Structural characterisation of the capsular polysaccharide expressed by Burkholderia thailandensis strain E555:: wbiI (pKnock-KmR) and assessment of the significance of the 2-O-acetyl group in immune protection

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Burkholderia pseudomallei and its close relative B. mallei are human pathogens that are classified as Tier 1 bio-threat agents. Both organisms have previously been shown to constitutively produce a capsular polysaccharide (CPS) that is both a virulence determinant and protective antigen. Extraction and purification of CPS for use as a potential vaccine candidate requires containment level 3 laboratories which is expensive and time-consuming. B. thailandensis strain E555 is closely related to B. pseudomallei and B. mallei, but is non-pathogenic to humans and based on immunological cross-reactivity has previously been shown to express a B. pseudomallei-like CPS. In this study, capsular polysaccharide isolated from an O-antigen deficient strain of B. thailandensis E555 was identified by 1H and 13C NMR spectroscopy as -3-)-2-O-acetyl-6-deoxy-β-d-manno-heptopyranose-(-1, and identical to that produced by B. pseudomallei. This was further substantiated by anti-CPS monoclonal antibody binding. In connection with the production of CPS fragments for use in glycoconjugate vaccines, we set out to assess the importance or otherwise of the CPS 2-OAc groups in immune protection. To this end conjugates of the native and de-O-acetylated CPS with the Hc fragment of tetanus toxin (TetHc) were used as vaccines in a mouse model of melioidosis. The level of protection provided by deacetylated CPS was significantly lower than that from native, acetylated CPS. In addition, sera from mice vaccinated with the deacetylated CPS conjugate did not recognise native CPS. This suggests that CPS extracted from B. thailandensis can be used as antigen and that the acetyl group is essential for protection.This research was funded by the US Defence Threat Reduction Agency (DTRA), grant CBBAA12-VAXBT2-1-0032 and the United Kingdom Ministry of Defence. Studies at the JIC were supported by the UK BBSRC Institute Strategic Programme on Understanding and Exploiting Metabolism (MET) [BB/J004561/1] and the John Innes Foundation. MID was supported by a BBSRC Industrial CASE award with Mologic Ltd

The impact of ambient temperature on mortality among the urban population in Skopje, Macedonia during the period 1996–2000

BACKGROUND: This study assesses the relationship between daily numbers of deaths and variations in ambient temperature within the city of Skopje, R. Macedonia. METHODS: The daily number of deaths from all causes, during the period 1996–2000, as well as those deaths from cardiovascular diseases, occurring within the city of Skopje were related to the average daily temperature on the same day using Multiple Regression statistical analyses. Temperature was measured within the regression model as two complementary variables: 'Warm' and 'Cold'. Excess winter mortality was calculated as winter deaths (deaths occurring in December to March) minus the average of non-winter deaths (April to July of the current year and August to November of the previous year). RESULTS: In this study the average daily total of deaths was 7% and 13% greater in the cold when compared to the whole period and warm period respectively. The same relationship was noticed for deaths caused by cardiovascular diseases. The Regression Beta Coefficient (b = -0.19) for the total mortality as a function of the temperature in Skopje during the period 1996–2000 was statistically significant with negative connotation as was the circulatory mortality due to average temperature (statistically significant regression Beta coefficient (b = -0.24)). A measure of this increase is provided, on an annual basis, in the form of the excess winter mortality figure. CONCLUSION: Mortality with in the city of Skopje displayed a marked seasonality, with peaks in the winter and relative troughs in the summer

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Clinical Observation Study of Massive Blood Transfusion in a Tertiary Care Hospital in Korea

PURPOSE: Massive blood transfusios are uncommon. The goal of this study was to propose an ideal ratio for the blood component of massive hemorrhage treatment after review of five years of massive transfusion practice, in order to have the best possible clinical outcomes. MATERIALS AND METHODS: We defined a 'massive transfusion' as receiving 10 or more units of red blood cells in one day. A list of patients receiving a massive transfusion from 2004 to 2008 was generated using the electronic medical records. For each case, we calculated the ratio of blood components and examined its relationship to their survival. RESULTS: Three hundred thirty four patients underwent massive transfusion during the five years of the study. The overall seven-day hospital mortality for massive transfusion patients was 26.1%. Factors independently predictive of survival were a fresh-frozen plasma (FFP)/packed red blood cell (pRBC) ratio ≥ 1.1 with an odds ratio (OR) of 1.96 (1.03-3.70), and elective admission with an OR of 2.6 (1.52-4.40). The receiver operation characteristic (ROC) curve suggest that a 1 : 1 : 1 ratio of pRBCs to FFP to platelets is the best ratio for survival. CONCLUSION: Fixing blood-component ratios during active hemorrhage shows improved outcomes. Thus, the hospital blood bank and physician hypothesized that a fixed blood component ratio would help to reduce mortality and decrease utilization of the overall blood componentope

HAE therapies: past present and future

Advances in understanding the pathophysiology and mechanism of swelling in hereditary angioedema (HAE) has resulted in the development of multiple new drugs for the acute and prophylactic treatment of patients with HAE. This review will recap the past treatment options, review the new current treatment options, and discuss potential future treatment options for patients with HAE

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Cancer incidence in the south Asian population of England (1990–92)

Cancer incidence among English south Asians (residents in England with ethnic origins in India, Pakistan or Bangladesh) is described and compared with non-south Asian and Indian subcontinent rates. The setting for the study was areas covered by Thames, Trent, West Midlands and Yorkshire cancer registries. The study identified 356 555 cases of incident cancer (ICD9:140–208) registered between 1990 and 1992, including 3845 classified as English south Asian. The main outcome measures were age specific and directly standardized incidence rates for all cancer sites (ICD9:140–208). English south Asian incidence rates for all sites combined were significantly lower than non-south Asian rates but higher than Indian subcontinent rates. English south Asian rates were substantially higher than Indian subcontinent rates for a number of common sites including lung cancer in males, breast cancer in females and lymphoma in both sexes. English south Asian rates for childhood and early adult cancer (0–29 years) were similar or higher than non-south Asian rates. English south Asian rates were significantly higher than non-south Asian rates for Hodgkin's disease in males, cancer of the tongue, mouth, oesophagus, thyroid gland and myeloid leukaemia in females, and cancer of the hypopharynx, liver and gall bladder in both sexes. The results are consistent with a transition from the lower cancer risk of the country of ethnic origin to that of the country of residence. They suggest that detrimental changes in lifestyle and other exposures have occurred in the migrant south Asian population. © 1999 Cancer Research Campaig