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Find video protocols related to scientific articles indexed in Pubmed.
Work-related musculoskeletal disorders in nursing: current knowledge and ongoing challenges for occupational health.
Med Lav
PUBLISHED: 07-15-2014
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Work-related Musculoskeletal Disorders (MSD) represent a major occupational health concern when considering the relationships between work and disease but associations between MSD and hospital work, especially in the nursing profession, aren't yet full understanded.QMSDuestions that still need to be answered include: Are nurses' work-related musculoskeletal symptoms and injuries dependent on the wards, the hospital organization and even the national occupational health policies that they originated from? Is their MSD related with workplaces demands, equipment, and nurse-patient ratios? Do these factors highlight different nursing occupational exposure to MSD hazards? What are the individual and psychosocial contributes to nurses WRMSDs in different nursing contexts? As such, a new approach which integrates more realistic working conditions, real hospital equipment, workplace features, and individual information would likely be a better way forwards in the addressing the current MSD epidemic among hospital nurses, worldwide......
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Antigenic variation of clade 2.1 H5N1 virus is determined by a few amino acid substitutions immediately adjacent to the receptor binding site.
MBio
PUBLISHED: 06-12-2014
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Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. Antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about the antigenic evolution of HPAI H5N1 viruses that circulate in poultry. In this study, we focused on HPAI H5N1 viruses that are enzootic to Indonesia. We selected representative viruses from genetically distinct lineages that are currently circulating and determined their antigenic properties by hemagglutination inhibition assays. At least six antigenic variants have circulated between 2003, when H5N1 clade 2.1 viruses were first detected in Indonesia, and 2011. During this period, multiple antigenic variants cocirculated in the same geographic regions. Mutant viruses were constructed by site-directed mutagenesis to represent each of the circulating antigenic variants, revealing that antigenic differences between clade 2.1 viruses were due to only one or very few amino acid substitutions immediately adjacent to the receptor binding site. Antigenic variants of H5N1 virus evaded recognition by both ferret and chicken antibodies. The molecular basis for antigenic change in clade 2.1 viruses closely resembled that of seasonal human influenza viruses, indicating that the hemagglutinin of influenza viruses from different hosts and subtypes may be similarly restricted to evade antibody recognition.
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Low back pain among school teachers in Botswana, prevalence and risk factors.
BMC Musculoskelet Disord
PUBLISHED: 05-13-2014
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Although low back pain (LBP) represents a common occupational problem, few epidemiological studies have investigated the prevalence and risk factors for LBP among school teachers, particularly in Africa. School teachers are known to represent an occupational group among which there appears to be a high prevalence of LBP. The objective of this study was, therefore, to conduct one of the first epidemiological investigations of LBP among teachers in Botswana.
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Excessive production and extreme editing of human metapneumovirus defective interfering RNA is associated with type I IFN induction.
J. Gen. Virol.
PUBLISHED: 04-23-2014
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Type I IFN production is one of the hallmarks of host innate immune responses upon virus infection. Whilst most respiratory viruses carry IFN antagonists, reports on human metapneumovirus (HMPV) have been conflicting. Using deep sequencing, we have demonstrated that HMPV particles accumulate excessive amounts of defective interfering RNA (DIs) rapidly upon in vitro passage, and that these are associated with IFN induction. Importantly, the DIs were edited extensively; up to 70% of the original A and T residues had mutated to G or C, respectively. Such high editing rates of viral RNA have not, to our knowledge, been reported before. Bioinformatics and PCR assays indicated that adenosine deaminase acting on RNA (ADAR) was the most likely editing enzyme. HMPV thus has an unusually high propensity to generate DIs, which are edited at an unprecedented high frequency. The conflicting published data on HMPV IFN induction and antagonism are probably explained by DIs in virus stocks. The interaction of HMPV DIs with the RNA-editing machinery and IFN responses warrants further investigation.
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Sedimentation and the reproductive biology of the Hawaiian reef-building coral Montipora capitata.
Biol. Bull.
PUBLISHED: 03-21-2014
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Environmental conditions can influence the physiology of marine organisms and have important implications for their reproductive performance and capacity to supply new recruits. This study examined the seasonal reproductive patterns of the coral Montipora capitata in habitats exposed to different sedimentation regimes. Although M. capitata is a main reef-building coral in the Hawaiian Archipelago, little is known about the gametogenic cycle and reproductive ecology of this important species. Our results indicate that gamete production in M. capitata is a resilient process; no differences in gamete development or fecundity were observed among sites with very different sedimentation regimes. The gametogenic cycle of M. capitata lasts between 10 and 11 months, with spawning occurring over 3-5 months during warmer months (May-September). Oocytes were found throughout the year, but spermatocysts were only found April-August. The largest increases in oocyte size occurred during February to May, the months when solar radiation increased rapidly. The largest variation in oocyte sizes was found during July and August; during this period individual colonies contained mature oocytes for immediate spawning and new oocytes being formed for spawning the next year. The capacity of M. capitata to reproduce in areas with high sedimentation is an interesting finding highlighting the potential of the species for acclimatization, adaptation, or both. Despite this optimistic finding, the management of terrestrial runoff and the restoration of habitat quality for corals remains a top priority to ensure the renewal and maintenance of coral populations.
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Musculoskeletal disorders in a 3 year longitudinal cohort of dental hygiene students.
J Dent Hyg
PUBLISHED: 02-25-2014
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Musculoskeletal disorders (MSDs) are a significant occupational health issue for the dental hygiene profession. There is increasing evidence that these problems commence during undergraduate training; however, there is a surprising lack of studies investigating how MSD develops in student groups over the course of their study. The aim of this study was to determine the longitudinal MSD trends among a cohort of undergraduate dental hygiene students at an Australian university.
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Integrating influenza antigenic dynamics with molecular evolution.
Elife
PUBLISHED: 02-06-2014
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Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001.
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Unifying viral genetics and human transportation data to predict the global transmission dynamics of human influenza H3N2.
PLoS Pathog.
PUBLISHED: 02-01-2014
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Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control.
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Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential.
Cell Host Microbe
PUBLISHED: 01-30-2014
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Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited pathogenicity in mice and ferrets higher than that in an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential.
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WHO recommendations for the viruses used in the 2013-2014 Northern Hemisphere influenza vaccine: Epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013.
Vaccine
PUBLISHED: 01-28-2014
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In February the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winter in the Northern Hemisphere. These recommendations are based on data collected by National Influenza Centres (NICs) through the WHO Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations of the 2013-2014 Northern Hemisphere influenza vaccine composition.
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PeptidePicker: a scientific workflow with web interface for selecting appropriate peptides for targeted proteomics experiments.
J Proteomics
PUBLISHED: 01-16-2014
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One challenge in Multiple Reaction Monitoring (MRM)-based proteomics is to select the most appropriate surrogate peptides to represent a target protein. We present here a software package to automatically generate these most appropriate surrogate peptides for an LC/MRM-MS analysis. Our method integrates information about the proteins, their tryptic peptides, and the suitability of these peptides for MRM which is available online in UniProtKB, NCBI's dbSNP, ExPASy, PeptideAtlas, PRIDE, and GPMDB. The scoring algorithm reflects our knowledge in choosing the best candidate peptides for MRM, based on the uniqueness of the peptide in the targeted proteome, its physiochemical properties, and whether it previously has been observed. The modularity of the workflow allows further extension and additional selection criteria to be incorporated. We have developed a simple Web interface where the researcher provides the protein accession number, the subject organism, and peptide-specific options. Currently, the software is designed for human and mouse proteomes, but additional species can be easily be added. Our software improved the peptide selection by eliminating human error, considering multiple data sources and all of the isoforms of the protein, and resulted in faster peptide selection - approximately 50 proteins per hour compared to 8 per day.
