Phylogenetic analysis of porcine circovirus type 2 (PCV2) pre- and post-epizootic postweaning multisystemic wasting syndrome (PMWS)

The porcine circovirus type 2 (PCV2) genome encodes three major open reading frames (ORFs) encoding the replicase proteins (ORF1), the viral capsid protein (ORF2), and a protein with suggested apoptotic activity (ORF3). Previous phylogenetic analyses of complete genome sequences of PCV2 from GenBank have demonstrated 95-100% intra-group nucleotide sequence identity. However, although these isolates were readily grouped into clusters and clades, there was no correlation between the occurrence of specific PCV2 genotypes and the geographic origin or health status of the pig. In the present study, a unique dataset from a field study spanning the years pre and post the recognition of postweaning multisystemic wasting syndrome (PMWS) in Sweden was utilized. Using this dataset it was possible to discriminate three Swedish genogroups (SG1-3) of PCV2, of which SG1 was recovered from a pig on a healthy farm ten years before the first diagnosis of PMWS in Sweden. The SG1 PCV2/ORF2 gene sequence has been demonstrated to exhibit a high genetic stability over time and has subsequently only been demonstrated in samples from pigs on nondiseased farms. In contrast, SG2 was almost exclusively found on farms that had only recently broken down with PMWS whereas the SG3 genogroup predominated in pigs from PMWS-affected farms. These results further support the results obtained from earlier in vitro and in vivo experimental models and suggest the association of specific PCV2 genogroups with diseased and nondiseased pigs in the field.

Lack of in vitro and in vivo effects of lipopolysaccharide on porcine circovirus type 2 infection

Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome (PMWS). The presence of immunostimulating factors or concurrent infections seems to be crucial for PMWS development. Lipopolysaccharide (LPS) is a potent immunological activator and has recently been suggested to enhance PCV2 replication in vitro. This study was designed to evaluate the effects of different LPS products on PCV2 in vitro replication of pulmonary macrophages (PMs), and on the potential ability to trigger PMWS in cesarean-derived, colostrum-deprived (CDCD) PCV2-inoculated piglets. In vitro studies using two different PCV2 isolates (Stoon-1010 and 1452/3) showed the presence of PCV2 antigen within the cytoplasm to a variable degree; PCV2 Stoon-1010 was barely detectable (

Temporal distribution of porcine circovirus 2 genogroups recovered from postweaning multisystemic wasting syndrome-affected and -nonaffected farms in Ireland and Northern Ireland

Porcine circovirus type 2 (PCV2) is now recognized as the essential infectious component of porcine postweaning multisystemic wasting syndrome (PMWS). PMWS was first recognized in high-status, specific pathogen-free pigs in Canada in 1991 and is now an economically important disease that affects the swine industry around the world. Recently, reports of genomic studies on PCV2 viruses indicated that 2 distinctive genogroups of PCV2 exist.(4,10) This report involves the results of a study on the distribution of predominant PCV2 genogroups recovered from samples taken from PMWS-affected and PMWS-nonaffected farms on the island of Ireland over a 9-year period and the results of a study on PCV2 genogroup recovery from fecal samples taken from a farm in Northern Ireland from 2003 to 2005 that was first diagnosed as PMWS positive in August 2005. The results indicate that, although at least 2 distinct genogroups of PCV2 have been circulating on pig farms on the island of Ireland, there does not appear to be a direct relationship between infection with these different genogroups of PCV2 and the development of PMWS.

T lymphocyte epitope mapping of porcine circovirus type 2

Immunoreactive T lymphocyte epitopes within the ORF1, ORF2, and ORF 3 products of porcine circovirus type 2 (PCV2) were mapped. For this, overlapping linear 20-mer peptides were synthesized and tested for their ability to induce T lymphocyte proliferation in porcine peripheral blood mononuclear cells (PBMCs) isolated from experimentally PCV2-infected pigs. After a preliminary screening of 31 (ORF1), 23 (ORF2), and 10 (ORF3) peptides using PBMCs from 4 PCV2-infected pigs, none of the peptides appeared to be immunoreactive (stimulation index [SI] : 2) in all four pigs. Only 14 peptides appeared to be immunoreactive in 3 of the 4 pigs. These peptides were designated as immunodominant in the preliminary screening and selected for further analysis. The immunodominant peptides were resynthesized and purified by high-performance liquid chromatography and tested for their ability to induce T lymphocyte proliferation in PBMCs from another three PCV2-infected pigs. None of the immunodominant peptides appeared to be immunoreactive in all three pigs of the second screening. Only three peptides appeared to be immunoreactive in two of three pigs, two encoded by PCV2 ORF1 (amino acid residues 81-100 and 201-220) and one encoded by PCV2 ORF3 (amino acid residues 31-50), and were therefore considered to be immunodominant in both screenings. Although peptides encoded by ORF2 appeared to show the highest immunoreactivity in some pigs, none of these peptides displayed immunodominance in both screenings. In summary, the present study indicates that the T lymphocyte responses to PCV2 are primarily directed toward epitopes of the nonstructural proteins of ORF1 and ORF3.

