaining sustainability of agricultural production systems. However, the links between microbial diversity and ecosystem processes are not well understood. This study was designed to gain better understanding of the effects of short-term management practices on the microbial community and how changes in the microbial community affect key soil processes. The effects of different forms of nitrogen (N) on soil biology and N dynamics was determined in two soils with organic and conventional management histories that varied in soil microbial properties but had the same fertility. The soils were amended with equal amounts of N (100 kg ha⁻¹) in organic (lupin, Lupinus angustifolius L.) and mineral form (urea), respectively. Over a 91-day period, microbial biomass C and N, dehydrogenase enzyme activity, community structure of pseudomondas (sensu stricto), actinomycetes and α proteobacteria (by denaturing gradient gel electrophoresis (DGGE) following PCR amplification of 16S rDNA fragments) and N mineralisation were measured. Lupin amendment resulted in a two- to five-fold increase in microbial biomass and enzyme activity, while these parameters did not differ significantly between the urea and control treatments. The PCR–DGGE analysis showed that the addition of mineral and organic compounds had an influence on the microbial community composition in the short term (up to 10 days) but the effects were not sustained over the 91-day incubation period. Microbial community structure was strongly influenced by the presence or lack of substrate, while the type of amendment (organic or mineral) had an effect on microbial biomass size and activity. These findings show that the addition of green manures improved soil biology by increasing microbial biomass and activity irrespective of management history, that no direct relationship existed among microbial structure, enzyme activity and N mineralisation, and that microbial community structure (by PCR–DGGE) was more strongly influenced by inherent soil and environmental factors than by short-term management practices

The association of hypertensive disorders of pregnancy with weight gain over the subsequent 21 years: Findings from a prospective cohort study

Obesity is an important risk factor for hypertensive disorders of pregnancy, but most cases of hypertensive disorders of pregnancy occur in women of normal weight. There may be predisposing factors to both hypertensive disorders of pregnancy and obesity. To test this hypothesis, the authors compared changes in body mass index (weight (kg)/height (m)(2)) overtime in women with and without hypertensive disorders of pregnancy. They used data from 3,572 women who received antenatal care at a major public hospital in Brisbane, Australia, between 1981 and 1984 and who were followed up for 21 years. A total of 318 women (8.9%) had experienced hypertensive disorders in the index pregnancy, and 233 of them (73.3%) had a baseline body mass index of = 5 kg/m(2) were 59% greater for women who experienced hypertensive disorders of pregnancy compared with those who did not (odds ratio = 1.59, 95% confidence interval: 1.24, 2.04). The authors concluded that hypertensive disorders of pregnancy are associated with increased weight gain over 21 years