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The application of multiple reaction monitoring and multi-analyte profiling to HDL proteins.
Lipids Health Dis
PUBLISHED: 01-08-2014
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HDL carries a rich protein cargo and examining HDL protein composition promises to improve our understanding of its functions. Conventional mass spectrometry methods can be lengthy and difficult to extend to large populations. In addition, without prior enrichment of the sample, the ability of these methods to detect low abundance proteins is limited. Our objective was to develop a high-throughput approach to examine HDL protein composition applicable to diabetes and cardiovascular disease (CVD).
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A Recommended Numbering Scheme for Influenza A HA Subtypes.
PLoS ONE
PUBLISHED: 01-01-2014
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Comparisons of residues between sub-types of influenza virus is increasingly used to assess the zoonotic potential of a circulating strain and for comparative studies across subtypes. An analysis of N-terminal cleavage sites for thirteen subtypes of influenza A hemagglutinin (HA) sequences, has previously been described by Nobusawa and colleagues. We have expanded this analysis for the eighteen known subtypes of influenza. Due to differences in the length of HA, we have included strains from multiple clades of H1 and H5, as well as strains of H5 and H7 subtypes with both high and low pathogenicity. Analysis of known structures of influenza A HA enables us to define amino acids which are structurally and functionally equivalent across all HA subtypes using a numbering system based on the mature HA sequence. We provide a list of equivalences for amino acids which are known to affect the phenotype of the virus.
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A transparent and transferable framework for tracking quality information in large datasets.
PLoS ONE
PUBLISHED: 01-01-2014
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The ability to evaluate the validity of data is essential to any investigation, and manual "eyes on" assessments of data quality have dominated in the past. Yet, as the size of collected data continues to increase, so does the effort required to assess their quality. This challenge is of particular concern for networks that automate their data collection, and has resulted in the automation of many quality assurance and quality control analyses. Unfortunately, the interpretation of the resulting data quality flags can become quite challenging with large data sets. We have developed a framework to summarize data quality information and facilitate interpretation by the user. Our framework consists of first compiling data quality information and then presenting it through 2 separate mechanisms; a quality report and a quality summary. The quality report presents the results of specific quality analyses as they relate to individual observations, while the quality summary takes a spatial or temporal aggregate of each quality analysis and provides a summary of the results. Included in the quality summary is a final quality flag, which further condenses data quality information to assess whether a data product is valid or not. This framework has the added flexibility to allow "eyes on" information on data quality to be incorporated for many data types. Furthermore, this framework can aid problem tracking and resolution, should sensor or system malfunctions arise.
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Identification of a Pantoea biosynthetic cluster that directs the synthesis of an antimicrobial natural product.
PLoS ONE
PUBLISHED: 01-01-2014
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Fire Blight is a destructive disease of apple and pear caused by the enteric bacterial pathogen, Erwinia amylovora. E. amylovora initiates infection by colonizing the stigmata of apple and pear trees, and entering the plants through natural openings. Epiphytic populations of the related enteric bacterium, Pantoea, reduce the incidence of disease through competition and antibiotic production. In this study, we identify an antibiotic from Pantoea ananatis BRT175, which is effective against E. amylovora and select species of Pantoea. We used transposon mutagenesis to create a mutant library, screened approximately 5,000 mutants for loss of antibiotic production, and recovered 29 mutants. Sequencing of the transposon insertion sites of these mutants revealed multiple independent disruptions of an 8.2 kb cluster consisting of seven genes, which appear to be coregulated. An analysis of the distribution of this cluster revealed that it was not present in any other of our 115 Pantoea isolates, or in any of the fully sequenced Pantoea genomes, and is most closely related to antibiotic biosynthetic clusters found in three different species of Pseudomonas. This identification of this biosynthetic cluster highlights the diversity of natural products produced by Pantoea.
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Sociodemographic factors and prejudice toward HIV and hepatitis B/C status in a working-age population: results from a national, cross-sectional study in Japan.
PLoS ONE
PUBLISHED: 01-01-2014
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In many countries, HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infected individuals may face discrimination and mistreatment from coworkers. Effective interventions to reduce workplace discrimination are therefore needed to protect these vulnerable populations. The current study investigated potential associations between sociodemographic factors and prejudice toward HIV and HBV/HCV infected colleagues within a Japanese working population.
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Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling.
Front Neurosci
PUBLISHED: 01-01-2014
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Neural stem cells (NSCs) are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates bone morphogenetic protein (BMP)-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP) and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.
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Genome-wide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011.
J. Virol.
PUBLISHED: 12-26-2013
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Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. The viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update the influenza vaccine frequently. Using two datasets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that the influenza A(H3N2) virus evolution could be mapped into thirteen antigenic clusters. Here, we have analyzed the full genome of 286 influenza A(H3N2) viruses from these two datasets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events, scattered over the entire period of virus circulation, were found, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Further, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitution were most pronounced for hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1 and non-structural protein 1. This study of genotype in relation to the antigenic phenotype throughout the entire period of circulation of human influenza A(H3N2) viruses leads to a better understanding of its evolution.
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Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution.
Science
PUBLISHED: 11-23-2013
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The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.
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Draft Genome Sequence of the Antibiotic-Producing Epiphytic Isolate Pantoea ananatis BRT175.
Genome Announc
PUBLISHED: 11-09-2013
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Pantoea is a member of the Enterobacteriaceae, whose members have been shown to produce novel antibiotics. Here, we report the 4.8-Mb genome sequence of Pantoea ananatis strain BRT175, an epiphytic isolate from strawberries that produces an antibiotic that is effective against the fire blight pathogen, Erwinia amylovora.
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Draft Genome Sequence of the Antibiotic-Producing Cystic Fibrosis Isolate Pantoea agglomerans Tx10.
Genome Announc
PUBLISHED: 11-02-2013
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Pantoea agglomerans is an enteric bacterium that is capable of causing both plant and human disease. Here, we report the genome sequence of a cystic fibrosis isolate, P. agglomerans Tx10, which produces an antibiotic that is effective against Staphylococcus aureus.
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Guide to the assessment of physical activity: Clinical and research applications: a scientific statement from the American Heart Association.
Circulation
PUBLISHED: 10-14-2013
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The deleterious health consequences of physical inactivity are vast, and they are of paramount clinical and research importance. Risk identification, benchmarks, efficacy, and evaluation of physical activity behavior change initiatives for clinicians and researchers all require a clear understanding of how to assess physical activity. In the present report, we have provided a clear rationale for the importance of assessing physical activity levels, and we have documented key concepts in understanding the different dimensions, domains, and terminology associated with physical activity measurement. The assessment methods presented allow for a greater understanding of the vast number of options available to clinicians and researchers when trying to assess physical activity levels in their patients or participants. The primary outcome desired is the main determining factor in the choice of physical activity assessment method. In combination with issues of feasibility/practicality, the availability of resources, and administration considerations, the desired outcome guides the choice of an appropriate assessment tool. The decision matrix, along with the accompanying tables, provides a mechanism for this selection that takes all of these factors into account. Clearly, the assessment method adopted and implemented will vary depending on circumstances, because there is no single best instrument appropriate for every situation. In summary, physical activity assessment should be considered a vital health measure that is tracked regularly over time. All other major modifiable cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, obesity, and smoking) are assessed routinely. Physical activity status should also be assessed regularly. Multiple physical activity assessment methods provide reasonably accurate outcome measures, with choices dependent on setting-specific resources and constraints. The present scientific statement provides a guide to allow professionals to make a goal-specific selection of a meaningful physical activity assessment method.