A revised age for the Kawakawa/Oruanui tephra, a key marker for the Last Glacial Maximum in New Zealand

The Kawakawa/Oruanui tephra (KOT) is a key chronostratigraphic marker in terrestrial and marine deposits of the New Zealand (NZ) sector of the southwest Pacific. Erupted early during the Last Glacial Maximum (LGM), the wide distribution of the KOT enables inter-regional alignment of proxy records and facilitates comparison between NZ climatic variations and those from well-dated records elsewhere. We present 22 new radiocarbon ages for the KOT from sites and materials considered optimal for dating, and apply Bayesian statistical methods via OxCal4.1.7 that incorporate stratigraphic information to develop a new age probability model for KOT. The revised calibrated age, ±2 standard deviations, for the eruption of the KOT is 25,360 ± 160 cal yr BP. The age revision provides a basis for refining marine reservoir ages for the LGM in the southwest Pacific.

Family caregivers' ideal expectations of Canada's Compassionate Care Benefit

We present the findings of 57 interviews conducted in 2007-2008 with Canadians who have cared for a dying family member to examine their ideal expectations of the Compassionate Care Benefit (CCB) - a social programme providing job security and income support for workers caring for a dying person. Our aims are to (1) appreciate how intended users and other family caregivers view the programme's very nature; (2) identify programme challenges and improvements that emerge from considering family caregivers' ideal expectations; and (3) contribute to a larger evaluative study designed to make policy-relevant recommendations for CCB improvement. Review of transcripts across three respondent groups reveals four categories of ideal expectations: (1) eligibility, (2) informational, (3) timing and (4) financial. Ideal expectations were typically derived from respondents' experiences of care-giving, their knowledge of the programme and, for some, of applying for and/or receiving the CCB. Findings reveal that there are gaps between respondents' ideal expectations and their experienced realities. Such gaps may lead to disappointment being experienced by those who believe they should be eligible for the programme but are not, or should be entitled to receive some form of support that is not presently available. This analysis plays an important role in identifying potential changes for the CCB that may better support family caregivers, in that the ideal expectations serve as a starting point for articulating desirable programme amendments. This analysis also has wider relevance. For jurisdictions looking to create new social programmes to support caregivers based upon labour policy strategies and legislation, this analysis identifies considerations that should be made at the outset of development. For jurisdictions that already have employment-based caregiver support programmes, this analysis demonstrates that programme challenges may not always be met through legislative changes alone but also through measures such as increasing awareness. © 2011 Blackwell Publishing Ltd.

Canada's Compassionate Care Benefit:Is it an adequate public health response to addressing the issue of caregiver burden in end-of-life care?

Background: An increasingly significant public health issue in Canada, and elsewhere throughout the developed world, pertains to the provision of adequate palliative/end-of-life (P/EOL) care. Informal caregivers who take on the responsibility of providing P/EOL care often experience negative physical, mental, emotional, social and economic consequences. In this article, we specifically examine how Canada's Compassionate Care Benefit (CCB) - a contributory benefits social program aimed at informal P/EOL caregivers - operates as a public health response in sustaining informal caregivers providing P/EOL care, and whether or not it adequately addresses known aspects of caregiver burden that are addressed within the population health promotion (PHP) model. Methods. As part of a national evaluation of Canada's Compassionate Care Benefit, 57 telephone interviews were conducted with Canadian informal P/EOL caregivers in 5 different provinces, pertaining to the strengths and weaknesses of the CCB and the general caregiving experience. Interview data was coded with Nvivo software and emerging themes were identified by the research team, with such findings published elsewhere. The purpose of the present analysis was identified after comparing the findings to the literature specific to caregiver burden and public health, after which data was analyzed using the PHP model as a guiding framework. Results: Informal caregivers spoke to several of the determinants of health outlined in the PHP model that are implicated in their burden experience: gender, income and social status, working conditions, health and social services, social support network, and personal health practises and coping strategies. They recognized the need for improving the CCB to better address these determinants. Conclusions: This study, from the perspective of family caregivers, demonstrates that the CCB is not living up to its full potential in sustaining informal P/EOL caregivers. Effort is required to transform the CCB so that it may fulfill the potential it holds for serving as one public health response to caregiver burden that forms part of a healthy public policy that addresses the determinants of this burden. © 2011 Williams et al; licensee BioMed Central Ltd.

