bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice
Authors: Hamzah Juliana , Kotamraju Venkata R. , Seo Jai W. , Agemy Lilach , Fogal Valentina , Mahakian Lisa M. , Peters David , Roth Lise , Gagnon M. Karen J. , Ferrara Katherine W. , Ruoslahti Erkki
Published: April 2011

The ability to selectively deliver compounds into atherosclerotic plaques would greatly benefit the detection and treatment of atherosclerotic disease. We describe such a delivery system based on a 9-amino acid cyclic peptide, LyP-1. LyP-1 was originally identified as a tumor-homing peptide that specifically recognizes tumor cells, tumor lymphatics, and tumor-associated macrophages. As the receptor for LyP-1, p32, is expressed in atherosclerotic plaques, we tested the ability of LyP-1 to home to plaques. Fluorescein-labeled LyP-1 was intravenously injected into apolipoprotein E (ApoE)-null mice that had been maintained on a high-fat diet to induce atherosclerosis. LyP-1 accumulated in the plaque interior, predominantly in macrophages. More than 60% of cells released from plaques were positive for LyP-1 fluorescence. Another plaque-homing peptide, CREKA, which binds to fibrin-fibronectin clots and accumulates at the surface of plaques, yielded fewer positive cells. Tissues that did not contain plaque yielded only traces of LyP-1+cells. LyP-1 was capable of delivering intravenously injected nanoparticles to plaques; we observed abundant accumulation of LyP-1–coated superparamagnetic iron oxide nanoparticles in the plaque interior, whereas CREKA-nanoworms remained at the surface of the plaques. Intravenous injection of 4-[18F]fluorobenzoic acid ([18F]FBA)-conjugated LyP-1 showed a four- to sixfold increase in peak PET activity in aortas containing plaques (0.31% ID/g) compared with aortas from normal mice injected with [18F]FBA-LyP-1(0.08% ID/g,P <0.01) or aortas from atherosclerotic ApoE mice injected with [18F]FBA-labeled control peptide (0.05% ID/g,P< 0.001). These results indicate that LyP-1 is a promising agent for the targeting of atherosclerotic lesions.
A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor
Authors: Chabot Sophie , Jabrane-Ferrat Nabila , Bigot Karine , Tabiasco Julie , Provost Alexandra , Golzio Muriel , Noman Muhammad Zaeem , Giustiniani Jérôme , Bellard Elisabeth , Brayer Stéphanie , Aguerre-Girr Maryse , Meggetto Fabienne , Giuriato Sylvie , Malecaze François , Galiacy Stéphane , Jaïs Jean-Philippe , Chose Olivier , Kadouche Jean , Chouaib Salem , Teissié Justin , Abitbol Marc , Bensussan Armand , Le Bouteiller Philippe
Published: April 2011

Angiogenesis plays an essential role in several diseases of the eye and in the growth of solid tumors, but existing antiangiogenic therapies have limited benefits in several cases. We report the antiangiogenic effects of a monoclonal antibody, CL1-R2, in several animal models of neovascularization. CL1-R2 recognizes human CD160, a membrane receptor which is conserved in various mammal species. We show that CD160 is expressed on the endothelial cells of newly formed blood vessels in human colon carcinoma and mouse B16 melanoma but not in vessels of healthy tissues. CL1-R2 reduced fibroblast growth factor 2–induced neovascularization in the rabbit cornea, in a mouse model of oxygen-induced retinopathy, and in a mouse Matrigel plug assay. Treatment of B16 melanoma-bearing mice with CL1-R2 combined with cyclophosphamide chemotherapy caused regression of the tumor vasculature and normalization of the remaining vessels as shown by Doppler ultrasonography, intravital microscopy, and histology. These studies validate CD160 as a potential new target in cases of human pathological ocular and tumor neoangiogenesis that do not respond or become resistant to existing antiangiogenic drugs.
A simple cost-effective and scale-less empirical approach to harvest strategies
Authors: Prince Jeremy D. , Dowling Natalie A. , Davies Campbell R. , Campbell Robert A. , Kolody Dale S.
Published: April 2011

Prince, J. D., Dowling, N. A., Davies, C. R., Campbell, R. A., and Kolody, D. S. 2011. A simple cost-effective and scale-less empirical approach to harvest strategies. – ICES Journal of Marine Science, 68: 947–960. An empirical harvest strategy for an Australian longline fishery was developed and tested using harvest strategy evaluation. The approach is based on catch rate and size composition indices and iteratively drives the population towards a target level of spawning potential ratio. The simulation model assumed traditional age-structured population dynamics. The results demonstrate that the empirical approach represents a promising feedback strategy that becomes more precautionary as data errors and recruitment variance increase. Given the urgent need for formal harvest strategies to replace ad hoc decision-making in data-poor fisheries, the approach offers considerable promise. Independent implementation at local scales across the range of a species is speculated to result in management that is robust to uncertainty about stock structure.
Predicting habitat to optimize sampling of Pacific sardine (Sardinops sagax)
Authors: Zwolinski Juan P. , Emmett Robert L. , Demer David A.
Published: April 2011