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Toxicokinetic, Toxicodynamic, and Toxicoproteomic Aspects of Short-term Exposure to Trenbolone in Female Fish.
Toxicol. Sci.
PUBLISHED: 09-26-2013
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The toxicokinetics of trenbolone was characterized during 500ng/l water exposures in female rainbow trout (Oncorhynchus mykiss) and fathead minnows (Pimephales promelas). Related experiments measured various toxicodynamic effects of exposure. In both species, trenbolone was rapidly absorbed from the water and reached peak plasma levels within 8h of exposure. Afterwards, trenbolone concentrations in trout (66-95ng/ml) were 2-6 times higher compared with minnows (15-29ng/ml), which was attributable to greater plasma binding in trout. During water exposures, circulating levels of estradiol (E2) rapidly decreased in both species to a concentration that was 25%-40% of control values by 8-24h of exposure and then remained relatively unchanged for the subsequent 6 days of exposure. In trout, changes in circulating levels of follicle-stimulating hormone were also significantly greater after trenbolone exposure, relative to controls. In both species, the pharmacokinetics of injected E2-d3 was altered by trenbolone exposure with an increase in total body clearance and a corresponding decrease in elimination half-life. The unbound percentage of E2 in trout plasma was 0.25%, which was similar in pre- or postvitellogenic female trout. Subsequent incubation with trenbolone caused the unbound percentage to significantly increase to 2.4% in the previtellogenic trout plasma. iTRAQ-based toxicoproteomic studies in minnows exposed to 5, 50, and 500ng/l trenbolone identified a total of 148 proteins with 19 downregulated including vitellogenin and 18 upregulated. Other downregulated proteins were fibrinogens, ?-2-macroglobulin, and transferrin. Upregulated proteins included amine oxidase, apolipoproteins, parvalbumin, complement system proteins, and several uncharacterized proteins. The results indicate trenbolone exposure is a highly dynamic process in female fish with uptake and tissue equilibrium quickly established, leading to both rapid and delayed toxicodynamic effects.
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Prevalence of tobacco smoking among school teachers in Botswana.
Tob Induc Dis
PUBLISHED: 09-18-2013
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Tobacco is a leading cause of death worldwide, and nearly 80% of all smokers live in low to middle income countries. Previous research has suggested that smoking rates vary by occupation, with relatively low rates commonly seen among educators. Despite this fact, little is known about the smoking habits of teachers in Botswana. The objective of this study, therefore, was to investigate prevalence and correlates of tobacco use among school teachers in Botswana.
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Tobacco use among Australian dental hygiene students is declining, but more still needs to be done.
Tob Induc Dis
PUBLISHED: 09-11-2013
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While health care professionals have a responsibility to prevent and control the use of tobacco for improved health outcomes, it appears that some dental hygiene students continue to smoke. A survey of Australian dental hygiene students found that up to 16.3% smoke, although this prevalence rate decreased with each year of study. As future role models, it is essential that smoking cessation counselling is embedded in the dental curriculum to not only discourage their own habits, but so that they may promote the importance of being tobacco free to the wider population.
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Gain-of-Function Experiments on H7N9.
Science
PUBLISHED: 08-09-2013
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Since the end of March 2013, avian a influenza viruses of the H7N9 subtype have caused more than 130 human cases of infection in China, many of which were severe, resulting in 43 fatalities. Although this A(H7N9) virus outbreak is now under control, the virus (or one with similar properties) could reemerge as winter approaches. To better assess the pandemic threat posed by A(H7N9) viruses, NIAID/NIH Centers of Excellence in Influenza Research and Surveillance (CEIRS) investigators and other expert laboratories in China and elsewhere have characterized the wild-type avian A(H7N9) viruses in terms of host range, virulence, and transmission, and are evaluating the effectiveness of antiviral drugs and vaccine candidates. However, to fully assess the potential risk associated with these novel viruses, there is a need for additional research including experiments that may be classified as "gain-of-function" (GOF). Here, we outline the aspects of the current situation that most urgently require additional research, our proposed studies, and risk-mitigation strategies.
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Cochrane re-arranged: support for policies to vaccinate elderly people against influenza.
Vaccine
PUBLISHED: 07-16-2013
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The 2010 Cochrane review on efficacy, effectiveness and safety of influenza vaccination in the elderly by Jefferson et al. covering dozens of clinical studies over a period of four decades, confirmed vaccine safety, but found no convincing evidence for vaccine effectiveness (VE) against disease thus challenging the ongoing efforts to vaccinate the elderly. However, the Cochrane review analyzed and presented the data in a way that may itself have hampered the desired separation of real vaccine benefits from inevitable background noise. The data are arranged in more than one hundred stand-alone meta-analyses, according to various vaccine types, study designs, populations, and outcome case definitions, and then further subdivided according to virus circulation and antigenic match. In this way, general vaccine effects could not be separated from an abundance of environmental and operational, non vaccine-related variation. Furthermore, expected impacts of changing virus circulation and antigenic drift on VE could not be demonstrated. We re-arranged the very same data according to a biological and conceptual framework based on the basic sequence of events throughout the patient journey (exposure, infection, clinical outcome, observation) and using broad outcome definitions and simple frequency distributions of VE values. This approach produced meaningful predictions for VE against influenza-related fatal and non-fatal complications (average ~30% with large dispersion), typical influenza-like illness (~40%), disease with confirmed virus infection (~50%), and biological vaccine efficacy against infection (~60%), under conditions of virus circulation. We could also demonstrate a VE average around zero in the absence of virus circulation, and decreasing VE values with decreasing virus circulation and increasing antigenic drift. We regard these findings as substantial evidence for the ability of influenza vaccine to reduce the risk of influenza infection and influenza-related disease and death in the elderly.
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Hepatitis Screening in Japanese Individuals of Working Age and Prejudice against Infected Persons in the Workplace.
J Occup Health
PUBLISHED: 06-28-2013
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Background: Laboratory confirmation of viral hepatitis infection represents an important issue for working age populations, as early detection and treatment can help ameliorate clinical progression of the disease. On the other hand, prejudice may occur in the workplace against those identified by a positive hepatitis test. This study investigated attitudes towards viral hepatitis testing in Japanese people of working age, including their desire to undergo such testing, and prejudice against persons infected with hepatitis virus. Methods: A total of 3,129 working age individuals were recruited from a company that conducts Internet surveys in Japan. Results: Of the respondents, 21.3% had previously undergone viral hepatitis testing, most frequently when it was an additional option during a health checkup or health screening (36.2%) and when it was included in regular health checkups in their workplace (19.2%). Among the respondents with no history of testing, 68.7% expressed a desire to undergo testing, of whom 74.8% wanted to have the test as part of their regular health checkups in the workplace. According to the respondents, if a coworker tested positive for hepatitis, 36.0% reported that they would be anxious about it, 32.0% would try to avoid contact with the infected person as long as circumstances permitted, and 23.7% said they might harbor some kind of bias. Conclusions: Although further promotion of viral hepatitis testing is needed and this might be achieved during regular health checkups in Japanese workplaces, educational strategies will also be essential to help reduce bias against those who test positive.