In Situ Single-Crystal Diffraction Studies of the Structural Transition of Metal-Organic Framework Copper 5-Sulfoisophthalate, Cu-SIP-3

The flexibility of the metal-organic framework Cu-2(OH)(C8H3O7S)(H2O)center dot 2H(2)O (Cu-SIP-3) toward reversible single-crystal to single-crystal transformations is demonstrated using in situ diffraction methods at variable temperature. At temperatures below a dehydration-induced phase transition (T < 370 K) the structure is confirmed as being hydrated. In the temperature range where the transition takes place (370 K < T < 405 K) no discrete, sharp Bragg peaks can be seen in the single-crystal X-ray diffraction pattern, indicating significant loss of long-range order. At temperatures higher than 405 K, the Bragg peaks return and the structure can be refined as dehydrated Cu-SIP-3. The loss of guest water molecules can be followed at temperatures below the phase transition giving insight into the mechanism of the dehydration. Addition of nitric oxide gas to the material above the gating opening pressure of 275 mbar also leads to loss of Bragg scattering in the diffraction pattern.

High-resolution reconstruction of atmospheric deposition of trace metals and metalloids since AD 1400 recorded by ombrotrophic peat cores in Hautes-Fagnes, Belgium

The objective of our study was to determine the trace metal accumulation rates in the Misten bog, Hautes-Fagnes, Belgium, and assess these in relation to established histories of atmospheric emissions from anthropogenic sources. To address these aims we analyzed trace metals and metalloids (Pb, Cu, Ni, As, Sb, Cr, Co, V, Cd and Zn), as well as Pb isotopes, using XRF, Q-ICP-MS and MC-ICP-MS, respectively in two 40-cm peat sections, spanning the last 600 yr. The temporal increase of metal fluxes from the inception of the Industrial Revolution to the present varies by a factor of 5–50, with peak values found between AD 1930 and 1990. A cluster analysis combined with Pb isotopic composition allows the identification of the main sources of Pb and by inference of the other metals, which indicates that coal consumption and metallurgical activities were the predominant sources of pollution during the last 600 years.

High population prevalence of cardiac troponin I measured by a high-sensitivity assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish Cohort

Aims
Our aim was to test the prediction and clinical applicability of high-sensitivity assayed troponin I for incident cardiovascular events in a general middle-aged European population.

Methods and results
High-sensitivity assayed troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340) with 2171 cardiovascular events (including acute coronary heart disease and probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980 myocardial infarctions, and 797 strokes of all kinds during an average of 20 years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by the high-sensitivity method was associated with future cardiovascular risk after full adjustment such as that individuals in the fourth category had 2.5 times the risk compared with those without detectable troponin I (P < 0.0001). These associations remained significant even for those individuals in whom levels of contemporary-sensitivity troponin I measures were not detectable. Addition of troponin I levels to clinical variables led to significant increases in risk prediction with significant improvement of the c-statistic (P < 0.0001) and net reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in men is suggested to detect individuals at high risk for future cardiovascular events.

Conclusion
Troponin I, measured with a high-sensitivity assay, is an independent predictor of cardiovascular events and might support selection of at risk individuals.

Educational interventions in neurology:A comprehensive systematic review

A fear of neurology and neural sciences (neurophobia) may have clinical consequences. There is therefore a need to formulate an evidence-based approach to neurology education. A comprehensive systematic review of educational interventions in neurology was performed. BEI, Cochrane Library, Dialog Datastar, EBSCO Biomedical, EBSCO Psychology & Behavioral Sciences, EMBASE, ERIC, First Search, MDConsult, Medline, Proquest Medical Library and Web of Knowledge databases were searched for all published studies assessing interventions in neurology education among undergraduate students, junior medical doctors and residents up to and including July 2012. Two independent literature searches were performed for relevant studies, which were then classified for level of evidence using the Centre of Evidence-based Medicine criteria and four levels of Kirkpatrick educational outcomes. One systematic review, 16 randomized controlled trials (RCTs), nine non-randomized cohort/follow-up studies, 33 case series or historically controlled studies and three mechanism-based reasoning studies were identified. Educational interventions showed favourable evaluation or assessment outcomes in 15 of 16 (94%) RCTs. Very few studies measured subsequent clinical behaviour (two studies) and patient outcomes (one study). There is very little high quality evidence of demonstrably effective neurology education. However, RCTs are emerging, albeit without meeting comprehensive educational criteria. An improving evidence base in the quality of neurology education will be important to reduce neurophobia. © 2013 EFNS.

IL-33 attenuates the development of experimental autoimmune uveitis

Interleukin (IL)-33 is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ(+) and IL-17(+) CD4(+) T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization towards an alternatively-activated macrophage (M2) phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis.