bluuebunny/crossref_metadata_2025 huggingface dataset:
World Overview
Authors: Holland Dawn , Delannoy Aurélie , Fic Tatiana , Hurst Ian , Liadze Iana , Orazgani Ali , Paluchowski Paweł
Published: November 2011

Global economic prospects have deteriorated markedly in recent months. Risks around our central forecast have shifted distinctly to the downside. Much of this is due to the heightened uncertainty surrounding Europe's sovereign debt crisis. There is widespread agreement among policymakers - ranging from the IMF, European Commission and European Central Bank to individual heads of state both within and outside the Euro Area - that resolution to the crisis requires urgent, comprehensive and coordinated action. Yet 17 months after the first bail-out programme was introduced in Greece, policymakers have failed to deliver a strategy that promises a credible prospect of growth and an end to rising debt profiles. Solvency concerns in three relatively small peripheral countries (Greece, Ireland and Portugal), combined with weakening growth across the continent, raise the dangerous spectre of illiquidity beginning to affect solvency in the larger core economies with high debt ratios - notably Italy. Left unchecked, the consequences would be severe for the world economy.
Isolation of pectin-enriched products from red beet (Beta vulgaris L. var. conditiva) wastes: composition and functional properties
Authors: Fissore E.N. , Ponce N.M.A. , Matkovic L. , Stortz C.A. , Rojas A.M. , Gerschenson L.N.
Published: November 2011

The present work was dedicated to the development of an extraction process for red beet ( Beta vulgaris L. var. conditiva) by-products that preserves the high molecular weight of the macromolecules with the primary aim of waste upgrading. Our study concerns the extraction of pectin-enriched products with potential thickening properties for their usage in food formulation, as well as with some healthy physiological effect, by using citrate buffer (pH = 5.2) either alone or with enzymes (hemicellulase or cellulase) active on cell wall polysaccharide networks. Considering that red beet tissue contains ferulic acid, which cross-links pectin macromolecules through arabinose residues to anchor them into the cell wall, an alkaline pretreatment was also evaluated in order to perform polysaccharide hydrolysis in the cell wall network to accomplish higher renderings. Chemical composition and yield, as well as the in vitro glucose retention exerted by the isolated fiber products were finally analyzed.
Questioning the Specificity of ASRS-v1.1 to Accurately Detect ADHD in Substance Abusing Populations
Authors: Chiasson Jean-Pierre , Stavro Katherine , Rizkallah Élie , Lapierre Luc , Dussault Maxime , Legault Louis , Potvin Stéphane
Published: November 2011

Objective: To assess the specificity of the Adult ADHD Self-Report Scale (ASRS-v1.1) in detecting ADHD among individuals with substance use disorders (SUDs). Method: A chart review of 183 SUD patients was conducted. Patients were screened for ADHD with the ASRS-v1.1 and were later assessed by a psychiatrist specialized in ADHD. Results: Among SUD patients scoring positive results on the ASRS-v1.1 for the presence of ADHD, the ADHD diagnosis could only be confirmed in 26% of the sample by an expert psychiatrist. Conclusion: The ASRS-v1.1 reports low specificity in detecting ADHD among SUD populations.
Cognitive hermeneutics: The better alternative
Authors: Tepe Peter
Published: November 2011

This article critically assesses Bell’s attempt at transforming discourse analysis into discourse interpretation by means of hermeneutics as developed by Paul Ricoeur. If a hermeneutic turn is to take place in a discipline that proceeds according to the principles of empirical research, cognitive hermeneutics is the better option compared to Ricoeur’s hermeneutics. Part I presents a short introduction to cognitive hermeneutics as developed by Tepe. Against this background, some central theses of Ricoeur’s hermeneutics, on which Bell’s approach is based, are discussed in part II.
Religious Soft Power as Accountability Mechanism for Power in World Politics
Authors: Steiner Sherrie
Published: November 2011

This case study of the InterFaith Leaders’ Summit(s) from 2005 to 2010 expands the concept of “soft power” as an accountability mechanism to include religious soft power. This article explores the theoretical validity of a Faith-Based Accountability Mechanism (FAM) as a macro-level explanatory unit. The interfaith leaders exercise public reputational and peer accountability among their constituents in relation to the G8/G20 leaders. The theoretical validity of the dialogue process is not contingent on political leader responsiveness but is ascertained using a complex theoretical standard for assessing the legitimacy of global governance institutions against which observations are then gauged. The InterFaith Dialogue Mechanism is a specific illustration of a FAM that shows increasing compliance with the complex standard between 2005 and 2010. The Dialogue Mechanism FAM is a form of religious soft power that combines soft institution with soft technique. The next stage in the research is to identify specific characteristics of the FAM ideal type.
Antigen stored in dendritic cells after macropinocytosis is released unprocessed from late endosomes to target B cells
Authors: Le Roux Delphine , Le Bon Agnès , Dumas Audrey , Taleb Kahina , Sachse Martin , Sikora Romain , Julithe Marion , Benmerah Alexandre , Bismuth Georges , Niedergang Florence
Published: November 2011

B lymphocytes can be triggered in lymph nodes by nonopsonized antigens (Ag), potentially in their native form. However, the mechanisms that promote encounter of B lymphocytes with unprocessed antigens in lymph nodes are still elusive. We show here that antigens are detected in B cells in the draining lymph nodes of mice injected with live, but not fixed, dendritic cells (DCs) loaded with antigens. This highlights active processes in DCs to promote Ag transfer to B lymphocytes. In addition, antigen-loaded DCs found in the draining lymph node were CD103+. Using 3 different model Ag, we then show that immature DCs efficiently take up Ag by macropinocytosis and store the internalized material in late endocytic compartments. We find that DCs have a unique ability to release antigens from these compartments in the extracellular medium, which is controlled by Rab27. B cells take up the regurgitated Ag and the chemokine CXCL13, essential to attract B cells in lymph nodes, enhances this transfer. Our results reveal a unique property of DCs to regurgitate unprocessed Ag that could play an important role in B-cell activation.
Cyclic AMP response element-binding protein prevents endothelial permeability increase through transcriptional controlling p190RhoGAP expression
Authors: Chava Koteswara Rao , Tauseef Mohammad , Sharma Tiffany , Mehta Dolly
Published: November 2011

Increased endothelial permeability contributes to the morbidity and mortality associated with chronic inflammatory diseases, including acute lung injury. Cyclic AMP response element-binding protein (CREB) transcriptional factor induces genes that regulate inflammation and vascular remodeling. However, the role of CREB in regulating endothelial barrier function is unknown. Here, we demonstrate that CREB maintains basal endothelial barrier function and suppresses endothelial permeability increase by diverse agonists such as thrombin, lipopolysaccharide, histamine, and VEGF. We show that CREB transcriptionally controls the expression of p190RhoGAP-A, a GTPase-activating protein that inhibits small GTPase RhoA. Impairing CREB function using small interfering RNA or dominant-negative (dn)–CREB mutant (dn-CREB) markedly suppressed p190RhoGAP-A expression, increased RhoA activity, induced actin stress fiber formation, and produced an amplified and protracted increase in endothelial permeability in response to thrombin. Rescuing p190RhoGAP-A expression restored the permeability defect in dn-CREB–transducing endothelial cells. These findings were recapitulated in vivo because dn-CREB expression in mice vasculature increased basal lung microvessel permeability and exaggerated permeability increase induced by thrombin and lipopolysaccharide. Inhibiting RhoA signaling restored endothelial barrier dysfunction in the dn-CREB–expressing lung microvasculature. These results uncover a pivotal role of CREB in regulating endothelial barrier function by restricting RhoA signaling through controlling p190RhoGAP-A expression.
Increased serum soluble IL-15Rα levels in T-cell large granular lymphocyte leukemia
Authors: Chen Jing , Petrus Mike , Bamford Richard , Shih Joanna H. , Morris John C. , Janik John E. , Waldmann Thomas A.
Published: November 2011

Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disease of mature T and natural killer cells. The etiology of LGL leukemia is unknown. IL-15 is an inflammatory cytokine that stimulates T and natural killer cells and is critical for their survival and proliferation. IL-15 signals through a heterotrimeric receptor that is composed of a private receptor, IL-15Rα and IL-2/IL-15Rβ and γc shared with IL-2. Using a newly developed assay, we demonstrated increased levels of soluble IL-15Rα in the serum of patients with T-LGL leukemia. Furthermore, IL-15Rα mRNA levels were also up-regulated in the PBMCs of these patients. FACS analysis indicated that IL-15Rα was expressed both on monocytes as well as on some CD8+ leukemic cells of the patients. Interestingly, the mRNA levels of IFN-γ, a known inducer of IL-15Rα, were also up-regulated in patients' PBMCs. Moreover, PBMCs of some T-LGL patients proliferated at higher levels in response to exogenously added IL-15 compared with those of normal donors. In summary, our study demonstrated increased expression of IL-15Rα in T-LGL leukemia. It is conceivable that higher IL-15Rα expression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease.
Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols
Authors: Breccia Massimo , Mazzarella Luca , Bagnardi Vincenzo , Disalvatore Davide , Loglisci Giuseppina , Cimino Giuseppe , Testi Anna Maria , Avvisati Giuseppe , Petti Maria Concetta , Minotti Clara , Latagliata Roberto , Foà Robin , Pelicci Pier Giuseppe , Lo-Coco Francesco
Published: November 2011

We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI ≥ 25). An increased BMI was associated with older age (P < .0001) and male sex (P = .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio = 7.24; 95% CI, 1.50-34; P = .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P = .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio = 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P = .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols.
Aldose reductase deficiency in mice protects from ragweed pollen extract (RWE)-induced allergic asthma
Authors: Yadav Umesh CS , Aguilera-Aguirre Leopoldo , Boldogh Istvan , Ramana Kota V , Srivastava Satish K
Published: November 2011

Background

Childhood hospitalization related to asthma remains at historically high levels, and its incidence is on the rise world-wide. Previously, we have demonstrated that aldose reductase (AR), a regulatory enzyme of polyol pathway, is a major mediator of allergen-induced asthma pathogenesis in mouse models. Here, using AR null (AR-/-) mice we have investigated the effect of AR deficiency on the pathogenesis of ragweed pollen extract (RWE)-induced allergic asthma in mice and also examined the efficacy of enteral administration of highly specific AR inhibitor, fidarestat.

Methods

The wild type (WT) and AR-/- mice were sensitized and challenged with RWE to induce allergic asthma. AR inhibitor, fidarestat was administered orally. Airway hyper-responsiveness was measured in unrestrained animals using whole body plethysmography. Mucin levels and Th2 cytokine in broncho-alveolar lavage (BAL) were determined using mouse anti-Muc5A/C ELISA kit and multiplex cytokine array, respectively. Eosinophils infiltration and goblet cells were assessed by H&E and periodic acid Schiff (PAS)-staining of formalin-fixed, paraffin-embedded lung sections. T regulatory cells were assessed in spleen derived CD4+CD25+ T cells population.

Results

Deficiency of AR in mice led to significantly decreased PENH, a marker of airway hyper-responsiveness, metaplasia of airway epithelial cells and mucus hyper-secretion following RWE-challenge. This was accompanied by a dramatic decrease in infiltration of eosinophils into sub-epithelium of lung as well as in BAL and release of Th2 cytokines in response to RWE-challenge of AR-/- mice. Further, enteral administration of fidarestat significantly prevented eosinophils infiltration, airway hyper-responsiveness and also markedly increased population of T regulatory (CD4+CD25+FoxP3+) cells as compared to RWE-sensitized and challenged mice not treated with fidarestat.

Conclusion

Our results using AR-/- mice strongly suggest the role of AR in allergic asthma pathogenesis and effectiveness of oral administration of AR inhibitor in RWE-induced asthma in mice supports the use of AR inhibitors in the treatment of allergic asthma.
Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images
Authors: Singan Vasanth R , Jones Thouis R , Curran Kathleen M , Simpson Jeremy C
Published: November 2011

Background

Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial.

Results

We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells.

Conclusions

This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets, including high resolution confocal images, live cell time-lapse recordings, and high-throughput screening data sets.
Lost in folding space? Comparing four variants of the thermodynamic model for RNA secondary structure prediction
Authors: Janssen Stefan , Schudoma Christian , Steger Gerhard , Giegerich Robert
Published: November 2011

Background

Many bioinformatics tools for RNA secondary structure analysis are based on a thermodynamic model of RNA folding. They predict a single, "optimal" structure by free energy minimization, they enumerate near-optimal structures, they compute base pair probabilities and dot plots, representative structures of different abstract shapes, or Boltzmann probabilities of structures and shapes. Although all programs refer to the same physical model, they implement it with considerable variation for different tasks, and little is known about the effects of heuristic assumptions and model simplifications used by the programs on the outcome of the analysis.