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Limited airborne transmission of H7N9 influenza A virus between ferrets.
Nature
PUBLISHED: 06-06-2013
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Wild waterfowl form the main reservoir of influenza A viruses, from which transmission occurs directly or indirectly to various secondary hosts, including humans. Direct avian-to-human transmission has been observed for viruses of subtypes A(H5N1), A(H7N2), A(H7N3), A(H7N7), A(H9N2) and A(H10N7) upon human exposure to poultry, but a lack of sustained human-to-human transmission has prevented these viruses from causing new pandemics. Recently, avian A(H7N9) viruses were transmitted to humans, causing severe respiratory disease and deaths in China. Because transmission via respiratory droplets and aerosols (hereafter referred to as airborne transmission) is the main route for efficient transmission between humans, it is important to gain an insight into airborne transmission of the A(H7N9) virus. Here we show that although the A/Anhui/1/2013 A(H7N9) virus harbours determinants associated with human adaptation and transmissibility between mammals, its airborne transmissibility in ferrets is limited, and it is intermediate between that of typical human and avian influenza viruses. Multiple A(H7N9) virus genetic variants were transmitted. Upon ferret passage, variants with higher avian receptor binding, higher pH of fusion, and lower thermostability were selected, potentially resulting in reduced transmissibility. This A(H7N9) virus outbreak highlights the need for increased understanding of the determinants of efficient airborne transmission of avian influenza viruses between mammals.
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Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS).
Mol. Cell Proteomics
PUBLISHED: 05-20-2013
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Multiple reaction monitoring (MRM) mass spectrometry coupled with stable isotope dilution (SID) and liquid chromatography (LC) is increasingly used in biological and clinical studies for precise and reproducible quantification of peptides and proteins in complex sample matrices. Robust LC-SID-MRM-MS-based assays that can be replicated across laboratories and ultimately in clinical laboratory settings require standardized protocols to demonstrate that the analysis platforms are performing adequately. We developed a system suitability protocol (SSP), which employs a predigested mixture of six proteins, to facilitate performance evaluation of LC-SID-MRM-MS instrument platforms, configured with nanoflow-LC systems interfaced to triple quadrupole mass spectrometers. The SSP was designed for use with low multiplex analyses as well as high multiplex approaches when software-driven scheduling of data acquisition is required. Performance was assessed by monitoring of a range of chromatographic and mass spectrometric metrics including peak width, chromatographic resolution, peak capacity, and the variability in peak area and analyte retention time (RT) stability. The SSP, which was evaluated in 11 laboratories on a total of 15 different instruments, enabled early diagnoses of LC and MS anomalies that indicated suboptimal LC-MRM-MS performance. The observed range in variation of each of the metrics scrutinized serves to define the criteria for optimized LC-SID-MRM-MS platforms for routine use, with pass/fail criteria for system suitability performance measures defined as peak area coefficient of variation <0.15, peak width coefficient of variation <0.15, standard deviation of RT <0.15 min (9 s), and the RT drift <0.5min (30 s). The deleterious effect of a marginally performing LC-SID-MRM-MS system on the limit of quantification (LOQ) in targeted quantitative assays illustrates the use and need for a SSP to establish robust and reliable system performance. Use of a SSP helps to ensure that analyte quantification measurements can be replicated with good precision within and across multiple laboratories and should facilitate more widespread use of MRM-MS technology by the basic biomedical and clinical laboratory research communities.
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In vivo reprogramming of astrocytes to neuroblasts in the adult brain.
Nat. Cell Biol.
PUBLISHED: 05-13-2013
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Adult differentiated cells can be reprogrammed into pluripotent stem cells or lineage-restricted proliferating precursors in culture; however, this has not been demonstrated in vivo. Here, we show that the single transcription factor SOX2 is sufficient to reprogram resident astrocytes into proliferative neuroblasts in the adult mouse brain. These induced adult neuroblasts (iANBs) persist for months and can be generated even in aged brains. When supplied with BDNF and noggin or when the mice are treated with a histone deacetylase inhibitor, iANBs develop into electrophysiologically mature neurons, which functionally integrate into the local neural network. Our results demonstrate that adult astrocytes exhibit remarkable plasticity in vivo, a feature that might have important implications in regeneration of the central nervous system using endogenous patient-specific glial cells.
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Elevated glucocorticoids during ovine pregnancy increase appetite and produce glucose dysregulation and adiposity in their granddaughters in response to ad libitum feeding at 1 year of age.
Am. J. Obstet. Gynecol.
PUBLISHED: 05-03-2013
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Synthetic glucocorticoids (sGCs) are administered to women threatening preterm labor. We have shown multigenerational endocrine and metabolic effects of fetal sGC exposure. We hypothesized that sGC exposure would alter the second filial generation (F2) offspring neonatal leptin peak that controls development of appetitive behavior with metabolic consequences.
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Dimensions and reliability of a hospital safety climate questionnaire in Chinese health-care practice.
Int J Nurs Pract
PUBLISHED: 04-13-2013
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The aim of the current study was to examine the dimensions and reliability of a hospital safety climate questionnaire in Chinese health-care practice. To achieve this, a cross-sectional survey of health-care professionals was undertaken at a university teaching hospital in Shandong province, China. Our survey instrument demonstrated very high internal consistency, comparing well with previous research in this field conducted in other countries. Factor analysis highlighted four key dimensions of safety climate, which centred on employee personal protection, employee interactions, safety-related housekeeping and time pressures. Overall, this study suggests that hospital safety climate represents an important aspect of health-care practice in contemporary China.
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Computational biomarker pipeline from discovery to clinical implementation: plasma proteomic biomarkers for cardiac transplantation.
PLoS Comput. Biol.
PUBLISHED: 04-01-2013
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Recent technical advances in the field of quantitative proteomics have stimulated a large number of biomarker discovery studies of various diseases, providing avenues for new treatments and diagnostics. However, inherent challenges have limited the successful translation of candidate biomarkers into clinical use, thus highlighting the need for a robust analytical methodology to transition from biomarker discovery to clinical implementation. We have developed an end-to-end computational proteomic pipeline for biomarkers studies. At the discovery stage, the pipeline emphasizes different aspects of experimental design, appropriate statistical methodologies, and quality assessment of results. At the validation stage, the pipeline focuses on the migration of the results to a platform appropriate for external validation, and the development of a classifier score based on corroborated protein biomarkers. At the last stage towards clinical implementation, the main aims are to develop and validate an assay suitable for clinical deployment, and to calibrate the biomarker classifier using the developed assay. The proposed pipeline was applied to a biomarker study in cardiac transplantation aimed at developing a minimally invasive clinical test to monitor acute rejection. Starting with an untargeted screening of the human plasma proteome, five candidate biomarker proteins were identified. Rejection-regulated proteins reflect cellular and humoral immune responses, acute phase inflammatory pathways, and lipid metabolism biological processes. A multiplex multiple reaction monitoring mass-spectrometry (MRM-MS) assay was developed for the five candidate biomarkers and validated by enzyme-linked immune-sorbent (ELISA) and immunonephelometric assays (INA). A classifier score based on corroborated proteins demonstrated that the developed MRM-MS assay provides an appropriate methodology for an external validation, which is still in progress. Plasma proteomic biomarkers of acute cardiac rejection may offer a relevant post-transplant monitoring tool to effectively guide clinical care. The proposed computational pipeline is highly applicable to a wide range of biomarker proteomic studies.
