A Case of Spontaneous Intestinal Perforation in Osteogenesis Imperfecta

A 51-year-old male with known osteogenesis imperfecta (OI) (type 1) presented with symptoms and signs of infective endocarditis. Transthoracic echocardiography showed chordal rupture and free mitral regurgitation, resulting in an emergency mitral valve repair. The surgical procedure was largely uneventful but subsequent clinical course on the intensive care unit was complicated by bowel perforation requiring two laparatomies for a colonic resection and loop ileostomy formation. Histology of the excised tissue demonstrated absent musculature with no evidence of ischemia. Spontaneous non-ischemic bowel perforation as a complication of osteogenesis imperfecta is to date unreported. Our case highlights the need for a high index of suspicion of non-ischemic bowel perforation in patients with connective tissue disorders

The Methyltransferase WBSCR22/Merm1 Enhances Glucocorticoid Receptor Function and Is Regulated in Lung Inflammation and Cancer

Glucocorticoids (GC) regulate cell fate and immune function. We identified the metastasis-promoting methyltransferase, metastasis-related methyltransferase 1 (WBSCR22/Merm1) as a novel glucocorticoid receptor (GR) regulator relevant to human disease. Merm1 binds the GR co-activator GRIP1 but not GR. Loss of Merm1 impaired both GR transactivation and transrepression by reducing GR recruitment to its binding sites. This was accompanied by loss of GR-dependent H3K4Me3 at a well characterized promoter. Inflammation promotes GC resistance, in part through the actions of TNFα and IFNγ. These cytokines suppressed Merm1 protein expression by driving ubiquitination of two conserved lysine residues. Restoration of Merm1 expression rescued GR transactivation. Cytokine suppression of Merm1 and of GR function was also seen in human lung explants. In addition, striking loss of Merm1 protein was observed in both inflammatory and neoplastic human lung pathologies. In conclusion, Merm1 is a novel regulator of chromatin structure affecting GR recruitment and function, contributing to loss of GC sensitivity in inflammation, with suppressed expression in pulmonary disease

Crop Updates 2010 - Farming Systems

This session covers twenty papers from different authors: Pests and Disease 1. Preserving phosphine for use in Grain Storage Industry, Christopher R Newman, Department of Agriculture and Food Farming Systems Research 2. Demonstrating the benefits of grazing canola in Western Australia, Jonathan England, Stephen Gherardi and Mohammad Amjad, Department of Agriculture and Food 3. Buloke barley yield when pasture-cropped across subtropical perennial pastures, David Ferris, Department of Agriculture and Food, Phil Ward and Roger Lawes, CSIRO 4. Is pasture cropping viable in WA? Grower perceptions and EverCrop initiatives to evaluate, David Ferris, Tim Wiley, Perry Dolling, Department of Agriculture and Food, Philip Barrett-Lennard, Evergreen farming 5. Best-bet management for dual-purpose canola, John Kirkegaard, Susan Sprague, Hugh Dove and Walter Kelman, CSIRO, Canberra, Peter Hamblin, Agritech Research, Young, NSW 6. Pasture in cropping systems – with and without sheep, Brad Nutt and Angelo Loi, Department of Agriculture and Food 7. Can technology substitute for a lupin break? Wayne Parker, Department of Agriculture and Food 8. Canola row spacing with and without long term stubble retention on a sandy clay loam at Merredin, Glen Riethmuller, Department of Agriculture and Food 9. Impact of stubble retention on water balance and crop yield, Phil Ward1, Ken Flower2,3, Neil Cordingley2 and Shayne Micin1, 1CSIRO, Wembley, Western Australia, 2Western Australian No-Till Farmers Association, 3University of Western Australia Analysis and Modelling 10. Using POAMA rainfall forecasts for crop management in South-West WA, Senthold Asseng1, Peter McIntosh2,3, Mike Pook2,3, James Risbey2,3, Guomin Wang3, Oscar Alves3, Ian Foster4, Imma Farre4 and Nirav Khimashia1, 1CSIRO Plant Industry, Perth, 2CSIRO Marine and Atmospheric Research, Hobart, 3Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne, 4Department of Agriculture and Food 11. Adaption to changing climates and variability – results of the Agribusiness Changing Climates regional workshop, Anderson W3, Beard D3, Blake J3, Grieve R1, Lang M3, Lemon J3, McTaggart R3, Gray D3, Price M2 and Stephens D3, 1Roderick Grieve Farm Management Consultants, 2Coffey International P/L, 3Department of Agriculture and Food 12. Farmers’ management of seasonal variability and climate change in WA, DA Beard, DM Gray, P Carmody, Department of Agriculture and Food 13. Is there a value in having a frost forecast for wheat in South-West WA? Imma Farre1, Senthold Asseng2, Ian Foster1 and Doug Abrecht3, 1Department of Agriculture and Food, CSIRO, Floreat, 2CSIRO Plant Industry, Perth 3Department of Agriculture and Food, Centre for Cropping Systems 14. Does buying rainfall pay? Greg Kirk, Planfarm Agricultural Consultants 15. Which region in the WA wheatbelt makes best use of rainfall? Peter Rowe, Bankwest Agribusiness 16. POAMA – the Predictive Ocean-Atmosphere Model for Australia, Guomin Wang and Oscar Alves, Centre for Australian Weather and Climate Research (CAWCR), A partnership between the Australian Bureau of Meteorology and CSIRO, Melbourne 17. Exploring the link between water use efficiency and farm profitability, Cameron Weeks, Planfarm and Peter Tozer, PRT Consulting Precision Agriculture 18. A plethora of paddock information is available – how does it stack up? Derk Bakker, Department of Agriculture and Food 18. Variable rate prescription mapping for lime inputs based on electromagnetic surveying and deep soil testing, Frank D’Emden, Quenten Knight and Luke Marquis, Precision Agronomics, Australia 19. Trial design and analysis using precision agriculture and farmer’s equipment, Roger Lawes, CSIRO Sustainable Ecosystems, Centre for Environment and Life Sciences, Floreat 20. Farmer perspectives of precision agriculture in Western Australia: Issues and the way forward, Dr Roger Mandel, Curtin Universit