Results

We extract four different models of the thermodynamic folding space which underlie the programs RNAFOLD, RNASHAPES, and RNASUBOPT. Their differences lie within the details of the energy model and the granularity of the folding space. We implement probabilistic shape analysis for all models, and introduce the shape probability shift as a robust measure of model similarity. Using four data sets derived from experimentally solved structures, we provide a quantitative evaluation of the model differences.

Conclusions

We find that search space granularity affects the computed shape probabilities less than the over- or underapproximation of free energy by a simplified energy model. Still, the approximations perform similar enough to implementations of the full model to justify their continued use in settings where computational constraints call for simpler algorithms. On the side, we observe that the rarely used level 2 shapes, which predict the complete arrangement of helices, multiloops, internal loops and bulges, include the "true" shape in a rather small number of predicted high probability shapes. This calls for an investigation of new strategies to extract high probability members from the (very large) level 2 shape space of an RNA sequence. We provide implementations of all four models, written in a declarative style that makes them easy to be modified. Based on our study, future work on thermodynamic RNA folding may make a choice of model based on our empirical data. It can take our implementations as a starting point for further program development.
Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis
Authors: Thorsen Kasper , Schepeler Troels , Øster Bodil , Rasmussen Mads H , Vang Søren , Wang Kai , Hansen Kristian Q , Lamy Philippe , Pedersen Jakob Skou , Eller Asger , Mansilla Francisco , Laurila Kirsti , Wiuf Carsten , Laurberg Søren , Dyrskjøt Lars , Ørntoft Torben F , Andersen Claus L
Published: November 2011

Background

Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from alternative promoter usage.

Results

By profiling 108 colorectal samples using exon arrays, we identified nine genes (TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5, and SCIN) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for CHEK1, OSBPL1A, and TCF12 in a subset of these cancer types.

To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both OSBPL1A and TRAK1. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.

Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.

Conclusions

Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and OSBPL1A and TRAK1 were found to be regulated in vitro by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.
Prediction of RNA Polymerase II recruitment, elongation and stalling from histone modification data
Authors: Chen Yun , Jørgensen Mette , Kolde Raivo , Zhao Xiaobei , Parker Brian , Valen Eivind , Wen Jiayu , Sandelin Albin
Published: November 2011

Background

Initiation and elongation of RNA polymerase II (RNAPII) transcription is regulated by both DNA sequence and chromatin signals. Recent breakthroughs make it possible to measure the chromatin state and activity of core promoters genome-wide, but dedicated computational strategies are needed to progress from descriptive annotation of data to quantitative, predictive models.

Results

Here, we describe a computational framework which with high accuracy can predict the locations of core promoters, the amount of recruited RNAPII at the promoter, the amount of elongating RNAPII in the gene body, the mRNA production originating from the promoter and finally also the stalling characteristics of RNAPII by considering both quantitative and spatial features of histone modifications around the transcription start site (TSS).

As the model framework can also pinpoint the signals that are the most influential for prediction, it can be used to infer underlying regulatory biology. For example, we show that the H3K4 di- and tri- methylation signals are strongly predictive for promoter location while the acetylation marks H3K9 and H3K27 are highly important in estimating the promoter usage. All of these four marks are found to be necessary for recruitment of RNAPII but not sufficient for the elongation. We also show that the spatial distributions of histone marks are almost as predictive as the signal strength and that a set of histone marks immediately downstream of the TSS is highly predictive of RNAPII stalling.

Conclusions

In this study we introduce a general framework to accurately predict the level of RNAPII recruitment, elongation, stalling and mRNA expression from chromatin signals. The versatility of the method also makes it ideally suited to investigate other genomic data.
Identification of novel targets for breast cancer by exploring gene switches on a genome scale
Authors: Wu Ming , Liu Li , Chan Christina
Published: November 2011

Background

An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches.

Results

We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER) and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2) is uncovered. We further suggest a likely transcription factor that regulates TACSTD2.

Conclusions

Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype.
Management of asthma in pregnant women by general practitioners: A cross sectional survey
Authors: Lim Angelina S , Stewart Kay , Abramson Michael J , George Johnson
Published: November 2011

Background

Poorly controlled asthma can lead to maternal and fetal complications. Despite the known risks of poorly controlled asthma during pregnancy and the need for stepping up therapy when appropriate, there are concerns that management is suboptimal in primary care.

Our objective was to investigate the management of asthma during pregnancy by general practitioners providing shared maternity care.

Methods

A pre-piloted, anonymous mail survey was sent to all general practitioners (n = 842) involved in shared maternity care at six maternity hospitals in Victoria, Australia. Respondents were asked about their perceived safety of individual asthma medications during pregnancy. Approach to asthma management during pregnancy was further explored using scenarios of pregnant women with stable and deteriorating asthma and poor medication adherence.

Results

Inhaled corticosteroids (ICS) were perceived to be the safest and were the preferred preventive medication in first trimester (74.1%), whilst leukotriene receptor antagonists were the least preferred (2.9%). A quarter (25.8%) of respondents would stop or decrease patients' ICS doses during pregnancy, even when their asthma was well controlled by current therapy. In addition, 12.1% of respondents were not sure how to manage deteriorating asthma during pregnancy and opted to refer to another health professional. Almost half the respondents (48.9%) reported encountering medication nonadherence during pregnancy.

Conclusion

A lack of confidence and/or knowledge among general practitioners in managing deteriorating asthma in pregnancy was observed despite a good understanding of the safety of asthma medications during pregnancy, compliance with evidence-based guidelines in the selection of preventive medications, and self reported good asthma knowledge.
Effects of whole-body vibration on postural control in elderly: a systematic review and meta-analysis
Authors: Rogan Slavko , Hilfiker Roger , Herren Kaspar , Radlinger Lorenz , de Bruin Eling D
Published: November 2011

Background

This systematic review was performed to summarize the current evidence for whole body vibration (WBV) interventions on postural control in elderly.

Methods

English and German language papers in Medline, PEDro, Cinahl and the Cochrane databases were searched. Two reviewers extracted data on patients' characteristics, type of WBV intervention and outcomes. Two independent reviewers rated the methodological quality of these studies. Data were pooled using random-effects meta-analysis.

Results

Fifteen papers reporting quantitative data were included. Results from 15 papers could be pooled for a meta-analysis. The studies involved 933 participants. In 7 studies the authors investigated the effects of vibration plates generating vertical sinusoidal vibrations (VS-WBV) and 7 papers described the use of side-alternating sinusoidal vibrations (SS-WBV). One study investigated both VS-WBV and SS-WBV.

Weak to moderate evidence of an overall effect as a result of VS-WBV and SS-WBV was observed for (a) static balance for post-intervention values with a standardized mean difference (SMD) -0.06, 95% CI -0.31 to 0.18 and for change values SMD -0.26, 95% CI -1.09 to 0.57, and (b) dynamic balance for post-intervention-values SMD -0.34, 95% CI -0.60 to -0.08. For functional balance (c) an overall outcome for post-intervention values with SMD of 0.34, 95% CI -0.19 to 0.87 was found.

Conclusions

The 15 studies reviewed were of moderate methodological quality. In summary, SS-WBV seems to have a beneficial effect on dynamic balance in elderly individuals. However, the current results should be interpreted with caution because of the observed heterogeneity of training parameters and statistical methods. Future studies are warranted to evaluate the effects of WBV on postural control in an elderly population.
A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer
Authors: Garcia-Casado Zaida , Romero Ignacio , Fernandez-Serra Antonio , Rubio Luis , Llopis Francisco , Garcia Ana , Llombart Pilar , Lopez-Guerrero Jose A
Published: November 2011

Background

Germline mutations in either of the two tumor-suppressor genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast and ovarian cancer cases. Most of these mutations consist of deletions, insertions, nonsense mutations, and splice variants, however an increasing number of large genomic rearrangements have been identified in these genes.

Methods

We analysed BRCA1 and BRCA2 genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the BRCA1 deletion by Array CGH.

Results

We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a de novo complete BRCA1 gene deletion in the germinal line. The detected deletion started from the region surrounding the VAT1
locus to the beginning of NBR1 gene, including the RND2, ΨBRCA1, BRCA1 and NBR2 complete genes.