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Managing Generation Y occupational therapists: optimising their potential.
Aust Occup Ther J
PUBLISHED: 03-14-2013
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Generation Y is a descriptor of those therapists born between 1982 and 2000. According to generational theory, each generation have unique characteristics due to the social and historical factors they have experienced during their formative years. Occupational therapy educators have reported on Generation Y characteristics observed in occupational therapy students. This study aimed to investigate if managers considered there was a Generation Y therapist and their observed characteristics in practice, as well as successful management strategies used to maximise their potential in the workplace.
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Musculoskeletal disorders and symptom severity among Australian dental hygienists.
BMC Res Notes
PUBLISHED: 02-15-2013
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Recent literature has identified that musculoskeletal disorders (MSD) are a significant occupational health issue for both dentists and dental hygienists. Research on the occupational health of dental hygienists is lacking in Australia, which is of particular concern given that it is a rapidly growing field in this country. The aims of this research are to investigate the prevalence of MSD and correlating regions of pain among Australian dental hygienists. A self-reporting questionnaire was distributed to all registered dental hygienists in Australia. The questionnaire was a modified version of a validated tool, used previously among health practitioners and students.
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Influenza vaccination uptake among the working age population of Japan: results from a national cross-sectional survey.
PLoS ONE
PUBLISHED: 02-13-2013
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Influenza vaccination rates among Japanese people of working age (20-69 years) is currently suboptimal, and the reasons for this have not been clearly elucidated. This study examined factors associated with vaccination intention among the working age population in Japan during September 2011, one-month prior to influenza vaccination becoming available.
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Avian influenza virus surveillance in wild birds in Georgia: 2009-2011.
PLoS ONE
PUBLISHED: 02-05-2013
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The Caucasus, at the border of Europe and Asia, is important for migration and over-wintering of wild waterbirds. Three flyways, the Central Asian, East Africa-West Asia, and Mediterranean/Black Sea flyways, converge in the Caucasus region. Thus, the Caucasus region might act as a migratory bridge for influenza virus transmission when birds aggregate in high concentrations in the post-breeding, migrating and overwintering periods. Since August 2009, we have established a surveillance network for influenza viruses in wild birds, using five sample areas geographically spread throughout suitable habitats in both eastern and western Georgia. We took paired tracheal and cloacal swabs and fresh feces samples. We collected 8343 swabs from 76 species belonging to 17 families in 11 orders of birds, of which 84 were real-time RT-PCR positive for avian influenza virus (AIV). No highly pathogenic AIV (HPAIV) H5 or H7 viruses were detected. The overall AIV prevalence was 1.6%. We observed peak prevalence in large gulls during the autumn migration (5.3-9.8%), but peak prevalence in Black-headed Gulls in spring (4.2-13%). In ducks, we observed increased AIV prevalence during the autumn post-moult aggregations and migration stop-over period (6.3%) but at lower levels to those observed in other more northerly post-moult areas in Eurasia. We observed another prevalence peak in the overwintering period (0.14-5.9%). Serological and virological monitoring of a breeding colony of Armenian Gulls showed that adult birds were seropositive on arrival at the breeding colony, but juveniles remained serologically and virologically negative for AIV throughout their time on the breeding grounds, in contrast to gull AIV data from other geographic regions. We show that close phylogenetic relatives of viruses isolated in Georgia are sourced from a wide geographic area throughout Western and Central Eurasia, and from areas that are represented by multiple different flyways, likely linking different host sub-populations.
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The impact of Generation Y occupational therapy students on practice education.
Aust Occup Ther J
PUBLISHED: 12-28-2011
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Many occupational therapy students can be classified as Generation Y, a group whose characteristics are perceived as being confident, optimistic and techno-savvy. This study aimed to explore practice educator perceptions of Generation Y students.
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Interlaboratory evaluation of automated, multiplexed peptide immunoaffinity enrichment coupled to multiple reaction monitoring mass spectrometry for quantifying proteins in plasma.
Mol. Cell Proteomics
PUBLISHED: 12-22-2011
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The inability to quantify large numbers of proteins in tissues and biofluids with high precision, sensitivity, and throughput is a major bottleneck in biomarker studies. We previously demonstrated that coupling immunoaffinity enrichment using anti-peptide antibodies (SISCAPA) to multiple reaction monitoring mass spectrometry (MRM-MS) produces Immunoprecipitation MRM-MS (immuno-MRM-MS) assays that can be multiplexed to quantify proteins in plasma with high sensitivity, specificity, and precision. Here we report the first systematic evaluation of the interlaboratory performance of multiplexed (8-plex) immuno-MRM-MS in three independent labs. A staged study was carried out in which the effect of each processing and analysis step on assay coefficient of variance, limit of detection, limit of quantification, and recovery was evaluated. Limits of detection were at or below 1 ng/ml for the assayed proteins in 30 ?l of plasma. Assay reproducibility was acceptable for verification studies, with median intra- and interlaboratory coefficients of variance above the limit of quantification of 11% and <14%, respectively, for the entire immuno-MRM-MS assay process, including enzymatic digestion of plasma. Trypsin digestion and its requisite sample handling contributed the most to assay variability and reduced the recovery of target peptides from digested proteins. Using a stable isotope-labeled protein as an internal standard instead of stable isotope-labeled peptides to account for losses in the digestion process nearly doubled assay accuracy for this while improving assay precision 5%. Our results demonstrate that multiplexed immuno-MRM-MS can be made reproducible across independent laboratories and has the potential to be adopted widely for assaying proteins in matrices as complex as plasma.
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Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-05-2011
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Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.
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Bibliometric awareness in nursing scholarship: can we afford to ignore it any longer?
Nurs Health Sci
PUBLISHED: 11-20-2011
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In contemporary nursing academia, it is unthinkable that topics such as research methods, evidence-based practice, and the translation of research into practice would be omitted from nursing curricula at any level. What is surprising, however, is that despite a broad educational emphasis on "teaching research", the rising importance of bibliometrics appears to have been largely neglected. If nursing scholarship and nursing scholars are to prosper in the highly competitive field of modern health research, a sophisticated understanding of citation-based methods is clearly required. Armed with this knowledge, one can more successfully argue why scarce research funding, that might otherwise be channeled elsewhere, ought to be assigned to nursing researchers. We hereby urge readers to reflect on the extent to which bibliometrics is covered within formal nursing curricula at their college or university. It is no longer a case of if a graduate nurse will need this skill set for their future professional development, but when.
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A systematic review of musculoskeletal disorders among school teachers.
BMC Musculoskelet Disord
PUBLISHED: 09-13-2011
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Musculoskeletal disorders (MSD) represent one of the most common and most expensive occupational health problems in both developed and developing countries. School teachers represent an occupational group among which there appears to be a high prevalence of MSD. Given that causes of MSD have been described as multi-factorial and prevalence rates vary between body sites and location of study, the objective of this systematic review was to investigate the prevalence and risk factors for MSD among teaching staff.
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Flavivirus-induced antibody cross-reactivity.
J. Gen. Virol.
PUBLISHED: 09-07-2011
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Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae.
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Occupational stress and psychosomatic complaints among health professionals in Beijing, China.
Work
PUBLISHED: 08-31-2011
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To investigate the prevalence, distribution and correlates of occupationally-related psychosomatic complaints among a previously understudied workforce. Participants: A selection of 336 public health professionals working in Beijing, China.
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Evolution of re-emergent virus and its impact on enterovirus 71 epidemics.
Exp. Biol. Med. (Maywood)
PUBLISHED: 06-29-2011
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Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, has become an emergent infectious disease worldwide, most notably in Asia. As a neurotropic virus, EV71 infection occasionally causes neurological diseases with pulmonary edema, which is fatal for children. In this review, we examine the epidemiology of EV71, with three waves of increased EV71 activity since the 1970s and discuss the genotypic changes in phylogeny between the outbreaks or epidemics. Genetic changes including mutations and recombinations as well as the diversity of antigenic properties among EV71 strains in various outbreaks are described. Furthermore, the impact of genetic changes on viral pathogenesis and vaccine candidate selection are addressed. In conclusion, these genetic and antigenic investigations of EV71 evolution have provided us with new insight into the trend of EV71 epidemiology, which may contribute to a better understanding of the viral pathogenesis and vaccine development.
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Examining the dimensions of hospital safety climate and psychosocial risk factors among Japanese nurses.
J Transcult Nurs
PUBLISHED: 04-25-2011
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The purpose of this study was to examine the dimensions, reliability, and main loading factors associated with a Japanese safety climate and psychosocial risk factor scale.
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H7 avian influenza virus vaccines protect chickens against challenge with antigenically diverse isolates.
Vaccine
PUBLISHED: 04-12-2011
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Vaccination has been a critical tool in the control of some avian influenza viruses (AIV) and has been used routinely in Pakistan to help control sporadic outbreaks of highly pathogenic (HP) H7 AIV since 1995. During that time, several AIV isolates were utilized as inactivated vaccines with varying degrees of success. In order to evaluate which H7 AIV strains may serve as optimal vaccines for diverse H7 AIVs from Pakistan we conducted vaccination-challenge studies with five H7 vaccines against challenge with two HPAIVs: A/chicken/Murree/NARC-1/1995 H7N3 and A/chicken/Karachi/SPVC-4/2004 H7N3. To further characterize the isolates antigenic cartography was used to visually demonstrate the antigenic relationships among the isolates. All vaccines provided similar protection against mortality, morbidity and shedding of challenge virus from the respiratory tract. However, some minor (not statistically significant) differences were observed and correlated with antibody levels induced by the vaccine prior to challenge.
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Differential protein expression throughout the life cycle of Trypanosoma congolense, a major parasite of cattle in Africa.
Mol. Biochem. Parasitol.
PUBLISHED: 02-07-2011
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Trypanosoma congolense is an important pathogen of livestock in Africa. To study protein expression throughout the T. congolense life cycle, we used culture-derived parasites of each of the three main insect stages and bloodstream stage parasites isolated from infected mice, to perform differential protein expression analysis. Three complete biological replicates of all four life cycle stages were produced from T. congolense IL3000, a cloned parasite that is amenable to culture of major life cycle stages in vitro. Cellular proteins from each life cycle stage were trypsin digested and the resulting peptides were labeled with isobaric tags for relative and absolute quantification (iTRAQ). The peptides were then analyzed by tandem mass spectrometry (MS/MS). This method was used to identify and relatively quantify proteins from the different life cycle stages in the same experiment. A search of the Wellcome Trusts Sanger Institutes semi-annotated T. congolense database was performed using the MS/MS fragmentation data to identify the corresponding source proteins. A total of 2088 unique protein sequences were identified, representing 23% of the ?9000 proteins predicted for the T. congolense proteome. The 1291 most confidently identified proteins were prioritized for further study. Of these, 784 yielded annotated hits while 501 were described as "hypothetical proteins". Six proteins showed no significant sequence similarity to any known proteins (from any species) and thus represent new, previously uncharacterized T. congolense proteins. Of particular interest among the remainder are several membrane molecules that showed drastic differential expression, including, not surprisingly, the well-studied variant surface glycoproteins (VSGs), invariant surface glycoproteins (ISGs) 65 and 75, congolense epimastigote specific protein (CESP), the surface protease GP63, an amino acid transporter, a pteridine transporter and a haptoglobin-hemoglobin receptor. Several of these surface disposed proteins are of functional interest as they are necessary for survival of the parasites.
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Glucocorticoid receptor stimulation and the regulation of neonatal cerebellar neural progenitor cell apoptosis.
Neurobiol. Dis.
PUBLISHED: 01-04-2011
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Glucocorticoids are used to treat respiratory dysfunction associated with premature birth but have been shown to cause neurodevelopmental deficits when used therapeutically. Recently, we established that acute glucocorticoid exposure at clinically relevant doses produces neural progenitor cell apoptosis in the external granule layer of the developing mouse cerebellum and permanent decreases in the number of cerebellar neurons. As the cerebellum naturally matures and neurogenesis is no longer needed, the external granule layer decreases proliferation and permanently disappears during the second week of life. At this same time, corticosterone (the endogenous rodent glucocorticoid) release increases and a glucocorticoid-metabolizing enzyme that protects the external granule layer against glucocorticoid receptor stimulation (11?-Hydroxysteroid-Dehydrogenase-Type 2; HSD2) naturally disappears. Here we show that HSD2 inhibition and raising corticosterone to adult physiological levels both can independently increase neural progenitor cell apoptosis in the neonatal mouse. Conversely, glucocorticoid receptor antagonism decreases natural physiological apoptosis in this same progenitor cell population suggesting that endogenous glucocorticoid stimulation may regulate apoptosis in the external granule layer. We also found that glucocorticoids which HSD2 can effectively metabolize generate less external granule layer apoptosis than glucocorticoids this enzyme is ineffective at breaking down. This finding may explain why glucocorticoids that this enzyme can metabolize are clinically effective at treating respiratory dysfunction yet seem to produce no neurodevelopmental deficits. Finally, we demonstrate that both acute and chronic glucocorticoid exposures produce external granule layer apoptosis but without appropriate control groups this effect becomes masked. These results are discussed in terms of their implications for glucocorticoid therapy and neurodevelopment during the perinatal period.
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Genetic and antigenic characterization of H1 influenza viruses from United States swine from 2008.
J. Gen. Virol.
PUBLISHED: 12-22-2010
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Prior to the introduction of the 2009 pandemic H1N1 virus from humans into pigs, four phylogenetic clusters (?-, ?-, ?- and ?) of the haemagglutinin (HA) gene from H1 influenza viruses could be found in US swine. Information regarding the antigenic relatedness of the H1 viruses was lacking due to the dynamic and variable nature of swine lineage H1. We characterized 12 H1 isolates from 2008 by using 454 genome-sequencing technology and phylogenetic analysis of all eight gene segments and by serological cross-reactivity in the haemagglutination inhibition (HI) assay. Genetic diversity was demonstrated in all gene segments, but most notably in the HA gene. The gene segments from the 2009 pandemic H1N1 formed clusters separate from North American swine lineage viruses, suggesting progenitors of the pandemic virus were not present in US pigs immediately prior to 2009. Serological cross-reactivity paired with antigenic cartography demonstrated that the viruses in the different phylogenetic clusters are also antigenically divergent.
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An international review of musculoskeletal disorders in the dental hygiene profession.
