bluuebunny/crossref_metadata_2025 huggingface dataset:
Limb Salvage in an Unstable Ankle Fracture of a Diabetic Patient With Charcot Arthropathy
Authors: Johnson Adam R. , Yoon Patrick
Published: May 2010

The treatment of ankle fractures in the presence of diabetes mellitus can be difficult because of a higher complication rate with this subset of the population. When peripheral neuropathy is present at the time of trauma, there is an increased risk of developing Charcot arthropathy, a limb-threatening complication that often creates breakdown, instability, and chronic ulceration of the limb. The authors present a case report of a diabetic patient who sustained an unstable ankle fracture with subsequent neuroarthropathic event that required multiple surgical procedures for salvage of the limb.
Kitted Out for Australia: Dress and Chattels for British Emigrants, 1840–70
Authors: Jarvis Anthea
Published: May 2010

Over 1.5 million men, women and children emigrated from Britain to Australia and New Zealand in the second half of the nineteenth century. This paper explores how they coped with the privations of the voyage, and how they prepared themselves to make the best possible impression in their new country through their clothes.
Mrs Beazley's Kredemnon: Homeric Comforts for the Troops, 1939–45
Authors: Alden Maureen
Published: May 2010

The veil which the White Goddess, Ino, gave to Odysseus to protect him inspired an unorthodox garment sent as a comfort to the troops of the Second World War.
Pediatric mastocytosis–associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KIT-phosphotransferase domain mutations
Authors: Yang Ying , Létard Sébastien , Borge Laurence , Chaix Amandine , Hanssens Katia , Lopez Sophie , Vita Marina , Finetti Pascal , Birnbaum Daniel , Bertucci François , Gomez Sophie , de Sepulveda Paulo , Dubreuil Patrice
Published: May 2010

Compared with adults, pediatric mastocytosis has a relatively favorable prognosis. Interestingly, a difference was also observed in the status of c-kit mutations according to the age of onset. Although most adult patients have a D816V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus KIT-PTD mutants were introduced into rodent Ba/F3, EML, Rat2, and human TF1 cells to investigate their biologic effect. Both ECD and PTD mutations induced constitutive receptor autophosphorylation and ligand-independent proliferation of the 3 hematopoietic cells. Unlike ECD mutants, PTD mutants enhanced cluster formation and up-regulated several mast cell-related antigens in Ba/F3 cells. PTD mutants failed to support colony formation and erythropoietin-mediated erythroid differentiation. ECD and PTD mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT, whereas AKT was only activated by ECD mutants. Consistently, AKT inhibitor suppressed ECD mutant-dependent proliferation, clonogenicity, and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EML-PTD cells, suggesting the differential role of AKT in those mutants. Overall, our study implied different pathogenesis of pediatric versus adult mastocytosis, which might explain their diverse phenotypes.
Building better fibrin knob mimics: an investigation of synthetic fibrin knob peptide structures in solution and their dynamic binding with fibrinogen/fibrin holes
Authors: Stabenfeldt Sarah E. , Gossett J. Jared , Barker Thomas H.
Published: May 2010

Fibrin polymerizes via noncovalent and dynamic association of thrombin-exposed “knobs” with complementary “holes.” Synthetic knob peptides have received significant interest as a means for understanding fibrin assembly mechanisms and inhibiting fibrin polymerization. Nevertheless, the inability to crystallize short peptides significantly limits our understanding of knob peptide structural features that regulate dynamic knob:hole interactions. In this study, we used molecular simulations to generate the first predicted structure(s) of synthetic knobs in solution before fibrin hole engagement. Combining surface plasmon resonance (SPR), we explored the role of structural and electrostatic properties of knob “A” mimics in regulating knob:hole binding kinetics. SPR results showed that association rates were most profoundly affected by the presence of both additional prolines as well as charged residues in the sixth to seventh positions. Importantly, analyzing the structural dynamics of the peptides through simulation indicated that the 3Arg side chain orientation and peptide backbone stability each contribute significantly to functional binding. These findings provide insights into early fibrin protofibril assembly dynamics as well as establishing essential design parameters for high-affinity knob mimics that more efficiently compete for hole occupancy, parameters realized here through a novel knob mimic displaying a 10-fold higher association rate than current mimics.
Sézary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors
Authors: Campbell James J. , Clark Rachael A. , Watanabe Rei , Kupper Thomas S.
Published: May 2010

Cutaneous T-cell lymphoma (CTCL) encompasses leukemic variants (L-CTCL) such as Sézary syndrome (SS) and primarily cutaneous variants such as mycosis fungoides (MF). To clarify the relationship between these clinically disparate presentations, we studied the phenotype of T cells from L-CTCL and MF. Clonal malignant T cells from the blood of L-CTCL patients universally coexpressed the lymph node homing molecules CCR7 and L-selectin as well as the differentiation marker CD27, a phenotype consistent with central memory T cells. CCR4 was also universally expressed at high levels, and there was variable expression of other skin addressins (CCR6, CCR10, and CLA). In contrast, T cells isolated from MF skin lesions lacked CCR7/L-selectin and CD27 but strongly expressed CCR4 and CLA, a phenotype suggestive of skin resident effector memory T cells. Our results suggest that SS is a malignancy of central memory T cells and MF is a malignancy of skin resident effector memory T cells.
The homeobox gene Hhex regulates the earliest stages of definitive hematopoiesis
Authors: Paz Helicia , Lynch Maureen R. , Bogue Clifford W. , Gasson Judith C.
Published: May 2010