Zwolinski, J. P., Emmett, R. L., and Demer, D. A. 2011. Predicting habitat to optimize sampling of Pacific sardine (Sardinops sagax). – ICES Journal of Marine Science, 68: 867–879. More than 40 years after the collapse of the fishery for Pacific sardine, a renewed fishery has emerged off the west coasts of the United States and Canada. The daily egg production method (DEPM) and acoustic-trawl surveys are performed annually and, to minimize the uncertainties in the estimates, sampling effort needs to be allocated optimally. Here, based on a 12-year dataset including the presence/absence of sardine eggs and concomitant remotely sensed oceanographic variables, a probabilistic generalized additive model is developed to predict spatio-temporal distributions of habitat for the northern stock of Pacific sardine in the California Current. Significant relationships are identified between eggs and sea surface temperature, chlorophyll a concentration, and the gradient of sea surface altitude. The model accurately predicts the habitat and seasonal migration pattern of sardine, irrespective of spawning condition. The predictions of potential habitat are validated extensively by fishery landings and net-sample data from the northeast Pacific. The predicted habitat can be used to optimize the time and location of the DEPM, acoustic-trawl, and aerial surveys of sardine. The method developed and illustrated may be applicable too to studies of other stocks of sardine and other epipelagic fish in other eastern boundary, upwelling regions.
Using bycatch data to understand habitat use of small cetaceans: lessons from an experimental driftnet fishery
Authors: Stenson Garry B. , Benjamins Steven , Reddin David G.
Published: April 2011

Stenson, G. B., Benjamins, S., and Reddin, D. G. 2011. Using bycatch data to understand habitat use of small cetaceans: lessons from an experimental driftnet fishery. – ICES Journal of Marine Science, 68: 937–946. Many marine mammals inhabit offshore areas where it is difficult to determine distribution and abundance. Historical bycatch data of marine mammals in the Northwest Atlantic obtained from the Canadian experimental Atlantic salmon (Salmo salar) driftnet fishery were examined to obtain information on seasonal distribution and relative abundance. From 1965 to 2001, 47 cruises were undertaken totalling 12 566.5 km-h of fishing effort; four species of small cetacean and two species of pinniped were caught. Harbour porpoises (Phocoena phocoena) were the most frequently caught species in all areas except the Labrador Sea, where Atlantic white-sided dolphins (Lagenorhynchus acutus) were more common. Long-finned pilot whales (Globicephala melas), common dolphins (Delphinus delphis), harp seals (Pagophilus groenlandicus), and harbour seals (Phoca vitulina) were also taken occasionally. Although typically considered an inshore species, harbour porpoises were regularly reported in deep water (>2000 m), in the Newfoundland Basin and Labrador Sea. Atlantic white-sided dolphins were often caught along the edge of the continental shelf and appeared to prefer relatively warm water. Finally, catch records indicate that waters of the Newfoundland Basin and Southern Grand Banks may contain important winter habitat for several small species of cetacean.
Genetic identification of farmed and wild Atlantic cod, Gadus morhua, in coastal Norway
Authors: Glover Kevin A. , Dahle Geir , Jørstad Knut E.
Published: April 2011

Glover, K. A., Dahle, G., and Jørstad, K. E. 2011. Genetic identification of farmed and wild Atlantic cod, Gadus morhua, in coastal Norway. – ICES Journal of Marine Science, 68: 901–910. Each year thousands of Atlantic cod escape from Norwegian fish farms. To investigate the potential for the genetic identification of farmed–escaped cod in the wild, three case studies were examined. Samples of farmed, recaptured farmed escapees, and wild cod were screened for ten microsatellite loci and the Pan I locus. Variable genetic differences were observed among cod sampled from different farms and cages (pairwise FST = 0.0–0.1), and in two of the case studies, the most likely farm(s) of origin for most of the recaptured escapees were identified. In case study 2, wild cod were genetically distinct from both farmed fish (pairwise FST = 0.026–0.06) and recaptured farmed–escaped cod (pairwise FST = 0.029 and 0.039), demonstrating the potential to detect genetic interactions in that fjord. Genetic identification of escapees was more challenging in case study 3, and some morphologically characterized wild cod were found to most likely represent farmed escapees. It is concluded that where cod are farmed in the same region as their own parents/grandparents were initially sourced, or where farmed escapees originate from multiple sources, quantifying genetic interactions with wild populations will be challenging with neutral or nearly neutral markers such as microsatellites.
Tissue-Specific Regulation of Gibberellin Biosynthesis in Developing Pea Seeds
Authors: Nadeau Courtney D. , Ozga Jocelyn A. , Kurepin Leonid V. , Jin Alena , Pharis Richard P. , Reinecke Dennis M.
Published: April 2011