Int Dent J
PUBLISHED: 12-15-2010
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This review of the current literature is aimed at examining musculoskeletal disorders in dental hygienists, and investigates the complex nature of this significant occupational health issue. Musculoskeletal disorders (MSD) have been identified as a significant issue for the profession of dental hygiene. The purpose of this review is to examine and assemble the best evidence on the epidemiology, diagnosis, treatment, interventions, prevention, impact and consequences of MSD among the dental hygiene profession. The prevalence of MSD is alarming, with up to 96% reporting pain, and a number of occupational risk factors have been identified by the literature. Studies investigating interventions are generally limited in their study design, which is concerning given the huge impact MSD can have on the practising dental hygienist. Overall, it is evident from the literature that MSD is a complex and multifactorial problem. However, a complete understanding of the progression of musculoskeletal disorders is still far from being realised, due to the lack of longitudinal studies and standardised research techniques. Future research should implement triangulation methods in longitudinal studies, a strategy which will go a long way in the understanding of this complex occupational health issue.
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Sport education and extracurricular sport participation: an examination using the trans-contextual model of motivation.
Res Q Exerc Sport
PUBLISHED: 12-08-2010
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In this study, we used the trans-contextual model of motivation (TCM) to examine the effect of Sport Education (SE) on students participation in a voluntary lunch recess sport club. A total of 192 participants (ages 9-14 years) completed measures of the TCM constructs before and after a 12-week SE intervention period. Participants had the opportunity to participate in weekly, voluntary lunch recess sport club sessions during the intervention period. SE elicited a moderate increase in autonomous motives in physical education. The TCM accounted for a significant proportion of the explained variance in lunch recess sport club intention and participation. Autonomy-supportive curricular models, such as SE, may have the potential to facilitate transfer of motivation and participation in physical activity from a physical education to an extracurricular context.
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Identification of Leishmania-specific protein phosphorylation sites by LC-ESI-MS/MS and comparative genomics analyses.
Proteomics
PUBLISHED: 10-21-2010
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Human pathogenic protozoa of the genus Leishmania undergo various developmental transitions during the infectious cycle that are triggered by changes in the host environment. How these parasites sense, transduce, and respond to these signals is only poorly understood. Here we used phosphoproteomic approaches to monitor signaling events in L. donovani axenic amastigotes, which may be important for intracellular parasite survival. LC-ESI-MS/MS analysis of IMAC-enriched phosphoprotein extracts identified 445 putative phosphoproteins in two independent biological experiments. Functional enrichment analysis allowed us to gain insight into parasite pathways that are regulated by protein phosphorylation and revealed significant enrichment in our data set of proteins whose biological functions are associated with protein turn-over, stress response, and signal transduction. LC-ESI-MS/MS analysis of TiO(2)-enriched phosphopeptides confirmed these results and identified 157 unique phosphopeptides covering 181 unique phosphorylation sites in 126 distinct proteins. Investigation of phosphorylation site conservation across related trypanosomatids and higher eukaryotes by multiple sequence alignment and cluster analysis revealed L. donovani-specific phosphoresidues in highly conserved proteins that share significant sequence homology to orthologs of the human host. These unique phosphorylation sites reveal important differences between host and parasite biology and post-translational protein regulation, which may be exploited for the design of novel anti-parasitic interventions.
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Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding.
J. Virol.
PUBLISHED: 09-15-2010
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The clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by reverse genetics, and the effect on virus receptor binding, replication, antigenic properties, and pathogenesis and transmission in animal models was investigated. pdmH1N1 with D222G caused ocular disease in mice without further indications of enhanced virulence in mice and ferrets. pdmH1N1 with D222G retained transmissibility via aerosols or respiratory droplets in ferrets and guinea pigs. The virus displayed changes in attachment to human respiratory tissues in vitro, in particular increased binding to macrophages and type II pneumocytes in the alveoli and to tracheal and bronchial submucosal glands. Virus attachment studies further indicated that pdmH1N1 with D222G acquired dual receptor specificity for complex ?2,3- and ?2,6-linked sialic acids. Molecular dynamics modeling of the hemagglutinin structure provided an explanation for the retention of ?2,6 binding. Altered receptor specificity of the virus with D222G thus affected interaction with cells of the human lower respiratory tract, possibly explaining the observed association with enhanced disease in humans.
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A quantitative study of the effects of chaotropic agents, surfactants, and solvents on the digestion efficiency of human plasma proteins by trypsin.
J. Proteome Res.
PUBLISHED: 08-21-2010
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Plasma biomarkers studies are based on the differential expression of proteins between different treatment groups or between diseased and control populations. Most mass spectrometry-based methods of protein quantitation, however, are based on the detection and quantitation of peptides, not intact proteins. For peptide-based protein quantitation to be accurate, the digestion protocols used in proteomic analyses must be both efficient and reproducible. There have been very few studies, however, where plasma denaturation/digestion protocols have been compared using absolute quantitation methods. In this paper, 14 combinations of heat, solvent [acetonitrile, methanol, trifluoroethanol], chaotropic agents [guanidine hydrochloride, urea], and surfactants [sodium dodecyl sulfate (SDS) and sodium deoxycholate (DOC)] were compared with respect to their effectiveness in improving subsequent tryptic digestion. These digestion protocols were evaluated by quantitating the production of proteotypic tryptic peptides from 45 moderate- to high-abundance plasma proteins, using tandem mass spectrometry in multiple reaction monitoring mode, with a mixture of stable-isotope labeled analogues of these proteotypic peptides as internal standards. When the digestion efficiencies of these 14 methods were compared, we found that both of the surfactants (SDS and DOC) produced an increase in the overall yield of tryptic peptides from these 45 proteins, when compared to the more commonly used urea protocol. SDS, however, can be a serious interference for subsequent mass spectrometry. DOC, on the other hand, can be easily removed from the samples by acid precipitation. Examining the results of a reproducibility study, done with 5 replicate digestions, DOC and SDS with a 9 h digestion time produced the highest average digestion efficiencies (?80%), with the highest average reproducibility (<5% error, defined as the relative deviation from the mean value). However, because of potential interferences resulting from the use of SDS, we recommend DOC with a 9 h digestion procedure as the optimum protocol.
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Use of antigenic cartography in vaccine seed strain selection.
Avian Dis.
PUBLISHED: 06-05-2010
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Human influenza A viruses are classic examples of antigenically variable pathogens that have a seemingly endless capacity to evade the hosts immune response. The viral hemagglutinin (HA) and neuraminidase (NA) proteins are the main targets of our antibody response to combat infections. HA and NA continuously change to escape from humoral immunity, a process known as antigenic drift. As a result of antigenic drift, the human influenza vaccine is updated frequently. The World Health Organization (WHO) coordinates a global influenza surveillance network that, by the hemagglutination inhibition (HI) assay, routinely characterizes the antigenic properties of circulating strains in order to select new seed viruses for such vaccine updates. To facilitate a quantitative interpretation and easy visualization of HI data, a new computational technique called "antigenic cartography" was developed. Since its development, antigenic cartography has been applied routinely to assist the WHO with influenza surveillance activities. Until recently, antigenic variation was not considered a serious issue with influenza vaccines for poultry. However, because of the diversification of the Asian H5N1 lineage since 1996 into multiple genetic clades and subclades, and because of the long-term use of poultry vaccines against H5 in some parts of the world, this issue needs to be re-addressed. The antigenic properties of panels of avian H5N1 viruses were characterized by HI assay, using mammalian or avian antisera, and analyzed using antigenic cartography methods. These analyses revealed antigenic differences between circulating H5N1 viruses and the H5 viruses used in poultry vaccines. Considerable antigenic variation was also observed within and between H5N1 clades. These observations have important implications for the efficacy and long-term use of poultry vaccines.
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Studies needed to address public health challenges of the 2009 H1N1 influenza pandemic: insights from modeling.
