CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial pneumonia.

OBJECTIVES: In patients with septic shock, circulating monocytes become refractory to stimulation with microbial products. Whether this hyporesponsive state is induced by infection or is related to shock is unknown. To address this question, we measured TNF alpha production by monocytes or by whole blood obtained from healthy volunteers (controls), from patients with septic shock, from patients with severe infection (bacterial pneumonia) without shock, and from patients with cardiogenic shock without infection. MEASUREMENTS: The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes or whole blood were stimulated with lipopolysaccharide endotoxin (LPS), heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production was measured by bioassay. RESULTS: The number of circulating monocytes, of CD14+ monocytes, and the monocyte CD14 expression were significantly lower in patients with septic shock than in controls, in patients with bacterial pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole blood of patients with septic shock exhibited a profound deficiency of TNF alpha production in response to all stimuli (p < 0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p < 0.05 compared to controls), although to a lesser extent, despite normal monocyte counts and normal CD14 expression. CONCLUSIONS: Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF alpha production in response to a broad range of infectious stimuli. Thus, down-regulation of cytokine production appears to occur in patients with systemic, but not localised, albeit severe, infections and also in patients with non-infectious circulatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors are at work in this group and in patients with cardiogenic shock.

Taxation and Total Government Take from the UK Continental Shelf (UKCS) Following Phase 3 of the European Emissions Trading Scheme (EU ETS)

NORTH SEA STUDY OCCASIONAL PAPER No. 117

Slowing Down

We extend the efficiency wage model of Shapiro and Stiglitz to account for the observation that workers’ effort has a tendency to fall when they approach the end of their employment contract. In particular, we find that the efficiency wage increases when the end of term approaches for a given rate of unemployment. We draw implications for the behavior of workers who are approaching retirement, temporary employment contracts, and the advance notice of impending job loss.

VEGF and TNF up-regulate, NSAID down-regulate SOX18 protein level in HUVEC

Angiogenesis, the process of generating new blood vessels, is essential to embryonic development, organ formation, tissue regeneration and remodeling, reproduction and wound healing. Also, it plays an important role in many pathological conditions, including chronic inflammation and cancer. Angiogenesis is regulated by a complex interplay of growth factors, inflammatory mediators, adhesion molecules, morphogens and guidance molecules. Transcription factor SOX18 is transiently expressed in nascent endothelial cells during embryonic development and postnatal angiogenesis, but little is known about signaling pathways controlling its expression. The aim of this study was to investigate whether pro-angiogenic molecules and pharmacological inhibitors of angiogenesis modulate SOX18 expression in endothelial cells. Therefore, we treated human umbilical vein endothelial cells (HUVEC) with angiogenic factors, extracellular matrix proteins, inflammatory cytokines and nonsteroidal anti-inflammatory drugs (NSAID) and monitored SOX18 expression. We have observed that the angiogenic factor VEGF and the inflammatory cytokine TNF increase, while the NSAID ibuprofen and NS398 decrease the SOX18 protein level. These results for the first time demonstrate that SOX18 expression is modulated by factors and drugs known to positively or negatively regulate angiogenesis. This opens the possibility of pharmacological manipulation of SOX18 gene expression in endothelial cells to stimulate or inhibit angiogenesis.

Oligodendroglia metabolically support axons and contribute to neurodegeneration.

Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.

Skin Cancer Prevention Strategy and Action Plan (PDF 455KB)