Conclusion

This finding supports the large genomic rearrangement screening of BRCA genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.
Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study
Authors: Zdoukopoulos Nikos , Doxani Chrysa , Messinis Ioannis E , Stefanidis Ioannis , Zintzaras Elias
Published: November 2011

Background

The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin.

Methods

We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia.

Results

The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association.

Conclusions

Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.
A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy
Authors: Retèl Valesca P , van der Molen Lisette , Hilgers Frans JM , Rasch Coen RN , L'Ortye Annemiek AAMHJ , Steuten Lotte MG , van Harten Wim H
Published: November 2011

Background

Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective.

Methods

A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research.

Results

PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty.

Conclusions

Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY).
Hydration studies on the archaeal protein Sso7d using NMR measurements and MD simulations
Authors: Bernini Andrea , Spiga Ottavia , Consonni Roberto , Arosio Ivana , Fusi Paola , Cirri Simone , Guagliardi Annamaria , Niccolai Neri
Published: November 2011

Background

How proteins approach surrounding molecules is fundamental to our understanding of the specific interactions that occur at the surface of proteins. The enhanced surface accessibility of small molecules such as organic solvents and paramagnetic probes to protein binding sites has been observed; however, the molecular basis of this finding has not been fully established. Recently, it has been suggested that hydration dynamics play a predominant role in controlling the distribution of hot spots on surface of proteins.

Results

In the present study, the hydration of the archaeal multifunctional protein Sso7d from Solfolobus solfataricus was investigated using a combination of computational and experimental data derived from molecular dynamics simulations and ePHOGSY NMR spectroscopy.

Conclusions

We obtained a convergent protein hydration landscape that indicated how the shape and stability of the Sso7d hydration shell could modulate the function of the protein. The DNA binding domain overlaps with the protein region involved in chaperon activity and this domain is hydrated only in a very small central region. This localized hydration seems to favor intermolecular approaches from a large variety of ligands. Conversely, high water density was found in surface regions of the protein where the ATP binding site is located, suggesting that surface water molecules play a role in protecting the protein from unspecific interactions.
Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheumatoid arthritis - a potential role for heat shock protein 70
Authors: Moodley Devapregasan , Mody Girish M , Chuturgoon Anil A
Published: November 2011

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL) apoptosis may also be involved in perpetuation of autoimmune processes in RA.

Methods

We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation-induced-cell-death (AICD), PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70) is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots.

Results

The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B-lymphocytes). RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls.

Conclusion

The results suggest that while apoptosis may be initiated in RA-PBLs, they may lack commitment to fully executing the apoptotic program. This may be related to inhibition on apoptotic transduction by HSP70. This study provides evidence that abnormalities in RA-PBLs apoptosis may occur whilst still in circulation and may contribute to pathogenesis of the disease.
Non-blood medical care in gynecologic oncology: a review and update of blood conservation management schemes
Authors: Simou Maria , Thomakos Nikolaos , Zagouri Flora , Vlysmas Antonios , Akrivos Nikolaos , Zacharakis Dimitrios , Papadimitriou Christos A , Dimopoulos Meletios-Athanassios , Rodolakis Alexandros , Antsaklis Aris
Published: November 2011

This review attempts to outline the alternative measures and interventions used in bloodless surgery in the field of gynecologic oncology and demonstrate their effectiveness. Nowadays, as increasingly more patients are expressing their fears concerning the potential risks accompanying allogenic transfusion of blood products, putting the theory of bloodless surgery into practice seems to gaining greater acceptance. An increasing number of institutions appear to be successfully adopting approaches that minimize blood usage for all patients treated for gynecologic malignancies. Preoperative, intraoperative and postoperative measures are required, such as optimization of red blood cell mass, adequate preoperative plan and invasive hemostatic procedures, assisting anesthetic techniques, individualization of anemia tolerance, autologous blood donation, normovolemic hemodilution, intraoperative cell salvage and pharmacologic agents for controlling blood loss. An individualised management plan of experienced personnel adopting a multidisciplinary team approach should be available to establish non-blood management strategies, and not only on demand of the patient, in the field of gynecologic oncology with the use of drugs, devices and surgical-medical techniques.
Modelling ultrasound-induced mild hyperthermia of hyperplasia in vascular grafts
Authors: Brinton Mark R , Stewart Russell J , Cheung Alfred K , Christensen Douglas A , Shiu Yan-Ting E
Published: November 2011

Background

Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over-growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood.