PLoS Med.
PUBLISHED: 06-01-2010
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In light of the 2009 influenza pandemic and potential future pandemics, Maria Van Kerkhove and colleagues anticipate six public health challenges and the data needed to support sound public health decision making.
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Establishing national priorities for Australian occupational health and safety research.
J Occup Health
PUBLISHED: 05-06-2010
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This study aimed to identify current and emerging issues relevant to Occupational Health & Safety (OHS) research in Australia, and to formulate strategic research directions and strategies for the future.
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Exploring new frontiers in occupational epidemiology: the Hunter Community Study (HCS) from Australia.
Ind Health
PUBLISHED: 04-29-2010
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This article describes a pioneering longitudinal investigation from Australia known as the Hunter Community Study (HCS). The HCS investigates retired and near-retired persons randomly selected in a regional area on the heavily populated east coast. As it collects detailed survey, clinical, and biological measures, the HCS is more comprehensive than most other research of this nature. The HCS also has significant occupational implications at an international level, being one of the first Australian studies to take a full, lifetime occupational history linked to job exposures. Longitudinal cohort studies with exposure assessment, such as the HCS offer epidemiologists around the world a clear opportunity for examining and evaluating the long-term risks of employment across a variety of workplace settings. It is only with detailed datasets that continuing progress can be made in elucidating mechanisms of occupational disease causation in the new millennium.
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Perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant women.
J. Clin. Endocrinol. Metab.
PUBLISHED: 04-28-2010
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Thyroid hormone, requiring adequate maternal iodine intake, is critical for fetal neurodevelopment. Perchlorate decreases thyroidal iodine uptake by competitively inhibiting the sodium/iodide symporter. It is unclear whether environmental perchlorate exposure adversely affects thyroid function in pregnant women. Thiocyanate, derived from foods and cigarette smoke, is a less potent competitive sodium/iodide symporter inhibitor than perchlorate.
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Different levels of overnutrition and weight gain during pregnancy have differential effects on fetal growth and organ development.
Reprod. Biol. Endocrinol.
PUBLISHED: 03-29-2010
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Nearly 50% of U.S. women of child-bearing age are overweight or obese, conditions linked to offspring obesity and diabetes.
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Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain.
Anesthesiology
PUBLISHED: 03-18-2010
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Brief isoflurane anesthesia induces neuroapoptosis in the developing rodent brain, but susceptibility of non-human primates to the apoptogenic action of isoflurane has not been studied. Therefore, we exposed postnatal day 6 (P6) rhesus macaques to a surgical plane of isoflurane anesthesia for 5 h, and studied the brains 3 h later for histopathologic changes.
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Hospital safety climate, psychosocial risk factors and needlestick injuries in Japan.
Ind Health
PUBLISHED: 02-18-2010
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To investigate the interactions between safety climate, psychosocial issues and Needlestick and Sharps Injuries (NSI), a cross-sectional study was undertaken among nurses at a university teaching hospital in Japan (89% response rate). NSI were correlated with various aspects of hospital safety climate including supporting one another at work, the protection of staff against blood-borne diseases being a high management priority, managers doing their part to protect staff from blood-borne disease, having unsafe work practices corrected by supervisors, having the opportunity to use safety equipment to protect against blood-borne disease exposures, having an uncluttered work area, and having minimal conflict within their department. In conclusion, this study has demonstrated the importance of hospital safety climate in Japanese health care practice, particularly its relationship with NSI. Although the provision of safer devices remains critical in preventing injuries, ensuring a positive safety climate will also be essential in meeting these important challenges for nurses occupational health.
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A longitudinal analysis of bibliometric and impact factor trends among the core international journals of nursing, 1977-2008.
Int J Nurs Stud
PUBLISHED: 01-28-2010
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Although bibliometric analysis affords significant insight into the progression and distribution of information within a particular research field, detailed longitudinal studies of this type are rare within the field of nursing.
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A novel system for the investigation of microvascular dysfunction including vascular permeability and flow-mediated dilatation in pressurised human arteries.
J Pharmacol Toxicol Methods
PUBLISHED: 01-25-2010
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Adverse drug reactions may be manifested through changes in microvascular function (e.g. angioedema) or by subtle modification of the mechanisms controlling vascular tone, such as flow-mediated dilatation. Until now the early detection of such adverse drug reactions has been hampered by the lack of a predictive in vitro model. This in vitro model can be utilised to test potential effect of drugs on the normal responses of the vascular system.
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Why an A-loop phospho-mimetic fails to activate PAK1: understanding an inaccessible kinase state by molecular dynamics simulations.
Structure
PUBLISHED: 01-18-2010
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Crystal structures of inactive PAK1(K299R) and the activation (A)-loop phospho-mimetic PAK1(T423E) have suggested that the kinase domain is in an active state regardless of activation loop status. Contrary to a large body of literature, we find that neither is PAK1(T423E) active in cells, nor does it exhibit significant activity in vitro. To explain these discrepancies all-atom molecular dynamics (MD) simulations of PAK1(phospho-T423) in complex with ATP and substrate were performed. These simulations point to a key interaction between PAK1 Lys308, at the end of the alphaC helix, and the pThr423 phosphate group, not seen in X-ray structures. The orthologous PAK4 Arg359 fulfills the same role in immobilizing the alphaC helix. These in silico predictions were validated by experimental mutagenesis of PAK1 and PAK4. The simulations explain why the PAK1 A-loop phospho-mimetic is inactive, but also point to a key functional interaction likely found in other protein kinases.
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Improved automated analysis of radon (222Rn) and thoron (220Rn) in natural waters.
Environ. Sci. Technol.
PUBLISHED: 12-24-2009
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Natural radon ((222)Rn) and thoron ((220)Rn) can be used as tracers of various chemical and physical processes in the environment. We present here results from an extended series of laboratory experiments intended to improve the automated analysis of (222)Rn and (220)Rn in water using a modified RAD AQUA (Durridge Inc.) system. Previous experience with similar equipment showed that it takes about 30-40 min for the system to equilibrate to radon-in-water concentration increases and even longer for the response to return to baseline after a sharp spike. While the original water/gas exchanger setup was built only for radon-in-water measurement, our goal here is to provide an automated system capable of high resolution and good sensitivity for both radon- and thoron-in-water detections. We found that faster water flow rates substantially improved the response for both isotopes while thoron is detected most efficiently at airflow rates of 3 L/min. Our results show that the optimum conditions for fastest response and sensitivity for both isotopes are at water flow rates up to 17 L/min and an airflow rate of 3 L/min through the detector. Applications for such measurements include prospecting for naturally occurring radioactive material (NORM) in pipelines and locating points of groundwater/surface water interaction.
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A 30-year citation analysis of bibliometric trends at the Archives Of Environmental Health, 1975-2004.
Arch Environ Occup Health
PUBLISHED: 12-17-2009
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This article describes a 30-year citation analysis of the Archives of Environmental Health (AEH), from the earliest available data in 1975, to 2004, when it became the Archives of Environmental & Occupational Health (AEOH). Longitudinal trends were examined regarding the number of items published, the number of citations received, the immediacy index, and the journals impact factor. A list of the 5 most highly cited articles was also established, including citation frequency and citation lag times. Overall, this study demonstrates that citation analysis can provide an interesting look at the development of a journal over time. The examination of what articles, themes, and topics were being published, cited, or ignored also offers a unique insight into the direction of not only a particular journal, but also the discipline within which it exists.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.