The development and emergence of the hematopoietic stem cell involves a series of tightly regulated molecular events that are not well characterized. The hematopoietically expressed homeobox (Hhex) gene, a member of the homeobox gene family, is an essential regulator of embryogenesis and hematopoietic progenitor development. To investigate the role of Hhex in hematopoiesis we adapted a murine embryonic stem (ES) cell coculture system, in which ES cells can differentiate into CD41+ and CD45+ hematopoietic progenitors in vitro. Our results show that in addition to delayed hemangioblast development, Hhex−/− ES-derived progeny accumulate as CD41+ and CD41+c-kit+ cells, or the earliest definitive hematopoietic progenitors. In addition, Hhex−/− ES-derived progeny display a significantly reduced ability to develop into mature CD45+ hematopoietic cells. The observed reduction in hematopoietic maturation was accompanied by reduced proliferation, because Hhex−/− CD41+CD45−c-kit+ hematopoietic progenitors accumulated in the G2 phase of the cell cycle. Thus, Hhex is a critical regulator of hematopoietic development and is necessary for the maturation and proliferation of the earliest definitive hematopoietic progenitors.
CNstream: A method for the identification and genotyping of copy number polymorphisms using Illumina microarrays
Authors: Alonso Arnald , Julià Antonio , Tortosa Raül , Canaleta Cristina , Cañete Juan D , Ballina Javier , Balsa Alejandro , Tornero Jesús , Marsal Sara
Published: May 2010

Background

Understanding the genetic basis of disease risk in depth requires an exhaustive knowledge of the types of genetic variation. Very recently, Copy Number Variants (CNVs) have received much attention because of their potential implication in common disease susceptibility. Copy Number Polymorphisms (CNPs) are of interest as they segregate at an appreciable frequency in the general population (i.e. > 1%) and are potentially implicated in the genetic basis of common diseases.

Results

This paper concerns CNstream, a method for whole-genome CNV discovery and genotyping, using Illumina Beadchip arrays. Compared with other methods, a high level of accuracy was achieved by analyzing the measures of each intensity channel separately and combining information from multiple samples. The CNstream method uses heuristics and parametrical statistics to assign a confidence score to each sample at each probe; the sensitivity of the analysis is increased by jointly calling the copy number state over a set of nearby and consecutive probes. The present method has been tested on a real dataset of 575 samples genotyped using Illumina HumanHap 300 Beadchip, and demonstrates a high correlation with the Database of Genomic Variants (DGV). The same set of samples was analyzed with PennCNV, one of the most frequently used copy number inference methods for Illumina platforms. CNstream was able to identify CNP loci that are not detected by PennCNV and it increased the sensitivity over multiple other loci in the genome.

Conclusions

CNstream is a useful method for the identification and characterization of CNPs using Illumina genotyping microarrays. Compared to the PennCNV method, it has greater sensitivity over multiple CNP loci and allows more powerful statistical analysis in these regions. Therefore, CNstream is a robust CNP analysis tool of use to researchers performing genome-wide association studies (GWAS) on Illumina platforms and aiming to identify CNVs associated with the variables of interest. CNstream has been implemented as an R statistical software package that can work directly from raw intensity files generated from Illumina GWAS projects. The method is available athttp://www.urr.cat/cnv/cnstream.html.
Functional enrichment analyses and construction of functional similarity networks with high confidence function prediction by PFP
Authors: Hawkins Troy , Chitale Meghana , Kihara Daisuke
Published: May 2010

Background

A new paradigm of biological investigation takes advantage of technologies that produce large high throughput datasets, including genome sequences, interactions of proteins, and gene expression. The ability of biologists to analyze and interpret such data relies on functional annotation of the included proteins, but even in highly characterized organisms many proteins can lack the functional evidence necessary to infer their biological relevance.

Results

Here we have applied high confidence function predictions from our automated prediction system, PFP, to three genome sequences, Escherichia coli, Saccharomyces cerevisiae, and Plasmodium falciparum (malaria). The number of annotated genes is increased by PFP to over 90% for all of the genomes. Using the large coverage of the function annotation, we introduced the functional similarity networks which represent the functional space of the proteomes. Four different functional similarity networks are constructed for each proteome, one each by considering similarity in a single Gene Ontology (GO) category, i.e. Biological Process, Cellular Component, and Molecular Function, and another one by considering overall similarity with the funSim score. The functional similarity networks are shown to have higher modularity than the protein-protein interaction network. Moreover, the funSim score network is distinct from the single GO-score networks by showing a higher clustering degree exponent value and thus has a higher tendency to be hierarchical. In addition, examining function assignments to the protein-protein interaction network and local regions of genomes has identified numerous cases where subnetworks or local regions have functionally coherent proteins. These results will help interpreting interactions of proteins and gene orders in a genome. Several examples of both analyses are highlighted.

