bluuebunny/crossref_metadata_2025 huggingface dataset:
Threat to Life and Risk-Taking Behaviors: A Review of Empirical Findings and Explanatory Models
Authors: Ben-Zur Hasida , Zeidner Moshe
Published: February 2009

This article reviews the literature focusing on the relationship between perceived threat to life and risk-taking behaviors. The review of empirical data, garnered from field studies and controlled experiments, suggests that personal threat to life results in elevated risk-taking behavior. To account for these findings, this review proposes a number of theoretical explanations. These frameworks are grounded in divergent conceptual models: coping with stress, emotion regulation, replenishing of lost resources through self-enhancement, modifications of key parameters of cognitive processing of risky outcomes, and neurocognitive mechanisms. The review concludes with a number of methodological considerations, as well as directions for future work in this promising area of research.
Anatomy of Culturally Sensitive Interventions Promoting Nutrition and Exercise in Hispanics: A Critical Examination of Existing Literature
Authors: Mier Nelda , Ory Marcia G. , Medina Alvaro A.
Published: February 2009

Compared with non-Hispanic Whites, Hispanics experience a disproportionate burden of chronic diseases. Understanding the factors influencing the success of health programs in Hispanics requires a clearer examination of the principles and components of tailored interventions. This research comprises a comprehensive literature review of randomized controlled trials testing nutrition and exercise interventions tailored for Hispanics and an examination of how these interventions were constructed. The review of 18 interventions meeting study criteria suggests that most tailored programs promoting nutrition and exercise in Hispanics are theory driven and are informed by formative research. Also, the findings indicate that salient culturally sensitive intervention components are (a) bilingual and bicultural facilitators and materials, (b) family-based activities, (c) literacy-appropriate materials, and (d) social support. A clear understanding of Hispanic cultural values is also required. Further empirical examination is warranted to determine the factors mediating or predicting the efficacy of culturally sensitive health programs for Hispanics.
Strengthening Quality Assurance in Health Education: Recent Milestones and Future Directions
Authors: Taub Alyson , Birch David A. , Auld M. Elaine , Lysoby Linda , Rasar King Laura
Published: February 2009

The health education profession has a lengthy history of efforts to assure the quality of health education professional preparation and practice. These initiatives to improve the value and accountability of health education are not only beneficial to current practitioners and faculty but also to consumers, students, employers, other professional colleagues, and numerous other stakeholders. This article describes the movement during the last decade to further strengthen quality assurance in health education, including current credentialing mechanisms for individuals and academic programs, the efforts of three national accreditation task forces, and the 2006 Third National Congress for Institutions Preparing Health Educators (Dallas II). Post—Dallas II activities related to program accreditation and approval and individual certification are presented as well as future directions for the health education workforce.
Youth Participation in a Community Campaign to Pass a Clean Indoor Air Ordinance
Authors: Bozlak Christine Taggart , Kelley Michele A.
Published: February 2009

Because of the harmful effects of secondhand smoke, communities are organizing to pass clean indoor air policies. With youth being considered one of the most vulnerable populations to this health hazard, it can be strategic to campaigns and beneficial to the youth’s development to involve them in efforts to control this toxin. However, youth participation in health campaigns is limited because of barriers inherent in these initiatives. This article presents lessons learned from a qualitative case study on the youth involvement in a successful local clean indoor air campaign. Through the analysis of semistructured interviews with the adult members of the campaign, group interviews and questionnaire completion by the youth members of the campaign, and additional insight made possible by participant observation, recommendations are provided to engage and sustain youth involvement in local public health initiatives.
Pharmacotherapy and Lifestyle Interventions for Tension-Type Headaches
Authors: Woods Tonja M. , Dunican Kaelen C. , Desilets Alicia R.
Published: February 2009

The objective of this review was to evaluate the efficacy of pharmacotherapy and lifestyle interventions for tension-type headaches. Literature was obtained through a MEDLINE (1966 to April 2008) search and a bibliographic review of published articles. Key terms searched included tension-type headaches, chronic tension-type headaches, pharmacotherapy, and lifestyle therapy. The search was further limited to the English language. Tension-type headaches are the most common and least studied primary headache disorder. These headaches are characterized by mild to moderate bilateral pain that is described as dull, aching, and bandlike. Episodic tension-type headaches may be treated with mild analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; although treatment should be individualized, data suggest that NSAIDs may be considered first line. Chronic and frequent episodic tension-type headaches often require prophylactic therapy. Although tricyclic antidepressants are considered the drugs of choice for chronic tension-type headaches, preliminary trials with venlafaxine, mirtazapine, tizanidine, and topiramate have shown promise. Lifestyle interventions such as physical therapy, behavioral therapy, and acupuncture are often employed, despite the lack of sound clinical evidence to support their use. Preliminary data support the combination of a tricyclic antidepressant and behavioral therapy for chronic tension-type headache.
Potentiating effects of RAD001 (Everolimus) on vincristine therapy in childhood acute lymphoblastic leukemia
Authors: Crazzolara Roman , Cisterne Adam , Thien Marilyn , Hewson John , Baraz Rana , Bradstock Kenneth F. , Bendall Linda J.
Published: February 2009

Despite advances in the treatment of acute lymphoblastic leukemia (ALL), the majority of children who relapse still die of ALL. Therefore, the development of more potent but less toxic drugs for the treatment of ALL is imperative. We investigated the effects of the mammalian target of rapamycin inhibitor, RAD001 (Everolimus), in a nonobese diabetic/severe combined immunodeficiency model of human childhood B-cell progenitor ALL. RAD001 treatment of established disease increased the median survival of mice from 21.3 days to 42.3 days (P < .02). RAD001 together with vincristine significantly increased survival compared with either treatment alone (P < .02). RAD001 induced a cell-cycle arrest in the G0/1 phase with associated dephosphorylation of the retinoblastoma protein, and reduced levels of cyclin-dependent kinases 4 and 6. Ultrastructure analysis demonstrated the presence of autophagy and limited apoptosis in cells of RAD001-treated animals. In contrast, cleaved poly(ADP-ribose) polymerase suggested apoptosis in cells from animals treated with vincristine or the combination of RAD001 and vincristine, but not in those receiving RAD001 alone. In conclusion, we have demonstrated activity of RAD001 in an in vivo leukemia model supporting further clinical development of target of rapamycin inhibitors for the treatment of patients with ALL.
Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis
Authors: Yamamoto Miki L. , Clark Tyson A. , Gee Sherry L. , Kang Jeong-Ah , Schweitzer Anthony C. , Wickrema Amittha , Conboy John G.
Published: February 2009

Differentiating erythroid cells execute a unique gene expression program that insures synthesis of the appropriate proteome at each stage of maturation. Standard expression microarrays provide important insight into erythroid gene expression but cannot detect qualitative changes in transcript structure, mediated by RNA processing, that alter structure and function of encoded proteins. We analyzed stage-specific changes in the late erythroid transcriptome via use of high-resolution microarrays that detect altered expression of individual exons. Ten differentiation-associated changes in erythroblast splicing patterns were identified, including the previously known activation of protein 4.1R exon 16 splicing. Six new alternative splicing switches involving enhanced inclusion of internal cassette exons were discovered, as well as 3 changes in use of alternative first exons. All of these erythroid stage-specific splicing events represent activated inclusion of authentic annotated exons, suggesting they represent an active regulatory process rather than a general loss of splicing fidelity. The observation that 3 of the regulated transcripts encode RNA binding proteins (SNRP70, HNRPLL, MBNL2) may indicate significant changes in the RNA processing machinery of late erythroblasts. Together, these results support the existence of a regulated alternative pre-mRNA splicing program that is critical for late erythroid differentiation.
Urokinase-mediated recruitment of myeloid-derived suppressor cells and their suppressive mechanisms are blocked by MUC1/sec
Authors: Ilkovitch Dan , Lopez Diana M.
Published: February 2009

The transmembrane isoform of mucin 1 (MUC1/TM) is a well-recognized tumor antigen, contributing to tumorigenesis and immune evasion. Although MUC1/TM has been correlated with malignancy, we have previously reported on antitumor properties and prevention of tumor development by a secreted splice variant of MUC1 (MUC1/sec). Because myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-induced immunosuppression, we investigated their recruitment by tumor cells expressing either MUC1/TM or MUC1/sec. DA-3 tumor cells expressing MUC1/sec recruit dramatically lower levels of MDSCs, relative to MUC1/TM-expressing DA-3 cells. Because MUC1/sec was previously shown to down-regulate tumor expression of urokinase plasminogen activator (uPA), a protease linked to tumor aggressiveness and metastasis, the potential role of uPA in MDSC recruitment was investigated. Tumor-derived uPA is capable of recruiting MDSCs, and correlates with tumor development. In addition to diminishing recruitment of MDSCs, the effect of MUC1/sec on MDSC-suppressive mechanisms was investigated. MUC1/sec, or its unique immunoenhancing peptide, is capable of blocking expression of arginase 1 and production of reactive oxygen species in MDSCs, implicated in the suppression of T cells. These findings demonstrate a new mechanism of MDSC recruitment, and provide evidence that MUC1/sec has antitumor properties affecting MDSCs.
Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders
Authors: Ishii Takefumi , Wang Jiapeng , Zhang Wei , Mascarenhas John , Hoffman Ronald , Dai Ying , Wisch Nathaniel , Xu Mingjiang
Published: February 2009

Pruritus is a common symptom in patients with Philadelphia chromosome–negative myeloproliferative disorders (MPDs). The pathophysiology of MPD-associated pruritus is unclear. We have demonstrated that MPD mast cells (MCs) are involved by the malignant process. In the present study, we explored the hypothesis that MCs play an important role in the development of pruritogenesis in MPDs. We found that MPD MCs released significantly greater amounts of pruritogenic factors, including histamine, leukotrienes, and interleukin-31 (IL-31) than normal MCs. Elevated levels of IL-31 were also observed in MPD CD3+ cell-conditioned media. MPD MCs exhibited increased migratory behavior in response to stem cell factor or interleukin-8, which was associated with increased filamentous-actin content. Furthermore, the presence of pruritus in MPDs was statistically correlated with a greater number of MCs being generated by CD34+ cells, a greater number of MC colonies being formed by CD34+ cells, decreased apoptosis and prostaglandin D2 release by cultured MCs, and higher plasma levels of IL-31. These data demonstrate that functional abnormalities of MPD MCs probably lead to pruritogenesis in patients with MPDs. These studies provide cellular and molecular targets for the development of antipruritus drugs for patients with MPDs.
Antineoplastic activity of lentiviral vectors expressing interferon-α in a preclinical model of primary effusion lymphoma
Authors: Calabrò Maria Luisa , Gasperini Paola , Di Gangi Iole Maria , Indraccolo Stefano , Barbierato Massimo , Amadori Alberto , Chieco-Bianchi Luigi
Published: February 2009

The peculiar site of development of primary effusion lymphoma (PEL) highlights a specific role of body cavities in the pathogenesis of this neoplasia. We used a xenograft murine model of PEL to characterize the contribution of the host microenvironment to PEL growth. The activity of a murine (ie, host-specific) interferon-α1 (IFN-α1)–expressing lentiviral vector (mIFN-α1-LV) was compared with that of a human (h) IFN-α2b-LV. LVs efficiently delivered the transgene to PEL cells and conferred long-term transgene expression in vitro and in vivo. Treatment of PEL-injected severe combined immunodeficiency mice with hIFN-α2b-LV significantly prolonged mice survival and reduced ascites development. Interestingly, mIFN-α1-LV showed an antineoplastic activity comparable with that observed with hIFN-α2b-LV. As mIFN-α1 retained species-restricted activity in vitro, it probably acted in vivo on the intracavitary murine milieu. mIFN-α1–treated murine mesothelial cells were found to express tumor necrosis factor–related apoptosis-inducing ligand and to significantly trigger apoptosis of cocultured PEL cells in a tumor necrosis factor–related apoptosis-inducing ligand-dependent manner. These data suggest that the interaction between lymphomatous and mesothelial cells lining the body cavities may play a key role in PEL growth control and also indicate that the specific targeting of microenvironment may impair PEL development.
Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab
Authors: Hilchey Shannon P. , Hyrien Ollivier , Mosmann Tim R. , Livingstone Alexandra M. , Friedberg Jonathan W. , Young Faith , Fisher Richard I. , Kelleher Raymond J. , Bankert Richard B. , Bernstein Steven H.
Published: February 2009

The incorporation of rituximab, a chimeric anti-CD20 monoclonal antibody, into the therapeutic armamentarium for patients with follicular lymphoma (FL) has significantly improved treatment outcome for such patients. Despite the almost universal application of this therapy, however, its exact mechanism of action has not been completely defined. One proposed mechanism is that of a “vaccinal” effect, whereby FL cell kill by rituximab results in the elicitation of an FL-specific T-cell response. The demonstration that rituximab can even elicit such a response in patients has, to our knowledge, never been shown. We analyzed the response against the immunoglobulin expressed by the FL before and after rituximab monotherapy in 5 FL patients and found an increase in FL idiotype–specific T cells after rituximab in 4 of 5 patients. Our data thus provide “proof of principle” for the ability of passive immunotherapy with rituximab to elicit an active FL-specific cellular response.
Robust methods for accurate diagnosis using pan-microbiological oligonucleotide microarrays
Authors: Liu Yang , Sam Lee , Li Jianrong , Lussier Yves A
Published: February 2009

Background

To address the limitations of traditional virus and pathogen detection methodologies in clinical diagnosis, scientists have developed high-throughput oligonucleotide microarrays to rapidly identify infectious agents. However, objectively identifying pathogens from the complex hybridization patterns of these massively multiplexed arrays remains challenging.

Methods

In this study, we conceived an automated method based on the hypergeometric distribution for identifying pathogens in multiplexed arrays and compared it to five other methods. We evaluated these metrics: 1) accurate prediction, whether the top ranked prediction(s) match the real virus(es); 2) four accuracy scores.

Results

Though accurate prediction and high specificity and sensitivity can be achieved with several methods, the method based on hypergeometric distribution provides a significant advantage in term of positive predicting value with two to sixty folds the positive predicting values of other methods.

Conclusion

The proposed multi-specie array analysis based on the hypergeometric distribution addresses shortcomings of previous methods by enhancing signals of positively hybridized probes.
Leveraging existing biological knowledge in the identification of candidate genes for facial dysmorphology
Authors: Tipney Hannah J , Leach Sonia M , Feng Weiguo , Spritz Richard , Williams Trevor , Hunter Lawrence
Published: February 2009

Background

In response to the frequently overwhelming output of high-throughput microarray experiments, we propose a methodology to facilitate interpretation of biological data in the context of existing knowledge. Through the probabilistic integration of explicit and implicit data sources a functional interaction network can be constructed. Each edge connecting two proteins is weighted by a confidence value capturing the strength and reliability of support for that interaction given the combined data sources. The resulting network is examined in conjunction with expression data to identify groups of genes with significant temporal or tissue specific patterns. In contrast to unstructured gene lists, these networks often represent coherent functional groupings.

Results

By linking from shared functional categorizations to primary biological resources we apply this method to craniofacial microarray data, generating biologically testable hypotheses and identifying candidate genes for craniofacial development.

Conclusion

The novel methodology presented here illustrates how the effective integration of pre-existing biological knowledge and high-throughput experimental data drives biological discovery and hypothesis generation.
Phenotype forecasting with SNPs data through gene-based Bayesian networks
Authors: Malovini Alberto , Nuzzo Angelo , Ferrazzi Fulvia , Puca Annibale A , Bellazzi Riccardo
Published: February 2009

Background

Bayesian networks are powerful instruments to learn genetic models from association studies data. They are able to derive the existing correlation between genetic markers and phenotypic traits and, at the same time, to find the relationships between the markers themselves. However, learning Bayesian networks is often non-trivial due to the high number of variables to be taken into account in the model with respect to the instances of the dataset. Therefore, it becomes very interesting to use an abstraction of the variable space that suitably reduces its dimensionality without losing information. In this paper we present a new strategy to achieve this goal by mapping the SNPs related to the same gene to one meta-variable. In order to assign states to the meta-variables we employ an approach based on classification trees.

Results

We applied our approach to data coming from a genome-wide scan on 288 individuals affected by arterial hypertension and 271 nonagenarians without history of hypertension. After pre-processing, we focused on a subset of 24 SNPs. We compared the performance of the proposed approach with the Bayesian network learned with SNPs as variables and with the network learned with haplotypes as meta-variables. The results were obtained by running a hold-out experiment five times. The mean accuracy of the new method was 64.28%, while the mean accuracy of the SNPs network was 58.99% and the mean accuracy of the haplotype network was 54.57%.

Conclusion

The new approach presented in this paper is able to derive a gene-based predictive model based on SNPs data. Such model is more parsimonious than the one based on single SNPs, while preserving the capability of highlighting predictive SNPs configurations. The prediction performance of this approach was consistently superior to the SNP-based and the haplotype-based one in all the test sets of the evaluation procedure. The method can be then considered as an alternative way to analyze the data coming from association studies.
PhenoGO: an integrated resource for the multiscale mining of clinical and biological data
Authors: Sam Lee T , Mendonça Eneida A , Li Jianrong , Blake Judith , Friedman Carol , Lussier Yves A
Published: February 2009

The evolving complexity of genome-scale experiments has increasingly centralized the role of a highly computable, accurate, and comprehensive resource spanning multiple biological scales and viewpoints. To provide a resource to meet this need, we have significantly extended the PhenoGO database with gene-disease specific annotations and included an additional ten species. This a computationally-derived resource is primarily intended to provide phenotypic context (cell type, tissue, organ, and disease) for mining existing associations between gene products and GO terms specified in the Gene Ontology Databases Automated natural language processing (BioMedLEE) and computational ontology (PhenOS) methods were used to derive these relationships from the literature, expanding the database with information from ten additional species to include over 600,000 phenotypic contexts spanning eleven species from five GO annotation databases. A comprehensive evaluation evaluating the mappings (n = 300) found precision (positive predictive value) at 85%, and recall (sensitivity) at 76%. Phenotypes are encoded in general purpose ontologies such as Cell Ontology, the Unified Medical Language System, and in specialized ontologies such as the Mouse Anatomy and the Mammalian Phenotype Ontology. A web portal has also been developed, allowing for advanced filtering and querying of the database as well as download of the entire dataset http://www.phenogo.org.
Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes
Authors: Wilder Steven P , Kaisaki Pamela J , Argoud Karène , Salhan Anita , Ragoussis Jiannis , Bihoreau Marie-Thérèse , Gauguier Dominique
Published: February 2009

Background

Microarray technologies are widely used to quantify the abundance of transcripts corresponding to thousands of genes. To maximise the robustness of transcriptome results, we have tested the performance and reproducibility of rat and mouse gene expression data obtained with Affymetrix, Illumina and Operon platforms.

Results

We present a thorough analysis of the degree of reproducibility provided by analysing the transcriptomic profile of the same animals of several experimental groups under different popular microarray technologies in different tissues. Concordant results from inter- and intra-platform comparisons were maximised by testing many popular computational methods for generating fold changes and significances and by only considering oligonucleotides giving high expression levels. The choice of Affymetrix signal extraction technique was shown to have the greatest effect on the concordance across platforms. In both species, when choosing optimal methods, the agreement between data generated on the Affymetrix and Illumina was excellent; this was verified using qRT-PCR on a selection of genes present on all platforms.

Conclusion

This study provides an extensive assessment of analytical methods best suited for processing data from different microarray technologies and can assist integration of technologically different gene expression datasets in biological systems.
Understanding Haemophilus parasuis infection in porcine spleen through a transcriptomics approach
Authors: Chen Hongbo , Li Changchun , Fang Mingdi , Zhu Mengjin , Li Xinyun , Zhou Rui , Li Kui , Zhao Shuhong
Published: February 2009

Background

Haemophilus parasuis(HPS) is an important swine pathogen that causes Glässer's disease, which is characterized by fibrinous polyserositis, meningitis and arthritis. The molecular mechanisms that underlie the pathogenesis of the disease remain poorly understood, particularly the resistance of porcine immune system to HPS invasion. In this study, we investigated the global changes in gene expression in the spleen following HPS infection using the Affymetrix Porcine Genechip™.

Results

A total of 931 differentially expressed (DE) transcripts were identified in the porcine spleen 7 days after HPS infection; of these, 92 unique genes showed differential expression patterns based on analysis using BLASTX and Gene Ontology. The DE genes involved in the immune response included genes for inflammasomes (RETN,S100A8,S100A9,S100A12), adhesion molecules (CLDN3,CSPG2,CD44,LGALS8), transcription factors (ZBTB16,SLC39A14,CEBPD,CEBPB), acute-phase proteins and complement (SAA1,LTF,HP,C3), differentiation genes for epithelial cells and keratinocytes (TGM1,MS4A8B,CSTA), and genes related to antigen processing and presentation (HLA-B,HLA-DRB1). Further immunostimulation analyses indicated that mRNA levels ofS100A8,S100A9, andS100A12in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS) and Poly(I:C) respectively. In addition, mapping of DE genes to porcine health traits QTL regions showed that 70 genes were distributed in 7 different known porcine QTL regions. Finally, 10 DE genes were validated by quantitative PCR.

Conclusion

Our findings demonstrate previously unrecognized changes in gene transcription that are associated with HPS infectionin vivo, and many potential cascades identified in the study clearly merit further investigation. Our data provide new clues to the nature of the immune response in mammals, and we have identified candidate genes that are related to resistance to HPS.
Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization
Authors: van Riet Elly , Everts Bart , Retra Kim , Phylipsen Marion , van Hellemond Jaap J , Tielens Aloysius GM , van der Kleij Desiree , Hartgers Franca C , Yazdanbakhsh Maria
Published: February 2009

Background

Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing capacities are still poorly defined. To address this issue, the molecular profile of human monocyte derived DCs was characterized after exposure to TLR4 ligand LPS in combination with the Th1 promoting bacterial extracts fromListeria monocytogenesandEscherichia colior the Th2 promoting helminth derived phospholipids fromSchistosoma mansoniandAscaris lumbricoides, all with TLR2 activating capacity.

Results

With regard to the signalling pathways activated upon exposure to LPS and the TLR2 activating compounds, we find that the ratio of activated Mitogen Activated Protein Kinases (MAPK)p-ERK/p-p38 is lower in DCs stimulated with the bacterial products compared to DCs stimulated with the helminth products, which correlates with the Th1 and Th2 polarizing capacity of these compounds. Furthermore, analysis of the mRNA expression levels of a set of 25 carefully selected genes potentially involved in modulation of T cell polarization revealed that the mRNA expression of notch ligand delta-4 and transcription factor c-fos are differentially regulated and show a strong correlation with Th1 and Th2 polarization, respectively.

Conclusion

This study shows that combined TLR2 and TLR4 activation in the context of different antigen sources can induce very distinct molecular profiles in DCs and suggests that the Th1/Th2 polarizing capacity of compounds can be predicted with the molecular signature they induce in DCs.
DNA restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolates from HIV-seropositive and HIV-seronegative patients in Kampala, Uganda
Authors: Asiimwe Benon B , Joloba Moses L , Ghebremichael Solomon , Koivula Tuija , Kateete David P , Katabazi Fred A , Pennhag Alexander , Petersson Ramona , Kallenius Gunilla
Published: February 2009

Background

The identification and differentiation of strains of Mycobacterium tuberculosis by DNA fingerprinting has provided a better understanding of the epidemiology and tracing the transmission of tuberculosis. We set out to determine if there was a relationship between the risk of belonging to a group of tuberculosis patients with identical mycobacterial DNA fingerprint patterns and the HIV sero-status of the individuals in a high TB incidence peri-urban setting of Kampala, Uganda.

Methods

One hundred eighty three isolates of Mycobacterium tuberculosis from 80 HIV seropositive and 103 HIV seronegative patients were fingerprinted by standard IS6110-RFLP. Using the BioNumerics software, strains were considered to be clustered if at least one other patient had an isolate with identical RFLP pattern.

Results

One hundred and eighteen different fingerprint patterns were obtained from the 183 isolates. There were 34 clusters containing 54% (99/183) of the patients (average cluster size of 2.9), and a majority (96.2%) of the strains possessed a high copy number (≥ 5 copies) of the IS6110 element. When strains with <5 bands were excluded from the analysis, 50.3% (92/183) were clustered, and there was no difference in the level of diversity of DNA fingerprints observed in the two sero-groups (adjusted odds ratio [aOR] 0.85, 95%CI 0.46–1.56, P = 0.615), patients aged <40 years (aOR 0.53, 95%CI 0.25–1.12, P = 0.100), and sex (aOR 1.12, 95%CI 0.60–2.06, P = 0.715).

Conclusion

The sample showed evidence of a high prevalence of recent transmission with a high average cluster size, but infection with an isolate with a fingerprint found to be part of a cluster was not associated with any demographic or clinical characteristics, including HIV status.
Incidence of bacterial meningitis (2001–2005) in Lazio, Italy: the results of a integrated surveillance system
Authors: Giorgi Rossi Paolo , Mantovani Jessica , Ferroni Eliana , Forcina Antonio , Stanghellini Elena , Curtale Filippo , Borgia Piero
Published: February 2009

Background

Monitoring the incidence of bacterial meningitis is important to plan and evaluate preventive polices. The study's aim was to estimate the incidence of bacterial meningitis by aetiological agent in the period 2001–2005, in Lazio Italy (5.3 mln inhabitants).

Methods

Data collected from four sources – hospital surveillance of bacterial meningitis, laboratory information system, the mandatory infectious diseases notifications, and hospital information system – were combined into a single archive.

Results

944 cases were reported, 89% were classified as community acquired. S. pneumoniae was the most frequent aetiological agent in Lazio, followed by N. meningitis. Incidence of H. influenzae decreased during the period. 17% of the cases had an unknown aetiology and 13% unspecified bacteria. The overall incidence was 3.7/100,000. Children under 1 year were most affected (50.3/100.000), followed by 1–4 year olds (12.5/100,000). The percentage of meningitis due to aetiological agents included in the vaccine targets, not considering age, is 31%. Streptococcus spp. was the primary cause of meningitis in the first three months of life. The capture-recapture model estimated underreporting at 17.2% of the overall incidence.

Conclusion

Vaccine policies should be planned and monitored based on these results. The integrated surveillance system allowed us to observe a drop in H. influenzae b meningitis incidence consequent to the implementation of a mass vaccination of newborns.
How do medical students value health on the EQ-5D? Evaluation of hypothetical health states compared to the general population
Authors: Barbist Maria-Theresa , Renn Daniela , Noisternig Bianca , Rumpold Gerhard , Höfer Stefan
Published: February 2009

Background

Medical students gain a particular perspective on health problems during their medical education. This article describes how medical students value 10 hypothetical health states using the EQ-5D compared to the general population.

Methods

Based on a sample of 161 medical students (male: 41%) we compared valuations of 10 hypothetical EQ-5D health states collected in face to face interviews with the valuations of the general population. Self-reported health on the EQ-5D was also collected.

Results

Every third health state was valuated higher by the medical students compared to data of the general population. The differences were independent of the severity of the hypothetical health state. Concerning the self-reported health, the majority of the students (66%) reported no problems in the five EQ-5D domains (EQ-5D VAS M = 87.3 ± 9.6 SD). However, when compared to an age-matched sample the medical students show significantly more problems in the area of pain/discomfort and anxiety/depression.

Conclusion

Medical students have a tendency to value health states higher than the general public. Medical professionals should be continuously aware that their assessment of the patients health state can differ from the valuations of the general population.
Drugs targeting the mitochondrial pore act as citotoxic and cytostatic agents in temozolomide-resistant glioma cells
Authors: Lena Annalisa , Rechichi Mariarosa , Salvetti Alessandra , Bartoli Barbara , Vecchio Donatella , Scarcelli Vittoria , Amoroso Rosina , Benvenuti Lucia , Gagliardi Rolando , Gremigni Vittorio , Rossi Leonardo
Published: February 2009

Background

High grade gliomas are one of the most difficult cancers to treat and despite surgery, radiotherapy and temozolomide-based chemotherapy, the prognosis of glioma patients is poor. Resistance to temozolomide is the major barrier to effective therapy. Alternative therapeutic approaches have been shown to be ineffective for the treatment of genetically unselected glioma patients. Thus, novel therapies are needed. Mitochondria-directed chemotherapy is an emerging tool to combat cancer, and inner mitochondrial permeability transition (MPT) represents a target for the development of cytotoxic drugs. A number of agents are able to induce MPT and some of them target MPT-pore (MPTP) components that are selectively up-regulated in cancer, making these agents putative cancer cell-specific drugs.

Objective

The aim of this paper is to report a comprehensive analysis of the effects produced by selected MPT-inducing drugs (Betulinic Acid, Lonidamine, CD437) in a temozolomide-resistant glioblastoma cell line (ADF cells).

Methods

EGFRvIII expression has been assayed by RT-PCR. EGFR amplification and PTEN deletion have been assayed by differential-PCR. Drugs effect on cell viability has been tested by crystal violet assay. MPT has been tested by JC1 staining. Drug cytostatic effect has been tested by mitotic index analysis. Drug cytotoxic effect has been tested by calcein AM staining. Apoptosis has been assayed by Hoechst incorporation and Annexine V binding assay. Authophagy has been tested by acridine orange staining.

Results

We performed a molecular and genetic characterization of ADF cells and demonstrated that this line does not express the EGFRvIII and does not show EGFR amplification. ADF cells do not show PTEN mutation but differential PCR data indicate a hemizygous deletion of PTEN gene. We analyzed the response of ADF cells to Betulinic Acid, Lonidamine, and CD437. Our data demonstrate that MPT-inducing agents produce concentration-dependent cytostatic and cytotoxic effects in parallel with MPT induction triggered through MPTP. CD437, Lonidamine and Betulinic acid trigger apoptosis as principal death modality.