Previous work suggests that gibberellins (GAs) play an important role in early seed development. To more fully understand the roles of GAs throughout seed development, tissue-specific transcription profiles of GA metabolism genes and quantitative profiles of key GAs were determined in pea (Pisum sativum) seeds during the seed-filling development period (8–20 d after anthesis [DAA]). These profiles were correlated with seed photoassimilate acquisition and storage as well as morphological development. Seed coat growth (8–12 DAA) and the subsequent dramatic expansion of branched parenchyma cells were correlated with both transcript abundance of GA biosynthesis genes and the concentration of the growth effector GA, GA1. These results suggest GA1 involvement in determining the rate of seed coat growth and sink strength. The endosperm’s PsGA20ox transcript abundance and the concentration of GA20 increased markedly as the endosperm reached its maximum volume (12 DAA), thus providing ample GA20 substrate for the GA 3-oxidases present in both the embryo and seed coat. Furthermore, PsGA3ox transcript profiles and trends in GA1 levels in embryos at 10 to 16 DAA and also in embryo axes at 18 DAA suggest localized GA1-induced growth in these tissues. A shift from synthesis of GA1 to that of GA8 occurred after 18 DAA in the embryo axis, suggesting that deactivation of GA1 to GA8 is a likely mechanism to limit embryo axis growth and allow embryo maturation to proceed. We hypothesize that GA biosynthesis and catabolism are tightly regulated to bring about the unique developmental events that occur during seed growth, development, and maturation.
A simplified empirical model for approximation of the `bond valence–bond length' correlation for H—O bonds
Authors: Sidey Vasyl
Published: April 2011

The `bond valence (s)–bond length (r)' correlation reported earlier for H—O bonds [Brown (2009). Chem. Rev.
109, 6858–6919] has been closely approximated using the function s = (α − βr)1/γ, where α = 1.185 (10), β = 0.321 (8) and γ = 0.36.
Amino acid changes in P3, and not the overlapping pipo‐encoded protein, determine virulence of Soybean mosaic virus on functionally immune Rsv1‐genotype soybean
Authors: WEN R‐H. , MAROOF M. A. SAGHAI , HAJIMORAD M. R.
Published: April 2011

A small open reading frame, termed ‘pipo’, is embedded in the P3 cistron of potyviruses. Currently, knowledge on pipo and its role(s) in the life cycle of potyviruses is limited. The P3 and helper‐component proteinase (HC‐Pro) cistrons of Soybean mosaic virus (SMV) harbour determinants affecting virulence on functionally immune Rsv1‐genotype soybeans. Interestingly, a key virulence determinant of SMV on Rsv1‐genotype soybeans (i.e. soybeans containing the Rsv1 resistance gene) that resides at polyprotein codon 947 overlaps both P3 and a pipo‐encoded codon. This raises the question of whether PIPO or P3 is the virulence factor. To answer this question, the corresponding pipo of an avirulent and two virulent strains of SMV were studied by comparative genomics, followed by syntheses and analyses of site‐directed mutants. Our data demonstrate that the virulence of SMV on Rsv1‐genotype soybeans is affected by P3 and not the overlapping pipo‐encoded protein.
New perspectives in stem cell research: beyond embryonic stem cells
Authors: Leeb C. , Jurga M. , McGuckin C. , Forraz N. , Thallinger C. , Moriggl R. , Kenner L.
Published: April 2011

Although stem cell research is a rather new field in modern medicine, media soon popularized it. The reason for this hype lies in the potential of stem cells to drastically increase quality of life through repairing aging and diseased organs. Nevertheless, the essence of stem cell research is to understand how tissues are maintained during adult life. In this article, we summarize the various types of stem cells and their differentiation potential in vivo and in vitro. We review current clinical applications of stem cells and highlight problems encountered when going from animal studies to clinical practice. Furthermore, we describe the current state of induced pluripotent stem cell technology and applications for disease modelling and cell replacement therapy.
Insights into the biology of cord blood stem/progenitor cells
Authors: Broxmeyer H. E.
Published: April 2011

Objectives:  To review information on cord blood banking and transplantation with respect to the author’s studies, and in context of this field of investigation.

Results:  Cord blood transplantation has been successfully used to treat a number of malignant and non‐malignant disorders. However, this technique is still associated with limited numbers of cells for transplantation, and with delayed engraftment of neutrophils and platelets. The field of cord blood transplantation will benefit from enhanced and mechanistically based information on haematopoietic stem cell function and potential means to enhance its effectiveness are reviewed. This includes notions concerning possibility of retrieving more cells from the placenta and cord blood, to expand haematopoietic stem cells ex vivo and to increase efficiency of homing and engraftment of these cells. Also discussed are cryopreservation and long‐term storage of cord blood haematopoietic and progenitor cells, and new laboratory findings and animal studies for non‐haematopoietic uses of cord blood.
Social work practitioners' experience of the clinical utility of the Home Observation for Measurement of the Environment (HOME) Inventory
Authors: Glad Johan , Jergeby Ulla , Gustafsson Carina , Sonnander Karin
Published: April 2011

Clinical utility of an assessment instrument can provide important information about the potential value of that instrument when used in practice. The aim of this study was to describe social work practitioners' experiences of the clinical utility of a Swedish version of the Home Observation for Measurement of the Environment (HOME) Inventory. Because knowledge of clinical utility in this area is scarce, a qualitative method based on semi‐structured interviews was used to gain a deeper understanding of the phenomenon. Data were collected through 16 interviews and then analysed by qualitative manifest content analysis. The analysis yielded five categories: improves quality of child protection investigations, supports practitioners, HOME has drawbacks and difficulties, certain issues are important for future applications and basic conditions are crucial. The findings supported the clinical utility of the HOME Inventory though some critical issues have to be addressed, especially concerning the category basic conditions are crucial. A thorough education, the possibility to practice activities related to the administration of the method and support from management were found to be essential. Replication and further studies are needed in the Swedish context to confirm the applicability of the HOME Inventory.
Umbilical cord plasma 25‐hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study
Authors: Chi A. , Wildfire J. , McLoughlin R. , Wood R. A. , Bloomberg G. R. , Kattan M. , Gergen P. , Gold D. R. , Witter F. , Chen T. , Holick M. , Visness C. , Gern J. , O'Connor G. T.
Published: April 2011

Cite this as: A. Chi, J. Wildfire, R. McLoughlin, R. A. Wood, G. R. Bloomberg, M. Kattan, P. Gergen, D. R. Gold, F. Witter, T. Chen, M. Holick, C. Visness, J. Gern and G. T. O'Connor, Clinical & Experimental Allergy, 2011 (41) 842–850.

Background
Recent studies have reported conflicting data on the association between maternal intake of vitamin D during pregnancy and asthma.

Objective
To assess the influence of prenatal vitamin D status on immune function at birth.

Methods
In an inner‐city birth cohort of 568 newborns, 520 of whom had at least one atopic parent, we measured the umbilical cord (UC) plasma concentration of 25‐hydroxyvitamin D (25(OH)D) and the cytokine responses of UC blood mononuclear cells (UCMCs) to stimuli including phytohaemagglutinin (PHA), lipopolysaccharide (LPS), and peptidoglycan. In a subset, the UCMC expression of regulatory T cell markers and the suppressive activity of CD4+CD25+UCMCs were measured.

Results
The 25th, 50th, and 75th percentiles of UC plasma 25(OH)D level were 15.0, 20.2, and 25.6 ng/mL, respectively. Most cytokine responses of UCMC were not correlated with UC 25(OH)D concentration; however, IFN‐γ release after LPS stimulation was weakly positively correlated with UC 25(OH)D concentration (r=0.11, P=0.01). PHA responses were not significantly correlated with 25(OH)D concentration. The UC plasma 25(OH)D concentration was inversely related to the number of CD25+ (r=−0.20, P=0.06), CD25Bright (r=−0.21, P=0.05), and CD25+FoxP3 (r=−0.29, P=0.06) cells as a proportion of CD4+ T cells in UC blood (r=−0.26, P=0.04) but not to the suppressive activity of CD4+CD25+cells (r=0.17, P=0.22).

Conclusion and Clinical Relevance
UC 25(OH)D concentration was not correlated with most UCMC cytokine responses to multiple stimuli. There was a suggestion of a weakly positive correlation with IFN‐γ release after LPS stimulation. The proportions of CD25+, CD25Bright, and CD25+FoxP3 cells to total CD4+ T cells were inversely correlated with UC 25(OH)D concentration. Our findings suggest that higher vitamin D levels at birth may be associated with a lower number of T‐regulatory cells. Vitamin D status in utero may influence immune regulation in early life.
An efficient maximum entropy approach for categorical variable prediction
Authors: Allard D. , D'Or D. , Froidevaux R.
Published: April 2011

We address the problem of the prediction of a spatial categorical variable by revisiting the maximum entropy approach. We first argue that, for predicting category probabilities, a maximum entropy approach is more natural than a least‐squares approach, such as (co‐)kriging of indicator functions. We then show that, knowing the categories observed at surrounding locations, the conditional probability of observing a category at a location obtained with a particular maximum entropy principle is a simple combination of sums and products of univariate and bivariate probabilities. This prediction equation can be used for categorical estimation or categorical simulation. We make connections to earlier work on prediction of categorical variables. On simulated data sets we show that our equation is a very good approximation to Bayesian maximum entropy (BME), while being orders of magnitude faster to compute. Our approach is then illustrated by using the celebrated Swiss Jura data set.
Non‐melanocytic mimics of melanocytic neoplasms
Authors: Bhawan Jag
Published: April 2011

Bhawan J  (2012) Histopathology 60, 715–730 Non‐melanocytic mimics of melanocytic neoplasms

On histopathologic examination, many non‐neoplastic conditions mimic benign or malignant neoplasms. Alternatively, some benign and malignant neoplasms can also mimic non‐neoplastic lesions. This is true of all organ systemsskin is no exception. Examples of these mimickers can be found in skin lesions of almost all tissue types, including those that are melanocytic, lymphoid, epithelial, neural, vascular, neuroendocrine, and fibrohistiocytic. Melanocytic neoplasms are particularly important as it’s challenging to differentiate them as being benign or malignant, and it’s difficult to tell them apart from non‐melanocytic neoplasms. This review illustrates examples of non‐melanocytic lesions that disguise themselves as melanocytic.
Expression hierarchy in the Yersinia type III secretion system established through YopD recognition of RNA
Authors: Chen Yuqing , Anderson Deborah M.
Published: April 2011

The Yersinia type III secretion system (T3SS) is environmentally responsive to enable its rapid induction upon contact with host cells and is necessary for Yersiniae to establish a replicative niche and cause disease. YopD, a translocator protein, represses the expression of T3SS genes until signalled by environmental cues, a mechanism known as the low calcium response. In this work, we investigated recognition of target genes by Yersinia pestis YopD. Expression of all genes of the T3SS was induced in a yopD mutant, though not to the same degree, with effector Yops most affected. Two, short AU‐rich sequence elements up‐ and downstream of start codons of target genes were necessary but not sufficient for YopD mediated repression. Purified YopD–LcrH bound specifically to target RNAs in vitro with different relative affinities, with effector Yops having greater affinity. Together, the data suggest YopD binds to T3SS transcripts where it may prevent ribosome binding causing accelerated mRNA degradation. This regulatory mechanism may ensure an expression hierarchy during the low calcium response as low affinity YopD targets such as chaperones would be translated prior to high affinity targets such as effector Yops allowing the bacteria another layer of control over Yop translocation during infection.
The distribution of E‐cadherin expression in listeric rhombencephalitis of ruminants indicates its involvement inListeria monocytogenesneuroinvasion
Authors: Madarame H. , Seuberlich T. , Abril C. , Zurbriggen A. , Vandevelde M. , Oevermann A.
Published: April 2011

H. Madarame, T. Seuberlich, C. Abril, A. Zurbriggen, M. Vandevelde and A. Oevermann (2011)Neuropathology and Applied Neurobiology37,753–767

The distribution of E‐cadherin expression in listeric rhombencephalitis of ruminants indicates its involvement inListeria monocytogenesneuroinvasion

Aim:To investigate the expression of E‐cadherin, a major host cell receptor forListeria monocytogenes(LM) internalin A, in the ruminant nervous system and its putative role in brainstem invasion and intracerebral spread of LM in the natural disease.Methods:Immunohistochemistry and double immunofluorescence was performed on brains, cranial nerves and ganglia of ruminants with and without natural LM rhombencephalitis using antibodies against E‐cadherin, protein gene product 9.5, myelin‐associated glycoprotein and LM.Results:In the ruminant brain, E‐cadherin is expressed in choroid plexus epithelium, meningothelium and restricted neuropil areas of the medulla, but not in the endothelium. In cranial nerves and ganglia, E‐cadherin is expressed in satellite cells and myelinating Schwann cells. Expression does not differ between ruminants with or without listeriosis and does not overlap with the presence of microabscesses in the medulla. LM is observed in phagocytes, axons, Schwann cells, satellite cells and ganglionic neurones.Conclusion:Our results support the view that the specific ligand–receptor interaction between LM and host E‐cadherin is involved in the neuropathogenesis of ruminant listeriosis. They suggest that oral epithelium and Schwann cells expressing E‐cadherin provide a port of entry for free bacteria offering a site of primary intracellular replication, from where the bacterium may invade the axonal compartment by cell‐to‐cell spread. As E‐cadherin expression in the ruminant central nervous system is weak, only very locally restricted and not related to the presence of microabscesses, it is likely that further intracerebral spread is independent of E‐cadherin and relies primarily on axonal spread.
Clustered lot quality assurance sampling: a pragmatic tool for timely assessment of vaccination coverage
Authors: Greenland K. , Rondy M. , Chevez A. , Sadozai N. , Gasasira A. , Abanida E. A. , Pate M. A. , Ronveaux O. , Okayasu H. , Pedalino B. , Pezzoli L.
Published: April 2011

Objectives  To evaluate oral poliovirus vaccine (OPV) coverage of the November 2009 round in five Northern Nigeria states with ongoing wild poliovirus transmission using clustered lot quality assurance sampling (CLQAS).

Methods  We selected four local government areas in each pre‐selected state and sampled six clusters of 10 children in each Local Government Area, defined as the lot area. We used three decision thresholds to classify OPV coverage: 75–90%, 55–70% and 35–50%. A full lot was completed, but we also assessed in retrospect the potential time‐saving benefits of stopping sampling when a lot had been classified.

Results  We accepted two local government areas (LGAs) with vaccination coverage above 75%. Of the remaining 18 rejected LGAs, 11 also failed to reach 70% coverage, of which four also failed to reach 50%. The average time taken to complete a lot was 10 h. By stopping sampling when a decision was reached, we could have classified lots in 5.3, 7.7 and 7.3 h on average at the 90%, 70% and 50% coverage targets, respectively.

Conclusions  Clustered lot quality assurance sampling was feasible and useful to estimate OPV coverage in Northern Nigeria. The multi‐threshold approach provided useful information on the variation of IPD vaccination coverage. CLQAS is a very timely tool, allowing corrective actions to be directly taken in insufficiently covered areas.
Spatial and temporal clusters of Barmah Forest virus disease in Queensland, Australia
Authors: Naish S. , Hu W. , Mengersen K. , Tong S.
Published: April 2011

Objective  To identify the spatial and temporal clusters of Barmah Forest virus (BFV) disease in Queensland in Australia, using geographical information systems and spatial scan statistic (SaTScan).

Methods  We obtained BFV disease cases, population and statistical local areas (SLAs) boundary data from Queensland Health and Australian Bureau of Statistics, respectively, during 1992–2008 for Queensland. A retrospective Poisson‐based analysis using SaTScan software and method was conducted to identify both purely spatial and space‐time BFV disease high‐rate clusters. A spatial cluster size of a proportion of the population and a 200 km radius and varying time windows from 1 to 12 months were chosen (for the space‐time analysis).

Results  The spatial scan statistic detected a most likely significant purely spatial cluster (including 23 SLAs) and a most likely significant space‐time cluster (including 24 SLAs) in approximately the same location. Significant secondary clusters were also identified from both the analyses in several locations.

Conclusions  This study provides evidence of the existence of statistically significant BFV disease clusters in Queensland, Australia. The study also demonstrated the relevance and applicability of SaTScan in analysing ongoing surveillance data to identify clusters to facilitate the development of effective BFV disease prevention and control strategies in Queensland, Australia.
Development and characterization of microsatellite markers for caladiums (Caladium Vent.)
Authors: Gong LI , Deng Zhanao
Published: April 2011

With 1 table

Microsatellite markers are needed for distinguishing cultivars and mapping disease and pest resistance genes in caladiums, one of the most important ornamental aroids. Through sequencing of a GA‐enriched partial genomic library, 173 unique sequences suitable for designing simple sequence repeat primers were identified. A majority of the sequences (82.7%) contained perfect repeats of GA/TC motif, and 86.8% of the primers amplified discrete PCR products of expected sizes, resulting in development of the first 99 microsatellite markers in caladiums. These markers detected differences at 41.8% and 68.8% of the amplified alleles between two pairs of caladium cultivars that are most difficult to distinguish morphologically. The markers revealed high percentages (70.0% to 78.2%) of polymorphic alleles among three parents of segregating populations to be used for mapping genes for resistance to three major diseases/pests. High rates of transferability (51.7–100%) were observed across seven Caladium species. The availability of these highly polymorphic, robust markers will provide a powerful tool for differentiating cultivars, anchoring genetic maps and understanding the genetic relationships in caladiums.
Impact of grandmultiparity on obstetric outcome in low resource setting
Authors: Agrawal Smriti , Agarwal Anjoo , Das Vinita
Published: April 2011

Aim:  This study was undertaken to evaluate the impact of grandmultiparity on obstetric outcome in a low resource setting.

Material & Methods:  Two hundred and eighty‐two antenatal grandmultiparous women (parity ≥ 4) were compared with consecutive 564 antenatal women with parity 1–3.

Results:  There were 13 403 deliveries over the study period from Jan 2006–December 2008 at CSMMU, Lucknow. The prevalence of grandmultipara was 2.3%. Grandmultipara were older (P < 0.001) and more commonly from rural areas (P < 0.001) as compared to the control group. The percentage of Muslims among grandmultipara (23.8%) was higher than among controls (16.5%), P < 0.01. Grandmultipara had significantly higher prevalence of anemia (P < 0.001), malpresentation (P = 0.01) and rupture uterus (P < 0.001). Abruptio placenta, placenta previa and obstructed labor were seen more often in grandmultipara, and the difference was statistically significant (P < 0.01 in each group). There was no difference in terms of mode of delivery, sex of newborn or the prevalence of low birthweight (<2.5 kg) babies. Stillbirths were more common in grandmultiparas (P < 0.001). There was one maternal death in the study group.

Conclusion:  Grandmultiparity continues to be of grave concern with an adverse impact on obstetric and perinatal outcome.
A case report of fatal tumor lysis syndrome after chemotherapy in a pregnant patient with Burkitt's lymphoma
Authors: Serikawa Takehiro , Abe Takashi , Minamikawa Takahiro , Itsukaichi Mina , Yamada Kyoko , Saito Tomoko , Kaneko Takayuki , Wada Masaki , Takakuwa Koichi , Tanaka Kenichi
Published: April 2011

A 35‐year‐old Japanese woman in the 24th week of gestation with bilateral breast enlargement was referred to hospital. She was diagnosed with Burkitt's lymphoma and admitted for detailed evaluation and treatment. Early delivery and subsequent chemotherapy was chosen after considering the gestational week, her general condition and the wishes of the patient and her husband. She gave birth to a male infant by cesarean section in the 25th week of gestation. It had been planned to begin high‐dose chemotherapy, such as CODOX‐M/IVAC, on day 7 of the puerperium; however, her general condition worsened and chemotherapy was therefore begun on day 2 after the birth. Eight hours after chemotherapy (cyclophosphamide, vincristine and doxorubicin), she developed cardiac arrest due to tumor lysis syndrome. Despite medical treatment, her bleeding tendency did not improve and she died of respiratory failure with alveolar bleeding five days after chemotherapy.
International Outsourcing and the Sector Bias: New Empirical Evidence
Authors: Horgos Daniel
Published: April 2011

Considering labor market effects of international outsourcing on more disaggregated industry levels, a sector bias appears showing that low skilled labor receives a wage premium when international outsourcing takes place in low skill‐intensive industries. However, there is no empirical evidence supporting this pattern. Applying a panel data analysis for Germany, this paper provides new empirical evidence for the existence of the sector bias of international outsourcing: significant results confirm the decreasing wage gap if international outsourcing takes place in low skill‐intensive industries. If international outsourcing takes place in high skill‐intensive industries, the wage gap increases.
Bilateral Trade Agreements and the Feasibility of Multilateral Free Trade
Authors: Saggi Kamal , Yildiz Halis Murat
Published: April 2011

We studied how the pursuit of bilateral free‐trade agreements (FTAs) affects the likelihood of achieving multilateral free trade. We derive and compare the stable Nash equilibria of two games of trade liberalization: in the FTA game, each country can either form an FTA with one of its trading partners or both of them or none of them, whereas in the (restricted) No FTA game, purely bilateral FTAs are not permitted. The major result is that there exist circumstances under which the freedom to pursue (discriminatory) bilateral FTAs is necessary for achieving multilateral free trade.
Affective modulation of the LPP and α‐ERD during picture viewing
Authors: De Cesarei Andrea , Codispoti Maurizio
Published: April 2011

Brain responses to engaging stimuli may be reflected both in event‐related potentials (ERPs) and in electroencephalogram (EEG) oscillations. Previous studies investigating the effects of top‐down factors on stimulus encoding revealed similar modulation of late ERPs and alpha‐band desynchronization (α‐ERD) by relevant target stimuli. Focusing on the bottom‐up effects of emotional content and picture size, the present study aimed to investigate the relationship of the late positive potential (LPP) and α‐ERD during the viewing of emotional pictures. Results showed similar affective modulation by picture arousal of the LPP and α‐ERD. Moreover, picture size reduction diminished overall magnitude of both responses, but did not dampen affective modulation of either response. These results suggest that, during affective picture viewing, these two brain responses similarly reflect the engagement of motivational systems in order to facilitate perception.
Protective effects of lycorine against carbon tetrachloride induced hepatotoxicity in Swiss albino mice
Authors: Ilavenil S. , Kaleeswaran B. , Ravikumar S.
Published: April 2011

Carbon tetrachloride (CCl4) is a well‐known model for inducing chemical hepatic injury in Swiss albino mice. The present study was designed to examine the ability of lycorine a natural alkaloid compound to prevent CCl4‐induced hepatotoxicity in the Swiss albino mice. After the experimental period of 8 weeks, CCl4 significantly increased the generation of lipid peroxidation products, it reflected by high levels of malondialdehyde, hepatic marker enzymes like aspartate transaminase, Alanine transaminase, Lactate dehydrogenase, alkaline phosphatase and lipids profiles. These increases were accompanied by significant decreases of glutathione (GSH); vitamin C content and significant reduction in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione‐S‐transferase and GSH reductase were observed in the mice liver, which were normalized by the lycorine treatment as compared with CCl4‐induced group of mice. Moreover, the histological and ultrastructural observations evidenced that lycorine effectively rescues the hepatocyte from CCl4‐induced oxidative damage without disturbing its cellular metabolic function and structural integrity. Therefore, lycorine may be considered a potent antioxidant against free radical‐related diseases.
Animal models to guide clinical drug development in ADHD: lost in translation?
Authors: Wickens Jeffery R , Hyland Brian I , Tripp Gail
Published: April 2011

We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention‐deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open‐field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6‐hydroxydopamine‐lesioned (6‐OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6‐OHDA‐lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future.

LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways
Authors: Gomez O , Sanchez‐Rodriguez A , Le MQU , Sanchez‐Caro C , Molina‐Holgado F , Molina‐Holgado E
Published: April 2011

BACKGROUND AND PURPOSE The endogenous cannabinoid system participates in oligodendrocyte progenitor differentiation in vitro. To determine the effect of synthetic cannabinoids on oligodendrocyte differentiation, we exposed differentiating cultures of oligodendrocytes with cannabinoid CB1, CB2 and CB1/CB2 receptor agonists and antagonists. The response of the PI3K/Akt and the mammalian target of rapamycin (mTOR) signalling pathways were studied as effectors of cannabinoid activity.

EXPERIMENTAL APPROACH Purified oligodendrocyte progenitor cells (OPC) obtained from primary mixed glial cell cultures were treated for 48 h with CB1, CB2 and CB1/CB2 receptor agonists (ACEA, JWH133 and HU210, respectively) in the presence or absence of the antagonists AM281 (CB1 receptor) and AM630 (CB2 receptor). Moreover, inhibitors of the phosphatidylinositol 3‐kinase (PI3K)/Akt and mTOR pathways (LY294002 and rapamycin, respectively) were used to study the involvement of these pathways on cannabinoid‐induced OPC maturation.

KEY RESULTS ACEA, JWH133 and HU‐210 enhanced OPC differentiation as assessed by the expression of stage specific antigens and myelin basic protein (MBP). Moreover, this effect was blocked by the CB receptor antagonists. ACEA, JWH133 and HU210 induced a time‐dependent phosphorylation of Akt and mTOR, whereas the inhibitors of PI3K/Akt (LY294002) or of mTOR (rapamycin) reversed the effects of HU‐210 on oligodendrocyte differentiation and kinase activation.

CONCLUSIONS AND IMPLICATIONS Activation of cannabinoid CB1 or CB2 receptors with selective agonists accelerated oligodendrocyte differentiation through the mTOR and Akt signalling pathways.

LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Non‐invasive in vivo imaging for liver tumour progression using an orthotopic hepatocellular carcinoma model in immunocompetent mice
Authors: Wang Qin , Luan Wei , Goz Vadim , Burakoff Steven J. , Hiotis Spiros P.
Published: April 2011

Background: Maintenance of complex transgenic colonies and labour‐intensive techniques pose significant challenges in work involving mouse models for hepatocellular carcinoma (HCC). Other animal models of unusual species are generally impractical for research purposes.

Aims: To develop a highly reproducible orthotopic mouse model for HCC based on the murine α‐foetoprotein (AFP), producing cell line Hepa1‐6 and to monitor liver tumour progression via in vivo imaging, and measurement of plasma AFP.