Conclusion

The analyses demonstrate that applying high confidence predictions from PFP can have a significant impact on a researchers' ability to interpret the immense biological data that are being generated today. The newly introduced functional similarity networks of the three organisms show different network properties as compared with the protein-protein interaction networks.
Functionality of the GAL4/UAS system in Tribolium requires the use of endogenous core promoters
Authors: Schinko Johannes B , Weber Markus , Viktorinova Ivana , Kiupakis Alexandros , Averof Michalis , Klingler Martin , Wimmer Ernst A , Bucher Gregor
Published: May 2010

Background

The red flour beetle Tribolium castaneum has developed into an insect model system second only to Drosophila. Moreover, as a coleopteran it represents the most species-rich metazoan taxon which also includes many pest species. The genetic toolbox for Tribolium research has expanded in the past years but spatio-temporally controlled misexpression of genes has not been possible so far.

Results

Here we report the establishment of the GAL4/UAS binary expression system in Tribolium castaneum. Both GAL4Δ and GAL4VP16 driven by the endogenous heat shock inducible promoter of the Tribolium hsp68 gene are efficient in activating reporter gene expression under the control of the Upstream Activating Sequence (UAS). UAS driven ubiquitous tGFP fluorescence was observed in embryos within four hours after activation while in-situ hybridization against tGFP revealed expression already after two hours. The response is quick in relation to the duration of embryonic development in Tribolium - 72 hours with segmentation being completed after 24 hours - which makes the study of early embryonic processes possible using this system. By comparing the efficiency of constructs based on Tribolium, Drosophila, and artificial core promoters, respectively, we find that the use of endogenous core promoters is essential for high-level expression of transgenic constructs.

Conclusions

With the established GAL4/UAS binary expression system, ectopic misexpression approaches are now feasible in Tribolium. Our results support the contention that high-level transgene expression usually requires endogenous regulatory sequences, including endogenous core promoters in Tribolium and probably also other model systems.
Convergent evolution of RFX transcription factors and ciliary genes predated the origin of metazoans
Authors: Chu Jeffrey SC , Baillie David L , Chen Nansheng
Published: May 2010

Background

Intraflagellar transport (IFT) genes, which are critical for the development and function of cilia and flagella in metazoans, are tightly regulated by the Regulatory Factor X (RFX) transcription factors (TFs). However, how and when their evolutionary relationship was established remains unknown.

Results

We have identified evidence suggesting that RFX TFs and IFT genes evolved independently and their evolution converged before the first appearance of metazoans. Both ciliary genes and RFX TFs exist in all metazoans as well as some unicellular eukaryotes. However, while RFX TFs and IFT genes are found simultaneously in all sequenced metazoan genomes, RFX TFs do not co-exist with IFT genes in most pre-metazoans and thus do not regulate them in these organisms. For example, neither the budding yeast nor the fission yeast possesses cilia although both have well-defined RFX TFs. Conversely, most unicellular eukaryotes, including the green algaChlamydomonas reinhardtii, have typical cilia and well conserved IFT genes but lack RFX TFs. Outside of metazoans, RFX TFs and IFT genes co-exist only in choanoflagellates includingM. brevicollis, and only one fungusAllomyces macrogynusof the 51 sequenced fungus genomes.M. brevicollishas two putative RFX genes and a full complement of ciliary genes.

Conclusions

The evolution of RFX TFs and IFT genes were independent in pre-metazoans. We propose that their convergence in evolution, or the acquired transcriptional regulation of IFT genes by RFX TFs, played a pivotal role in the establishment of metazoan.
FLU, an amino acid substitution model for influenza proteins
Authors: Dang Cuong Cao , Le Quang Si , Gascuel Olivier , Le Vinh Sy
Published: May 2010

Background

The amino acid substitution model is the core component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Although several general amino acid substitution models have been estimated from large and diverse protein databases, they remain inappropriate for analyzing specific species, e.g., viruses. Emerging epidemics of influenza viruses raise the need for comprehensive studies of these dangerous viruses. We propose an influenza-specific amino acid substitution model to enhance the understanding of the evolution of influenza viruses.

Results

A maximum likelihood approach was applied to estimate an amino acid substitution model (FLU) from ~113, 000 influenza protein sequences, consisting of ~20 million residues. FLU outperforms 14 widely used models in constructing maximum likelihood phylogenetic trees for the majority of influenza protein alignments. On average, FLU gains ~42 log likelihood points with an alignment of 300 sites. Moreover, topologies of trees constructed using FLU and other models are frequently different. FLU does indeed have an impact on likelihood improvement as well as tree topologies. It was implemented in PhyML and can be downloaded fromftp://ftp.sanger.ac.uk/pub/1000genomes/lsq/FLUor included in PhyML 3.0 server athttp://www.atgc-montpellier.fr/phyml/.

Conclusions

FLU should be useful for any influenza protein analysis system which requires an accurate description of amino acid substitutions.
Plasmodium infection alters Anopheles gambiae detoxification gene expression
Authors: Félix Rute C , Müller Pie , Ribeiro Vera , Ranson Hilary , Silveira Henrique
Published: May 2010

Background

Anopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection. While many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. The current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of Plasmodium berghei infection in midgut and fat body tissues.

Results

Using a custom-made DNA microarray, transcript levels of 254 loci primarily belonging to three major detoxification enzyme families (glutathione S-transferases, cytochrome P450 monooxygenases and esterases) were compared in infected and uninfected mosquitoes both during ookinete invasion and the release of sporozoites into the hemocoel. The greatest changes in gene expression were observed in the midgut in response to ookinete invasion. Interestingly, many detoxification genes including a large number of P450s were down-regulated at this stage. In the fat body, while less dramatic, gene expression alterations were also observed and occurred during the ookinete invasion and during the release of sporozoites into the hemocoel. While most gene expression changes were tissue-related, CYP6M2, a CYP previously associated with insecticide resistance, was over-expressed both in the midgut and fat body during ookinete invasion.

Conclusions

Most toxicity-related reactions occur in the midgut shortly after the ingestion of an infected blood meal. Strong up-regulation of CYP6M2 in the midgut and the fat body as well as its previous association with insecticide resistance shows its broad role in metabolic detoxification.
The dissemination of C10 cysteine protease genes in Bacteroides fragilis by mobile genetic elements
Authors: Thornton Roibeard F , Kagawa Todd F , O'Toole Paul W , Cooney Jakki C
Published: May 2010

Background

The C10 family of cysteine proteases includes enzymes that contribute to the virulence of bacterial pathogens, such as SpeB in Streptococcus pyogenes. The presence of homologues of cysteine protease genes in human commensal organisms has not been examined. Bacteroides fragilis is a member of the dominant Bacteroidetes phylum of the human intestinal microbiota, and is a significant opportunistic pathogen.

Results

Four homologues of the streptococcal virulence factor SpeB were identified in the B. fragilis genome. These four protease genes, two were directly contiguous to open reading frames predicted to encode staphostatin-like inhibitors, with which the protease genes were co-transcribed. Two of these protease genes are unique to B. fragilis 638R and are associated with two large genomic insertions. Gene annotation indicated that one of these insertions was a conjugative Tn-like element and the other was a prophage-like element, which was shown to be capable of excision. Homologues of the B. fragilis C10 protease genes were present in a panel of clinical isolates, and in DNA extracted from normal human faecal microbiota.

Conclusions

This study suggests a mechanism for the evolution and dissemination of an important class of protease in major members of the normal human microbiota.
Ultrastructure and molecular phylogenetic position of a novel euglenozoan with extrusive episymbiotic bacteria: Bihospites bacati n. gen. et sp. (Symbiontida)
Authors: Breglia Susana A , Yubuki Naoji , Hoppenrath Mona , Leander Brian S
Published: May 2010

Background

Poorly understood but highly diverse microbial communities exist within anoxic and oxygen-depleted marine sediments. These communities often harbour single-celled eukaryotes that form symbiotic associations with different prokaryotes. During low tides in South-western British Columbia, Canada, vast areas of marine sand become exposed, forming tidal pools. Oxygen-depleted sediments within these pools are distinctively black at only 2-3 cm depth; these layers contain a rich variety of microorganisms, many of which are undescribed. We discovered and characterized a novel (uncultivated) lineage of heterotrophic euglenozoan within these environments using light microscopy, scanning and transmission electron microscopy, serial sectioning and ultrastructural reconstruction, and molecular phylogenetic analyses of small subunit rDNA sequences.

Results

Bihospites bacati n. gen. et sp. is a biflagellated microbial eukaryote that lives within low-oxygen intertidal sands and dies within a few hours of exposure to atmospheric oxygen. The cells are enveloped by two different prokaryotic episymbionts: (1) rod-shaped bacteria and (2) longitudinal strings of spherical bacteria, capable of ejecting an internal, tightly wound thread. Ultrastructural data showed that B. bacati possesses all of the euglenozoan synapomorphies. Moreover, phylogenetic analyses of SSU rDNA sequences demonstrated that B. bacati groups strongly with the Symbiontida: a newly established subclade within the Euglenozoa that includes Calkinsia aureus and other unidentified organisms living in low-oxygen sediments. B. bacati also possessed novel features, such as a compact C-shaped rod apparatus encircling the nucleus, a cytostomal funnel and a distinctive cell surface organization reminiscent of the pellicle strips in phagotrophic euglenids.