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The relationship between psychological distress and multiple tender points across the adult lifespan

Multiple tender points are common in the population and, in studies of mid-life adults, are strongly associated with high levels of psychological distress. Whether this relationship occurs in older adults is unclear.This cross-sectional study investigated whether high levels of psychological distress would be associated with a high tender point count and whether the relationship would be moderated by age. Three thousand three hundred and seventy-nine individuals were mailed a questionnaire which included the Hospital Anxiety and Depression (HAD) scale, the Pain Catastrophising Scale (PCS), the Brief Illness Perception Questionnaire (Brief IPQ), and the Pittsburgh Sleep Quality Index (PSQI). A random sample of approximately 10% of subjects who returned the questionnaire undertook a physical assessment, including a manual tender point count assessment.A total of 2385 (71%) subjects completed the questionnaire, of whom 798 (33%) were invited to take part in the physical assessment and 290 (12%) participated. Of the 290 participants the median age was 64 years (range 34–97) and 63% were female. The median HAD score was 9 (IQR 5–14) and the median number of tender points was 3 (range 0–7).Increasing HAD score was positively and significantly associated with tender point count, but this relationship was not moderated by age. In a final multivariable model, sex, HAD score and PSQI score were independent predictors of multiple tender points.Psychological distress was associated with multiple tender points independent of age. Psychological distress and trouble sleeping were important, potentially modifiable factors associated with the outcome

Social capital, individual responses to heat waves and climate change adaptation: An empirical study of two UK cities

It has been claimed that high social capital contributes to both positive public health outcomes and to climate change adaptation. Strong social networks have been said to support individuals and collective initiatives of adaptation and enhance resilience. As a result, there is an expectation that social capital could reduce vulnerability to risks from the impacts of climate change in the health sector. This paper examines evidence on the role social networks play in individuals’ responses to heat wave risk in a case study in the UK. Based on interviews with independently living elderly people and their primary social contacts in London and Norwich, we suggest that strong bonding networks could potentially exacerbate rather than reduce the vulnerability of elderly people to the effects of heat waves. Most respondents interviewed did not feel that heat waves posed a significant risk to them personally, and most said that they would be able to cope with hot weather. Bonding networks could perpetuate rather than challenge these narratives and therefore contribute to vulnerability rather than ameliorating it. These results suggest a complex rather than uniformly positive relationship between social capital, health and adaptation to climate change