Methods: Intrahepatic tumour was induced following subcapsular implantation of 10+6 Hepa1‐6 cells into C57L/J mice. AFP production was examined in vitro and in vivo using immunoblotting. Three confirmatory non‐invasive imaging modalities were applied to follow tumour progression over time including ultrasound biomicroscopy (UBM), micromagnetic resonance imaging (microMRI), and bioluminescence.

Results: α‐foetoprotein expression was confirmed both in vitro and in vivo, with increasing levels in the plasma as tumours progressed. UBM, microMRI and bioluminescence detected intrahepatic tumours to a 2 mm resolution by day 14. Sequential imaging studies demonstrated an intrahepatic pattern of disease progression with an observed median survival of 29 days. Immunosuppression of tumour‐bearing mice led to a greater tumour size and decreased survival.

Conclusions: Intrahepatic implantation of Hepa1‐6 as a mouse model for HCC is a highly reproducible in vivo system with tumour biology analogous to human disease and is regulated by the presence of an intact host immune system. Tumour progression may be monitored in vivo by UBM, microMRI and bioluminescence. Plasma AFP increases over time, allowing redundancy in non‐invasive means of following tumour progression.
The critical care nurse's role in End‐of‐Life care: issues and challenges
Authors: Efstathiou Nikolaos , Clifford Collette
Published: April 2011

Aim: The purpose of this article is to discuss the challenges critical care nurses face when looking after patients needing End‐of‐Life (EoL) care in critical care environments.

Background: Critical care nurses frequently provide care to patients who fail to respond to treatments offered to support and prolong life. The dying phase for individuals in critical care settings, commonly after withholding/withdrawing treatment, is very short posing great demands on critical care nurses to provide physical and emotional support to both patients and their families. Despite the existence of recognized care planning frameworks that may help nurses in providing EoL care, these are not used by all units and many nurses rely on experience to inform practice. A number of aspects such as communication, patient/family‐centred decision‐making, continuity of care, emotional/spiritual support and support for health professionals have been indicated as contributing factors towards the provision of effective EoL care. These are considered from the perspective of critical care nursing.

Conclusion: Skills development in key aspects of care provision may improve the provision of EoL care for critical care patients and their families.

Relevance to clinical practice: Critical care nurses have an essential role in the provision of effective EoL care; however, this dimension of their role needs further exploration. It is noted that educational opportunities need to be provided for critical care nurses to increase the knowledge on planning and delivering EoL care. To inform this evaluation of current EoL care provision in critical care is necessary to address a knowledge deficit of the needs of nurses who seek to support patients and their families at a critical time.
‘The patient is my space’: hermeneutic investigation of the nurse‐patient relationship in critical care
Authors: Vouzavali Foteini JD , Papathanassoglou Elizabeth DE , Karanikola Maria NK , Koutroubas Anna , Patiraki Elisabeth I , Papadatou Danai
Published: April 2011

Background: The nurse‐patient relationship has been postulated to lie at the core of nursing care. However, it is unclear how this concept applies in critical care, as a great majority of critically ill patients are unable to communicate.

Aims: Through a phenomenological hermeneutical perspective, we aimed to explore intensive care nurses' perceptions and meanings regarding their interpersonal relationship with critically ill individuals.

Methods: A Heideggerian hermeneutical approach was used to design the study and analyse the data, which were collected through repetitive interviews with 12 intensive care nurses.

Results: Critical care nurses report to experience deep relationships with patients, which seem to be mediated by the ongoing contact with patients' bodies. These relationships evoke intense feelings of love, empathy and care and affect how nurses perceive and make sense of their role and their world. The identified core theme of their experience is entitled ‘syncytium’, which describes a network of closely connected cells. According to participants' perceptions, nurse and patient affect each other reciprocally and are mutually dependent upon each other. In Heideggerian terms patients provide nurses with opportunities to experience ‘authentic care’ and they participate in their ‘being‐in‐the‐world’, thus they are central in nurses' meanings about their role and existence. Other elicited themes that account for the perceived nurse‐patient relationship include the spatiality/temporality of the relationship, nurses' perceptions and meanings attributed to their role and nurses' perceptions of death.

Conclusions: Critical care nurses appear to experience their relationships with patients intensely. These relationships are invested with meanings and elicit powerful feelings over a shared course with patients. Patients are central in nurses' meaning‐making process and role perception.

Relevance to clinical practice: These findings have implications for the educational preparation of critical care nurses and their psychological support.
The Risks of High Ultrafiltration Rate in Chronic Hemodialysis: Implications for Patient Care
Authors: Flythe Jennifer E. , Brunelli Steven M.
Published: April 2011

As dialytic practice has evolved, hemodialysis (HD) adequacy has come to be defined in terms of small molecule clearance. A growing body of evidence suggests that fluid dynamics, specifically ultrafiltration rate (UFR), bear clinical and physiological significance and should perhaps play a more central role in titrating HD therapy. Three recent studies have shown an independent association between higher UFR and mortality. Further work is needed to determine whether this relationship represents a direct toxic effect of rapid fluid perturbations or whether this association is a consequence of confounding on the basis of large interdialytic weight gain, as each would prompt a different therapeutic response. This mounting evidence builds the case that fluid management should play a more central role in the dialytic prescription and that more individualized approaches to fluid management should be encouraged.