Conclusions

We characterized the ultrastructure and molecular phylogenetic position of B. bacati n. gen. et sp. Molecular phylogenetic analyses demonstrated that this species belongs to the Euglenozoa and currently branches as the earliest diverging member of the Symbiontida. This is concordant with ultrastructural features of B. bacati that are intermediate between C. aureus and phagotrophic euglenids, indicating that the most recent ancestor of the Symbiontida descended from phagotrophic euglenids. Additionally, the extrusive episymbionts in B. bacati are strikingly similar to so-called "epixenosomes", prokaryotes previously described in a ciliate species and identified as members of the Verrucomicrobia. These parallel symbioses increase the comparative context for understanding the origin(s) of extrusive organelles in eukaryotes and underscores how little we know about the symbiotic communities of marine benthic environments.
The null hypothesis significance test in health sciences research (1995-2006): statistical analysis and interpretation
Authors: Silva-Ayçaguer Luis Carlos , Suárez-Gil Patricio , Fernández-Somoano Ana
Published: May 2010

Background

The null hypothesis significance test (NHST) is the most frequently used statistical method, although its inferential validity has been widely criticized since its introduction. In 1988, the International Committee of Medical Journal Editors (ICMJE) warned against sole reliance on NHST to substantiate study conclusions and suggested supplementary use of confidence intervals (CI). Our objective was to evaluate the extent and quality in the use of NHST and CI, both in English and Spanish language biomedical publications between 1995 and 2006, taking into account the International Committee of Medical Journal Editors recommendations, with particular focus on the accuracy of the interpretation of statistical significance and the validity of conclusions.

Methods

Original articles published in three English and three Spanish biomedical journals in three fields (General Medicine, Clinical Specialties and Epidemiology - Public Health) were considered for this study. Papers published in 1995-1996, 2000-2001, and 2005-2006 were selected through a systematic sampling method. After excluding the purely descriptive and theoretical articles, analytic studies were evaluated for their use of NHST with P-values and/or CI for interpretation of statistical "significance" and "relevance" in study conclusions.

Results

Among 1,043 original papers, 874 were selected for detailed review. The exclusive use of P-values was less frequent in English language publications as well as in Public Health journals; overall such use decreased from 41% in 1995-1996 to 21% in 2005-2006. While the use of CI increased over time, the "significance fallacy" (to equate statistical and substantive significance) appeared very often, mainly in journals devoted to clinical specialties (81%). In papers originally written in English and Spanish, 15% and 10%, respectively, mentioned statistical significance in their conclusions.

Conclusions

Overall, results of our review show some improvements in statistical management of statistical results, but further efforts by scholars and journal editors are clearly required to move the communication toward ICMJE advices, especially in the clinical setting, which seems to be imperative among publications in Spanish.
SCN5Aallelic expression imbalance in African-Americans heterozygous for the common variant p.Ser1103Tyr
Authors: Killen Stacy AS , Kunic Jennifer , Wang Lily , Lewis Adele , Levy Bruce P , Ackerman Michael J , George Alfred L
Published: May 2010

Background

Heterozygous and homozygous carriers of SCN5A-p.Ser1103Tyr, a common genetic variant with functional effects among African-Americans, have an increased risk of sudden death. We hypothesized that some heterozygous carriers may have unequal expression of wild-type and variant alleles and secondarily that predominance of the variant gene copy could further increase risk for sudden death in this population.

Methods

We quantified allele-specific expression of SCN5A-p.Ser1103Tyr by real-time reverse-transcription polymerase chain reaction (RT-PCR) in heart tissue from heterozygous African-American infants, who died from sudden infant death syndrome (SIDS) or from other causes, to test for allelic expression imbalance.

Results

We observed significant allelic expression imbalance in 13 of 26 (50%) African-American infant hearts heterozygous for SCN5A-p.Ser1103Tyr, and a significant (p < 0.0001) bimodal distribution of log2 allelic expression ratios. However, there were no significant differences in the mean log2 allelic expression ratios in hearts of infants dying from SIDS as compared to infants dying from other causes and no significant difference in the proportion of cases with greater expression of the variant allele.

Conclusions

Our data provide evidence that SCN5A allelic expression imbalance occurs in African-Americans heterozygous for p.Ser1103Tyr, but this phenomenon alone does not appear to be a marker for risk of SIDS.
How does the New Cooperative Medical Scheme influence health service utilization? A study in two provinces in rural China
Authors: Yu Baorong , Meng Qingyue , Collins Charles , Tolhurst Rachel , Tang Shenglan , Yan Fei , Bogg Lennart , Liu Xiaoyun
Published: May 2010

Background

Many countries are developing health financing mechanisms to pursue the goal of universal coverage. In China, a rural health insurance system entitled New Cooperative Medical Scheme (NCMS) is being developed since 2003. Although there is concern about whether the NCMS will influence the serious situation of inequity in health service utilization in rural China, there is only limited evidence available. This paper aims to assess the utilisation of outpatient and inpatient services among different income groups and provinces under NCMS in rural China.