Conclusion

The obtained data suggest that these pharmacological agents could be selected as adjuvant drugs for the treatment of high grade astrocytomas that resist conventional therapies or that do not show any peculiar genetic alteration that can be targeted by specific drugs.
A large new subset of TRIM genes highly diversified by duplication and positive selection in teleost fish
Authors: van der Aa Lieke M , Levraud Jean-Pierre , Yahmi Malika , Lauret Emilie , Briolat Valérie , Herbomel Philippe , Benmansour Abdenour , Boudinot Pierre
Published: February 2009

Background

In mammals, the members of the tripartite motif (TRIM) protein family are involved in various cellular processes including innate immunity against viral infection. Viruses exert strong selective pressures on the defense system. Accordingly, antiviral TRIMs have diversified highly through gene expansion, positive selection and alternative splicing. Characterizing immune TRIMs in other vertebrates may enlighten their complex evolution.

Results

We describe here a large new subfamily of TRIMs in teleosts, called finTRIMs, identified in rainbow trout as virus-induced transcripts. FinTRIMs are formed of nearly identical RING/B-box regions and C-termini of variable length; the long variants include a B30.2 domain. The zebrafish genome harbors a striking diversity of finTRIMs, with 84 genes distributed in clusters on different chromosomes. A phylogenetic analysis revealed different subsets suggesting lineage-specific diversification events. Accordingly, the number offintrimgenes varies greatly among fish species. Conserved syntenies were observed only for the oldestfintrims. The closest mammalian relatives aretrim16andtrim25, but they are not true orthologs. The B30.2 domain of zebrafish finTRIMs evolved under strong positive selection. The positions under positive selection are remarkably congruent in finTRIMs and in mammalian antiviral TRIM5α, concentrated within a viral recognition motif in mammals. The B30.2 domains most closely related to finTRIM are found among NOD-like receptors (NLR), indicating that the evolution of TRIMs and NLRs was intertwined by exon shuffling.

Conclusion

The diversity, evolution, and features of finTRIMs suggest an important role in fish innate immunity; this would make them the first TRIMs involved in immunity identified outside mammals.
Susceptibility of rheumatoid arthritis synovial fibroblasts to FasL- and TRAIL-induced apoptosis is cell cycle-dependent
Authors: Pundt Noreen , Peters Marvin A , Wunrau Christina , Strietholt Simon , Fehrmann Carsten , Neugebauer Katja , Seyfert Christine , van Valen Frans , Pap Thomas , Meinecke Ingmar
Published: February 2009

Introduction

The rheumatoid arthritis (RA) synovium is characterised by the presence of an aggressive population of activated synovial fibroblasts (RASFs) that are prominently involved in the destruction of articular cartilage and bone. Accumulating evidence suggests that RASFs are relatively resistant to Fas-ligand (FasL)-induced apoptosis, but the data concerning tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) have been conflicting. Here, we hypothesise that the susceptibility of RASFs to receptor-mediated apoptosis depends on the proliferation status of these cells and therefore analysed the cell cycle dependency of FasL- and TRAIL-induced programmed cell death of RASFs in vitro.

Methods

Synovial fibroblasts were isolated from patients with RA by enzymatic digestion and cultured under standard conditions. Cell cycle analysis was performed using flow cytometry and staining with propidium iodide. RASFs were synchronised or arrested in various phases of the cell cycle with 0.5 mM hydroxyurea or 2.5 μg/ml nocodazol and with foetal calf serum-free insulin-transferrin-sodium selenite supplemented medium. Apoptosis was induced by stimulation with 100 ng/ml FasL or 100 ng/ml TRAIL over 18 hours. The apoptotic response was measured using the Apo-ONE® Homogenous Caspase-3/7 Assay (Promega GmbH, Mannheim, Germany) and the Cell Death Detection (ELISAPlus) (enzyme-linked immunosorbent assay) (Roche Diagnostics GmbH, Mannheim, Germany). Staurosporin-treated cells (1 μg/ml) served as a positive control. Expression of Fas and TRAIL receptors (TRAILR1-4) was determined by fluorescence-activated cell sorting analysis.

Results

Freshly isolated RASFs showed only low proliferation in vitro, and the rate decreased further over time, particularly when RASFs became confluent. RASFs expressed Fas, TRAIL receptor-1, and TRAIL receptor-2, and the expression levels were independent of the cell cycle. However, the proliferation rate significantly influenced the susceptibility to FasL- and TRAIL-induced apoptosis. Specifically, proliferating RASFs were less sensitive to FasL- and TRAIL-induced apoptosis than RASFs with a decreased proliferation rate. Furthermore, RASFs that were synchronised in S phase or G2/M phase were less sensitive to TRAIL-induced apoptosis than synchronised RASFs in G0/G1 phase.