Northern Ireland may not enjoy the sunniest climate in the world, or even in the UK, however, in spite of this we have witnessed a significant rise in the incidence of melanoma skin cancer cases in recent years - from 80 cases in 1984 to 282 in 2009 (the latest year for which published figures are available). In relation to non-melanoma skin cancers, there are approximately 2,850 new cases here each year, making it the most common type of cancer diagnosed in Northern Ireland. åÊ The rise in the number of skin cancer cases is alarming. We know that the increase in this particular type of cancer is global and not just confined to our part of the world. We also know there are many factors involved: the significant rise in people travelling on foreign sun holidays; more leisure time being spent out of doors; and damage caused to the ozone layer to name but a few. åÊ Substantial progress in the area of skin cancer awareness raising and prevention has been made through the previous “Melanoma Strategy” which was developed in 1997. However, the unfortunate reality is that we will continue to see rising rates of skin cancer for some time to come as a result of many years of overexposure to the sun before skin cancer prevention programmes were developed. Until we can reverse this trend through effective campaigning and awareness raising, early detection will be key to bringing down mortality rates. While the 1997 strategy was right for its time, there have been many developments since then, necessitating a new strategy to reflect today’s position. åÊ For example, recent studies about the importance of vitamin D have highlighted the need for balance in sun safety messages. This new strategy is not about stopping people from enjoying the sun and its many benefits. Rather, it is about encouraging people to take proportionate measures to prevent overexposure. åÊ åÊ

Development of Public Health Nursing within Public Health Nursing in the Poleglass Twinbrook and Lagmore Areas of Down Lisburn Trust (PDF 424 KB)

Project evaluation report on the development of public health nursing within children's services in areas of Down Lisburn Trust. Part of the Department's redesign of community nursing project

Development of spatial integration depends on top-down and interhemispheric connections that can be perturbed in migraine: a DCM analysis.

In humans, spatial integration develops slowly, continuing through childhood into adolescence. On the assumption that this protracted course depends on the formation of networks with slowly developing top-down connections, we compared effective connectivity in the visual cortex between 13 children (age 7-13) and 14 adults (age 21-42) using a passive perceptual task. The subjects were scanned while viewing bilateral gratings, which either obeyed Gestalt grouping rules [colinear gratings (CG)] or violated them [non-colinear gratings (NG)]. The regions of interest for dynamic causal modeling were determined from activations in functional MRI contrasts stimuli > background and CG > NG. They were symmetrically located in V1 and V3v areas of both hemispheres. We studied a common model, which contained reciprocal intrinsic and modulatory connections between these regions. An analysis of effective connectivity showed that top-down modulatory effects generated at an extrastriate level and interhemispheric modulatory effects between primary visual areas (all inhibitory) are significantly weaker in children than in adults, suggesting that the formation of feedback and interhemispheric effective connections continues into adolescence. These results are consistent with a model in which spatial integration at an extrastriate level results in top-down messages to the primary visual areas, where they are supplemented by lateral (interhemispheric) messages, making perceptual encoding more efficient and less redundant. Abnormal formation of top-down inhibitory connections can lead to the reduction of habituation observed in migraine patients.

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening.

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7-22.4) for trisomy 21, 5.0 (95% CI 4.8-5.1) for trisomy 18 and 2.0 (95% CI 1.9-2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9-11.5) for trisomy 21, 1.04 (95% CI 0.96-1.12) for trisomy 18 and 0.48 (95% CI 0.43-0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.

Bowel cancer screening: how to take the test (English and 10 translations)

Format: 6 page A5 leaflet Target group: Prospective participants in the Northern Ireland Bowel cancer screening programme Description: This leaflet provides step by step instructions on using the Faecal Occult Blood test (FOBt) for bowel cancer screening.

Down-modulation of lymphoproliferation and interferon-gamma production by beta-glucan derived from Saccharomyces cerevisiae

beta-glucan, one of the major cell wall components of Saccharomyces cerevisiae, has been found to enhance immune functions. This study investigated in vivo and in vitro effects of beta-glucan on lymphoproliferation and interferon-gamma (IFN-gamma) production by splenic cells from C57BL/6 female mice. All experiments were performed with particulate beta-glucan derived from S. cerevisiae. Data demonstrated that both, i.p administration of particulate beta-glucan (20 or 100 µg/animal) and in vitro stimulation of splenic cells (20 or 100 µg/ml of culture) decreased lymphoproliferation and IFN-gamma production induced by concanavalin A. These results suggest that beta-glucan can trigger a down-modulatory effect regulating a deleterious immune system hyperactivity in the presence of a strong stimulus.