Methods

Using multistage sampling processes, a cross-sectional household survey including 6,147 rural households and 22,636 individuals, was conducted in six counties in Shandong and Ningxia Provinces, China. Chi-square test, Poisson regression and log-linear regression were applied to analyze the association between NCMS and the utilization of outpatient and inpatient services and the length of stay for inpatients. Qualitative methods including individual interview and focus group discussion were applied to explain and complement the findings from the household survey.

Results

NCMS coverage was 95.9% in Shandong and 88.0% in Ningxia in 2006. NCMS membership had no significant association with outpatient service utilization regardless of income level and location.

Inpatient service utilization has increased for the high income group under NCMS, but for the middle and low income, the change was not significant. Compared with non-members, NCMS members from Ningxia used inpatient services more frequently, while members from Shandong had a longer stay in hospital.

High medical expenditure, low reimbursement rate and difference in NCMS policy design between regions were identified as the main reasons for the differences in health service utilization.

Conclusions

Outpatient service utilization has not significantly changed under NCMS. Although utilization of inpatient service in general has increased under NCMS, people with high income tend to benefit more than the low income group. While providing financial protection against catastrophic medical expenditure is the principal focus of NCMS, this study recommends that outpatient services should be incorporated in future NCMS policy development. NCMS policy should also be more equity oriented to achieve its policy goal.
Study protocol: national research partnership to improve primary health care performance and outcomes for Indigenous peoples
Authors: Bailie Ross , Si Damin , Shannon Cindy , Semmens James , Rowley Kevin , Scrimgeour David J , Nagel Tricia , Anderson Ian , Connors Christine , Weeramanthri Tarun , Thompson Sandra , McDermott Robyn , Burke Hugh , Moore Elizabeth , Leon Dallas , Weston Richard , Grogan Haylene , Stanley Andrew , Gardner Karen
Published: May 2010

Background

Strengthening primary health care is critical to reducing health inequity between Indigenous and non-Indigenous Australians. The Audit and Best practice for Chronic Disease Extension (ABCDE) project has facilitated the implementation of modern Continuous Quality Improvement (CQI) approaches in Indigenous community health care centres across Australia. The project demonstrated improvements in health centre systems, delivery of primary care services and in patient intermediate outcomes. It has also highlighted substantial variation in quality of care. Through a partnership between academic researchers, service providers and policy makers, we are now implementing a study which aims to 1) explore the factors associated with variation in clinical performance; 2) examine specific strategies that have been effective in improving primary care clinical performance; and 3) work with health service staff, management and policy makers to enhance the effective implementation of successful strategies.

Methods/Design

The study will be conducted in Indigenous community health centres from at least six States/Territories (Northern Territory, Western Australia, New South Wales, South Australia, Queensland and Victoria) over a five year period. A research hub will be established in each region to support collection and reporting of quantitative and qualitative clinical and health centre system performance data, to investigate factors affecting variation in quality of care and to facilitate effective translation of research evidence into policy and practice. The project is supported by a web-based information system, providing automated analysis and reporting of clinical care performance to health centre staff and management.

Discussion

By linking researchers directly to users of research (service providers, managers and policy makers), the partnership is well placed to generate new knowledge on effective strategies for improving the quality of primary health care and fostering effective and efficient exchange and use of data and information among service providers and policy makers to achieve evidence-based resource allocation, service planning, system development, and improvements of service delivery and Indigenous health outcomes.
NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations
Authors: Fu Yi-Ping , Edvardsen Hege , Kaushiva Alpana , Arhancet Juan P , Howe Tiffany M , Kohaar Indu , Porter-Gill Patricia , Shah Anushi , Landmark-Høyvik Hege , Fosså Sophie D , Ambs Stefan , Naume Bjørn , Børresen-Dale Anne-Lise , Kristensen Vessela N , Prokunina-Olsson Ludmila
Published: May 2010

Background

A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER)+ versus ER- cancer.

Results

We found association between SNP rs11249433 and expression of the NOTCH2 gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of NOTCH2 was found to be lowest in tumors with TP53 mutations and highest in TP53 wild-type/ER+ tumors (p = 0.0059). In the latter group, the NOTCH2 expression was particularly increased in carriers of the risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p = 0.0062). Similar association between NOTCH2 expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015), but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of NOTCH2, a truncated version of NOTCH2 consisting of only the extracellular domain.

Conclusion

This is the first study to show that the expression of NOTCH2 differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER+ luminal cells in the breast. Therefore, increased expression of NOTCH2 in carriers of rs11249433 may promote development of ER+ luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of NOTCH2 expression by rs11249433 and the role of NOTCH2 splicing forms in breast cancer development.
Anti-obesity effect of an isoflavone fatty acid ester on obese mice induced by high fat diet and its potential mechanism
Authors: Yao Yao , Li Xiao-Bo , Zhao Wei , Zeng Yan-Yan , Shen Hong , Xiang Hua , Xiao Hong
Published: May 2010

Background

The novel compound 1a is one of the isoflavone fatty acid esters. In order to investigate the anti-obesity effect of compound 1a and its potential mechanism of influence in adipocyte differentiation, Obese male C57BL/6J mice induced by high-fat diet (HFD) and rat preadipocytes (3T3-L1 cell) were used.