Methods

Ultrasound beams from two transducers (1.5 and 3.2 MHz) were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD) method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL® Multiphysics heat transfer model. 50°C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13°C temperature rise from 37°C in the ePTFE.

Results

Simulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native tissues.

Conclusions

Modelling shows that ultrasound can selectively heat ePTFE grafts and produce temperatures that cause cell death on the graft. The temperature increase in blood is negligible and that in the adjacent soft tissues may be minimized by skin cooling and using appropriate transducers. Therefore, ultrasound heating may have the potential to reduce neointimal hyperplasia and failure of ePTFE vascular grafts.
Cerebellum-specific and age-dependent expression of an endogenous retrovirus with intact coding potential
Authors: Lee Kang-Hoon , Horiuchi Makoto , Itoh Takayuki , Greenhalgh David G , Cho Kiho
Published: November 2011

Background

Endogenous retroviruses (ERVs), including murine leukemia virus (MuLV) type-ERVs (MuLV-ERVs), are presumed to occupy ~10% of the mouse genome. In this study, following the identification of a full-length MuLV-ERV by in silico survey of the C57BL/6J mouse genome, its distribution in different mouse strains and expression characteristics were investigated.

Results

Application of a set of ERV mining protocols identified a MuLV-ERV locus with full coding potential on chromosome 8 (named ERVmch8). It appears that ERVmch8 shares the same genomic locus with a replication-incompetent MuLV-ERV, called Emv2; however, it was not confirmed due to a lack of relevant annotation and Emv2 sequence information. The ERVmch8 sequence was more prevalent in laboratory strains compared to wild-derived strains. Among 16 different tissues of ~12 week-old female C57BL/6J mice, brain homogenate was the only tissue with evident expression of ERVmch8. Further ERVmch8 expression analysis in six different brain compartments and four peripheral neuronal tissues of C57BL/6J mice revealed no significant expression except for the cerebellum in which the ERVmch8 locus' low methylation status was unique compared to the other brain compartments. The ERVmch8 locus was found to be surrounded by genes associated with neuronal development and/or inflammation. Interestingly, cerebellum-specific ERVmch8 expression was age-dependent with almost no expression at 2 weeks and a plateau at 6 weeks.

Conclusions

The ecotropic ERVmch8 locus on the C57BL/6J mouse genome was relatively undermethylated in the cerebellum, and its expression was cerebellum-specific and age-dependent.
A simple and efficient micrografting method for stably transformed Nicotiana attenuata plants to examine shoot-root signaling
Authors: Fragoso Variluska , Goddard Hannah , Baldwin Ian T , Kim Sang-Gyu
Published: November 2011

To adjust their development to the environment, plants rely on specific signals that travel from shoot to root and vice versa. Here we describe an efficient micrografting protocol for Nicotiana attenuata, a useful tool for identifying these signals and understanding their functions. Additionally we analyzed transcript accumulation profiles of scions and rootstocks of grafts performed with wild-type and stably transformed N. attenuata. Our results are consistent with the source-to-sink movement of an sRNA silencing signal.
Overexpression of α-enolase correlates with poor survival in canine mammary carcinoma
Authors: Chu Pei-Yi , Hsu Nicholas C , Liao Albert T , Shih Neng-Yao , Hou Ming-Feng , Liu Chen-Hsuan
Published: November 2011

Background

α-Enolase (ENO1) is a key glycolytic enzyme implicated in the development of many human cancers including breast cancer. Increased expression of ENO1 has recently been reported in estrogen (ER)-positive human breast cancer patients. The present study examined the expression of ENO1 and assessed its significance in canine mammary carcinoma.

Results

Immunohistochemical staining was employed to investigate the expression of ENO1 in 82 cases of canine mammary tumor (32 benign tumors and 50 carcinomas). Quantification of immunohistochemistry was carried out using Quick score and the results showed cytoplasmic ENO1 overexpression in 9 of the 50 carcinomas (18%). Overexpression of ENO1 correlated significantly with shorter cause-specific survival (P = 0.019), but was not associated with ER positivity in canine mammary carcinoma.

Conclusions

Our findings suggest that overexpression of ENO1 may be used as a prognostic marker for poor outcome in canine mammary carcinoma.