bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Molecular Evidence for Association of SLE with parvovirus B19
Authors: Pavlovic M. , Kats A. , Cavallo M. , Shoenfeld Y.
Published: May 2010

In addition to genetic and environmental factors, viruses have been suspected as causes and/or contributors to human autoimmune diseases, although direct evidence for the association is generally lacking. Parvovirus B19, the cause of Fifth disease in childhood, and possible trigger in the spectrum of autoimmune diseases in adults, has emerged as one of the central viral candidates within the last few years. In this article we propose a possible model for parvovirus B19 association with systemic lupus erythematosus (SLE). The basis for our model is the secretion of hydrolyzing anti-ssDNA autoantibodies in 30—70% of cases with SLE, which in turn can either hydrolyze viral B19 ssDNA in blood and other fluids, or intranuclear, replicated viral ssDNA after re-activation and translocation of the virus into the nucleus of the host permissive cells. Both mechanisms contribute to perpetuation and maintenance of a ‘vicious cycle’ with concomitant flares in SLE, and involve inevitable TLR9 sensitization and genetic switch for anti-ssDNA autoantibody production from activated B cells in individuals prone to triggering. This model strongly suggests a major potential impact upon early prevention (vaccination) and targeted therapy of this subclass within the SLE spectrum of diseases. Incorporated in this new concept is an innovative idea for developing the tool for more precise (individualized) diagnosis, prevention, and therapy.
Truth and opinion in climate change discourse: The Gore–Hansen disagreement
Authors: Russill Chris
Published: May 2010

In this paper, I discuss the “inconvenient truth” strategy of Al Gore. I argue that Gore’s notion of truth upholds a conception of science and policy that narrows our understanding of climate change discourse. In one notable exchange, Gore and NASA scientist, James Hansen, disagreed about whether scientific statements based on Hansen’s computer simulations were truth or opinion. This exchange is featured in An Inconvenient Truth, yet the disagreement is edited from the film and presented simply as an instance of Hansen speaking “inconvenient truth.” In this article, I compare the filmic representation of Hansen’s testimony with the congressional record. I place their exchange in a broader historical perspective on climate change disputation in order to discuss the implications of Gore’s perspective on truth.
Modding the History of Science: Values at Play in Modder Discussions of Sid Meier’s CIVILIZATION
Authors: Owens Trevor
Published: May 2010

Sid Meier’s CIVILIZATION has been promoted as an educational tool, used as a platform for building educational simulations, and maligned as promoting Eurocentrism, bioimperialism, and racial superiority. This article explores the complex issues involved in interpreting a game through analysis of the ways modders (gamers who modify the game) have approached the history of science, technology, and knowledge embodied in the game. Through text analysis of modder discussion, this article explores the assumed values and tone of the community’s discourse. The study offers initial findings that CIVILIZATION modders value a variety of positive discursive practices for developing historical models. Community members value a form of historical authenticity, they prize subtlety and nuance in models for science in the game, and they communicate through civil consensus building. Game theorists, players, and scholars, as well as those interested in modeling the history, sociology, and philosophy of science, will be interested to see the ways in which CIVILIZATION III cultivates an audience of modders who spend their time reimagining how science and technology could work in the game.
When I Know Who “We” Are, I Can Be “Me”: The Primary Role of Cultural Identity Clarity for Psychological Well-Being
Authors: Taylor Donald M. , Usborne Esther
Published: May 2010

Collective trauma, be it through colonization (e.g., Aboriginal Peoples), slavery (e.g., African Americans) or war, has a dramatic impact on the psychological well-being of each and every individual member of the collective. Thus, interventions are often conceptualized and delivered at the individual level with a view to minimizing the psychological disequilibrium of each individual. In contrast, we propose a theory of self that emphasizes the primacy of cultural identity for psychological well-being. We present a series of studies that illustrate the importance of cultural identity clarity for personal identity and for psychological well-being. Our theoretical model proposes that interventions aimed at clarifying cultural identity may play a constructive role in the promotion of the well-being of group members exposed to collective trauma.
An exploration of the relationship between self-esteem, health knowledge, chronic dieting and body shape accuracy
Authors: Feero Sara Ann Muir , Steadman Liz
Published: May 2010

Aims: To explore the relationship between self-esteem, health knowledge, chronic dieting and perceived body size and shape.

Method: The study design was cross-sectional in nature; 41 women from diet and health clubs participated by completing a questionnaire containing scales that assessed levels of self-esteem, health knowledge and chronic dieting. They also responded to a body shape accuracy instrument that was designed to measure accurately the percentage of over- or underestimation of body size and shape.

Results: Correlational analyses showed that there was a statistically significant negative relationship between self-esteem and chronic dieting and a significant positive relationship between chronic dieting and health knowledge. Chi squared (χ 2) analysis revealed that women with higher levels of health knowledge had low self-esteem and that low self-esteem women were significantly more likely than women with high self-esteem to underestimate their body size.

Conclusions: Levels of health knowledge and self-esteem appear to play a complex role in chronic dieting and subjective perceptions of body shape and it is an area that warrants further investigation. The body shape scale proved to be a successful instrument and further trials using this scale are recommended.
Working as a community food worker: Voices from the inside
Authors: Coufopoulos Anne , Coffey Margaret , Dugdill Lindsey
Published: May 2010

Aims: Community food worker (CFW) is one of the new roles that were proposed in the 2004 White Paper Choosing Health: Making Healthier Choices Easier. CFWs are recruited from local communities and generally operate in areas characterized by extreme social deprivation. The aim of this paper is to illuminate the experience of being a CFW in the context of working in a relatively new non-professional role.