Methods

After 4-week HFD induction, the obese model was made successfully. After treatment with compound 1a, mice plasma biochemistry parameters were analyzed. In addition, mice hepatic tissue slice was observed. In in vitro research, 3T3-L1 cell differentiation by Oil-Red-O staining and adipocyte apoptosis was detected by flow cytometry.

Results

The in vivo results implied that compound 1a significantly decreased the body weight, white adipose tissue weight of obesity mice(p < 0.05), reduced leptin and TG in plasma(p < 0.05), elevated HDL-C in serum(p < 0.05). The in vitro results suggested that compound 1a could significantly suppress the adipocyte viability and lipid accumulation in the differentiation of preadipocyte, and induce apoptosis in both preadipocytes and mature adipocytes(p < 0.05).

Conclusion

Compound 1a regulates serum lipid profiles, decreases adipose tissue mass and body weight gain by inducing adipocyte apoptosis in high fat diet induced mice. Thus, it may be used to treat obese patients with hypercholesterolemia and hypertriglyceridemia.
Effective inhibition of HCMV UL49 gene expression and viral replication by oligonucleotide external guide sequences and RNase P
Authors: Zhang WenJun , Li HongJian , Li YueQin , Zeng ZhiFeng , Li ShiQian , Zhang Xin , Zou Yi , Zhou TianHong
Published: May 2010

Background

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that typically causes asymptomatic infections in healthy individuals but may lead to serious complications in newborns and immunodeficient individuals. The emergence of drug-resistant strains of HCMV has posed a need for the development of new drugs and treatment strategies. Antisense molecules are promising gene-targeting agents for specific regulation of gene expression. External guide sequences (EGSs) are oligonucleotides that consist of a sequence complementary to a target mRNA and recruit intracellular RNase P for specific degradation of the target RNA. The UL49-deletion BAC of HCMV was significantly defective in growth in human foreskin fibroblasts. Therefore, UL49 gene may serve as a potential target for novel drug development to combat HCMV infection. In this study, DNA-based EGS molecules were synthesized to target the UL49 mRNA of human cytomegalovirus (HCMV).

Results

By cleavage activity assessing in vitro, the EGS aimed to the cleavage site 324 nt downstream from the translational initiation codon of UL49 mRNA (i.e. EGS324) was confirmed be efficient to direct human RNase P to cleave the target mRNA sequence. When EGS324 was exogenously administered into HCMV-infected human foreskin fibroblasts (HFFs), a significant reduction of ~76% in the mRNA and ~80% in the protein expression of UL49 gene, comparing with the cells transfected with control EGSs. Furthermore, a reduction of about 330-fold in HCMV growth were observed in HCMV-infected HFFs treated with the EGS.

Conclusions

These results indicated that UL49 gene was essential for replication of HCMV. Moreover, our study provides evidence that exogenous administration of a DNA-based EGS can be used as a potential therapeutic approach for inhibiting gene expression and replication of a human virus.
Vascular injuries following road traffic collisions in a high-income developing country: a prospective cohort study
Authors: Jawas Ali , Hammad Fayez , Eid Hani O , Abu-Zidan Fikri M
Published: May 2010

Background

The mechanism and pattern of vascular injury vary between different populations. The commonest mechanism of vascular injury in civilian practice is road traffic collisions. We aimed to prospectively study the incidence, detailed mechanism and anatomical distribution of hospitalized vascular trauma patients following road traffic collisions in a high-income developing country.

Methods

Data were collected prospectively on road traffic collision injuries in the whole city of Al-Ain, United Arab Emirates, from April 2006 to October 2007 with full details of mechanism of injury and its relation to sustained injuries.

Results

Out of 1008 patients in the registry, 13 patients had vascular injury, a calculated incidence of 1.87 cases/100 000 inhabitants per year. There were eight car occupants, four pedestrians, and one motorcyclist. Upper limb vascular injuries were the most common anatomical site (n = 4) followed by thoracic aorta (n = 3). All thoracic aortic injuries were acceleration injuries (pedestrians hit by a moving vehicle). None of the eight car occupants was wearing a seatbelt and the majority sustained a front impact deceleration injuries. The median injury severity score, hospital stay, and ICU stay were significantly higher in the vascular injury group compared with nonvascular group (P < 0.0001). Three patients died (23%); two due to severe liver trauma and one due to rupture thoracic aorta.

Conclusions

The incidence of hospitalized vascular injury due to road traffic collisions in Al-Ain city is 1.87 cases/100 000 inhabitants. These injuries occurred mainly in the upper part of the body. Seatbelt compliance of car occupants having vascular injuries was very low. Compliance with safety measures needs more enforcement in our community.
A rapid method for the generation of uniform acellular bone explants: a technical note
Authors: Jähn Katharina , Braunstein Volker , Furlong Pamela I , Simpson Angharad E , Richards R Geoff , Stoddart Martin J
Published: May 2010

Background

Bone graft studies lack standardized controls. We aim to present a quick and reliable method for the intra-operative generation of acellular bone explants.