Conclusions

Our data indicate that the susceptibility of RASFs to FasL- and TRAIL-induced apoptosis depends on the cell cycle. These results may explain some conflicting data on the ability of RASFs to undergo FasL- and TRAIL-mediated cell death and suggest that strategies to sensitise RASFs to apoptosis may include the targeting of cell cycle-regulating genes.
Numerical analysis of laminar natural convection in isosceles triangular enclosures
Authors: Kent E F
Published: February 2009

In this work, a numerical analysis of laminar natural convection in an isosceles triangular enclosure has been performed for two different thermal boundary conditions. In case 1, the base is heated and the two inclined walls are symmetrically cooled, and in case 2, the base is cooled and the two top inclined walls are symmetrically heated. This configuration is encountered in solar engineering applications such as: solar stills that usually have triangular cavities and triangular built-in-storage-type solar water heaters; and heat transfer in attic spaces in both wintertime and summertime conditions. To perform the computational analysis, the finite-volume method is used for the discretization of the governing equations. Base angles varying from 15 to 75° have been used for different Rayleigh numbers ranging from 103 to 105. The effects of the Rayleigh number and aspect ratio on the flow field and heat transfer are analysed. The detailed streamline patterns and temperature distributions are presented. The variation of the mean Nusselt numbers versus Rayleigh numbers for different base angles is given. It is found that the base angle has a drastic influence on the flow field and isotherms for the two cases. For case 1, at small base angles, as the Rayleigh number increases, a multi-cellular flow structure developed inside the enclosure enhances the heat transfer. For case 2, the temperature profiles are always stable and stratified for all Rayleigh numbers and base angles.
Forward displacement analysis of a new 1CCC–5SPS parallel mechanism using Gröbner theory
Authors: Gan D , Liao Q , Dai J S , Wei S , Seneviratne L D
Published: February 2009

A new parallel mechanism 1CCC–5SPS which has distance and angle constraints is introduced in this article. Degree of freedom and forward kinematic analysis of this new parallel mechanism are presented, in which four equivalent polynomial equations are obtained from the original six geometrical constraint equations. The Gröbner basis theory is used with the four equations and the problem of forward displacement is reduced to a 40th degree polynomial equation in a single unknown from a constructed 10 × 10 Sylvester's matrix which is small in size, from which 40 different locations of the moving platform can be derived. A numerical example confirms the efficiency of the procedure.
Vibrational and acoustic radiation from a submerged periodic cylindrical shell with axial stiffening
Authors: Liao C-J , Jiang W-K , Duan H , Wang Y
Published: February 2009

An analytical study on the vibration and acoustic radiation from an axially stiffened cylindrical shell in water is presented. Supposing that the axial stiffeners interact with the cylindrical shell only through radial forces, the reaction forces on the shell from stiffeners can be expressed by additional impedance. The coupled vibration equation of the finite cylindrical shell with axial stiffening is derived; in this equation additional impedance caused by the axial stiffeners is added. As a result, the vibration and sound radiation of the shell are dependent on the mechanical impedance of the shell, the radiation sound impedance, and the additional impedance of the axial stiffeners. Based on the numerical simulation, it is found that the existence of axial stiffeners decreases the sound radiation and surface average velocity, whereas it increases the radiation factor. The characteristics of the acoustic radiation can be understood from the simulation with good results, which show that the presented methodology can be used to study the mechanism of the acoustic radiation of the complicated cylindrical shell and to optimize its design.
Experimental and numerical studies of synthetic jets driven by a dual-diaphragm piezoelectric actuator
Authors: Yang A-S , Ro J-J , Chang W-H
Published: February 2009

The applications of piezoelectric synthetic jet actuators have shown great potential as active flow control devices. The objective of this study is to investigate the flow phenomenon of a synthetic jet generated by a dual-diaphragm piezo-driven actuator. In this analysis, the computational approach adopted unsteady three-dimensional conservation equations of mass and momentum for examining the development process of synthetic jets. The moving boundary was also treated to represent the motion of the piezo diaphragm. Experimentally, a flow visualization system was employed to acquire the particle-streak images scattered from red fluorescent spheres for observing the synthetic jet flow. The jet velocity along the centre-line was also measured by using a hot-wire anemometer. The system test results demonstrated a satisfactory functioning of the actuator for producing synthetic jets. The predictions were then compared with the visualized particle-streak images and the measured centre-line velocity of the synthetic jet to validate the computer software. In the near-field, both simulation results and experimental observations revealed the time-cyclical formation and advection of a vortex pair in a full sinusoidal actuation cycle at an operating frequency of 4 Hz. When the vortex pair travelled well downstream, the ambient air from the vicinity of the slot was entrained into the cavity of the actuator. However, the overall far-field flow pattern, characterized by longitudinal decay of the centre-line velocity and lateral spreading, resembled a conventional continuous air-jet in essence.
Geometrical conditions for wedging in mechanical systems with Coulomb friction
Authors: Zhechev M M , Khramova M V
Published: February 2009

It is known that a phenomenon referred to as wedging can occur in mechanical systems with friction. This phenomenon occurs in certain system positions, and an actual mechanical system can be started from a wedged position only at the cost of irreversible deformations. Although the results of the theoretical study of wedging are of great importance in the development and operation of process automation systems, the theory of this phenomenon is still in the making.

In this work, the notion of a wedgeable system is introduced and its rigorous definition is given. Within the framework of the traditional formulation, this definition reflects the properties of wedging in actual mechanical systems in the most adequate manner. Based on this notion, a number of statements on wedging conditions in mechanical systems with two and three frictional contacts are proved. Simple, convenient in use rules are given for identifying the possibility of wedging in peg-in-hole systems with two and three frictional contacts.