Methods

Therefore, ovine cancellous bone explants from the iliac crest were prepared and used to test several methods for the induction of cell death. Over night heat inactivation was used as positive treatment control, methods to be investigated included UV light, or X- ray exposure, incubation in a hypotonic solution (salt-free water) and a short cycle of repeated freezing and thawing.

Results

Viability of treated and 2 days cultured bone explants was investigated by lactate dehydrogenase assay. Non-treated cultured control explants maintained around 50% osteocyte viability, while osteocyte survival after the positive treatment control was abolished. The most dramatic loss in cell viability, together with a low standard deviation, was a repeated cycle of freezing and thawing.

Conclusions

To summarize, we present a freeze-thaw method for the creation of acellular bone explants, which is easy to perform, not time-consuming and provides consistent results.
Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro
Authors: Huang Chen , Yang Guang , Jiang Tao , Huang Kejian , Cao Jun , Qiu Zhengjun
Published: May 2010

Background

Signal transducer and activator of transcription 3 (Stat3) is a member of the Janus-activated kinase(Jak)/Stat signaling pathway. Abnormal activation of Stat3 plays a critical role in metastasis and invasion in varieties of human tumors including pancreatic cancer. This study aimed to investigate the mechanisms of activation and blocking of the Stat3 signaling pathway and its effects on invasion and metastasis of human pancreatic cancer cells.

Methods

The Jak inhibitor AG490 and interleukin-6 (IL-6) were added to the culture media of human pancreatic cancer cells SW1990 and Capan-2, respectively. Cell growth was measured by MTT assays. Western blotting and immunocytochemistry were performed to detect phosphorylated Stat3 (p-Stat3) protein, while VEGF and MMP-2 mRNA and protein expression were examined with fluorescence quantitative polymerase chain reaction and Western blotting, respectively. The invasion ability of SW1990 and Capan-2 cells was determined by cell invasion assay.

Results

Stat3 was activated by IL-6 in Capan-2 cells; protein expression of p-Stat3 was increased significantly in Capan-2 cells. IL-6 remarkably promoted the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression were increased significantly. Also, IL-6 increased the invasion ability of Capan-2 cells. AG490 inhibited Stat3 activation in SW1990 cells. Western blotting and immunocytochemistry analysis showed that p-Stat3 protein expression was decreased significantly with AG490 treatment in SW1990 cells. AG490 remarkably inhibited the growth of Capan-2 cells (P < 0.05), and VEGF and MMP-2 mRNA and protein expression was decreased significantly. And AG490 decreased the invasion ability of SW1990 cells.

Conclusions

Abnormal activation of Stat3 plays an important role in the invasion and metastasis of pancreatic cancer. Activation and blocking of the Stat3 signaling pathway can affect invasion ability and expression of the VEGF and MMP-2 genes in pancreatic cancer cells. The Stat3 signaling pathway may provide a novel therapeutic target for treatment of pancreatic cancer.
The association between leptin, interleukin-6, and hip radiographic osteoarthritis in older people: a cross-sectional study
Authors: Stannus Oliver P , Jones Graeme , Quinn Stephen J , Cicuttini Flavia M , Dore Dawn , Ding Changhai
Published: May 2010

Introduction

The associations between leptin, interleukin (IL)-6, and hip radiographic osteoarthritis (OA) have not been reported, and their roles in obesity-related hip OA are unclear. The aim of this study was to describe the associations between leptin, IL-6, and hip radiographic osteoarthritis (ROA) in older adults.

Methods

A cross-sectional sample of 193 randomly selected subjects (mean age, 63 years; range, 52 to 78 years; 48% female subjects) were studied. Hip ROA, including joint-space narrowing (JSN) and osteophytes, was determined by anteroposterior radiograph. Serum levels of leptin and interleukin (IL)-6 were measured with radioimmunoassay. Fat mass was measured with dual-energy x-ray absorptiometry (DXA). Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.

Results

In multivariable analysis, hip JSN was associated with serum levels of leptin in the whole sample (β = 0.046 per μg/L, P = 0.024 for superior; β = 0.068 per μg/L, P = 0.004 for axial compartment) and IL-6 only in females (β = 0.241 per pg/ml, P = 0.002 for superior; β = 0.239 per pg/ml, P = 0.001 for axial compartment). The positive associations between body-composition measures (BMI, WHR, percentage total fat mass, and percentage trunk fat mass) and hip JSN in women became nonsignificant after adjustment for leptin but not for IL-6. No significant associations were found between leptin, IL-6, and the presence or severity of osteophytes.

Conclusions

This study suggests that metabolic and inflammatory mechanisms may play a role in the etiology of hip OA and that the associations between body composition and hip JSN are mediated by leptin, particularly in women.