Methods: As part of an ongoing evaluation of a CFW scheme in the north west of England, a qualitative interview and two focus groups were conducted with CFWs. Thematic analysis of the data was undertaken.

Results: Emergent issues faced by these new practitioners include: the nature of their role; quantifying success; working with other health professionals; skills and knowledge; and strategies used to work with communities.

Conclusion: This study has highlighted some pertinent and previously unreported issues related to the experience of being a CFW, raising questions about their assimilation into the public health workforce and their use in delivering effective public health interventions without further integration.
Effect of Mg/nano-Al2O3 interaction time during stirring on microstructure and mechanical properties of Mg–Al2O3 composite
Authors: Shanthi M , Xia G L X , Gupta M
Published: May 2010

In the present study, magnesium based composites containing 1·1 vol. of alumina particulates at nanolength scale were synthesised using disintegrated melt deposition technique. The main focus was to vary interaction time between molten magnesium and nano-Al2O3 particulates during stirring and to study its effects on the microstructure and mechanical properties. With an increase in stirring time, microstructural characterisation of the composite materials revealed reasonably uniform distribution of Al2O3 reinforcement, marginal grain refinement and presence of minimal porosity. Mechanical properties characterisation revealed that an increase in stirring time led to a simultaneous increase in hardness, 0·2 yield strength and ultimate tensile strength while ductility was compromised beyond 7·5 min stirring when compared to pure Mg. The optimal stirring time is observed to be in 5–7·5 min range in order to realise the best combination of strength, hardness, ductility and work of fracture.
Microstructure development in resistance spot welded galvannealed IF steel sheet
Authors: Chakraborty G. , Pal T. K. , Shome M.
Published: May 2010

Interstitial free (IF) steels having excellent drawing and forming characteristics find extensive use in autobody panels. Although, resistance spot welded joints are widely used in the automobile industry, little is known about the metallurgical changes which occur during the spot welding process. The investigation of the metallurgical changes is very important for the safety strength of the welded joints. In the present research work, microstructures of the different zones of spot welded interstitial free steels have been characterised by optical, scanning electron and transmission electron microscopes. Microstructural changes at weld and heat affected zone have also been correlated with welding heat input and microhardness values.
Stat5a serine 725 and 779 phosphorylation is a prerequisite for hematopoietic transformation
Authors: Friedbichler Katrin , Kerenyi Marc A. , Kovacic Boris , Li Geqiang , Hoelbl Andrea , Yahiaoui Saliha , Sexl Veronika , Müllner Ernst W. , Fajmann Sabine , Cerny-Reiterer Sabine , Valent Peter , Beug Hartmut , Gouilleux Fabrice , Bunting Kevin D. , Moriggl Richard
Published: May 2010

Stat5 transcription factors are essential gene regulators promoting proliferation, survival, and differentiation of all hematopoietic cell types. Mutations or fusions of oncogenic tyrosine kinases often result in constitutive Stat5 activation. We have modeled persistent Stat5 activity by using an oncogenic Stat5a variant (cS5). To analyze the hitherto unrecognized role of Stat5 serine phosphorylation in this context, we have generated cS5 constructs with mutated C-terminal serines 725 and 779, either alone or in combination. Genetic complementation assays in primary Stat5null/null mast cells and Stat5ΔN T cells demonstrated reconstitution of proliferation with these mutants. Similarly, an in vivo reconstitution experiment of transduced Stat5null/null fetal liver cells transplanted into irradiated wild-type recipients revealed that these mutants exhibit biologic activity in lineage differentiation. By contrast, the leukemogenic potential of cS5 in bone marrow transplants decreased dramatically in cS5 single-serine mutants or was completely absent upon loss of both serine phosphorylation sites. Our data suggest that Stat5a serine phosphorylation is a prerequisite for cS5-mediated leukemogenesis. Hence, interference with Stat5a serine phosphorylation might provide a new therapeutic option for leukemia and myeloid dysplasias without affecting major functions of Stat5 in normal hematopoiesis.
Scavenger receptor BI modulates platelet reactivity and thrombosis in dyslipidemia
Authors: Ma Yi , Ashraf Mohammad Z. , Podrez Eugene A.
Published: May 2010

Hypercholesterolemia is associated with increased platelet sensitivity to agonists and a prothrombotic phenotype. Mechanisms of platelet hypersensitivity are poorly understood; however, increased platelet cholesterol levels associated with hypercholesterolemia were proposed as leading to hypersensitivity. Scavenger receptor class B type I (SR-BI) in the liver controls plasma high-density lipoprotein (HDL) levels, and SR-BI–deficient mice display a profound dyslipoproteinemia. SR-BI is also expressed on platelets, and recent studies have suggested a role for SR-BI in platelet function; however, its role in hemostasis is unknown. Our present studies demonstrated that non-bone marrow–derived SR-BI deficiency and the dyslipidemia associated with it lead to platelet hyperreactivity that was mechanistically linked to increased platelet cholesterol content. Platelet-specific deficiency of SR-BI, on the other hand, was associated with resistance to hyperreactivity induced by increased platelet cholesterol content. Intravital thrombosis studies demonstrated that platelet SR-BI deficiency protected mice from prothrombotic phenotype in 2 types of dyslipidemia associated with increased platelet cholesterol content. These novel findings demonstrate that SR-BI plays dual roles in thrombosis and may contribute to acute cardiovascular events in vivo in hypercholesterolemia.
TargetSpy: a supervised machine learning approach for microRNA target prediction
Authors: Sturm Martin , Hackenberg Michael , Langenberger David , Frishman Dmitrij
Published: May 2010

Background

Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites.

Results

We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.

In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms.

Conclusion

Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila, suggesting that it may be applicable to a broad range of species. Moreover, we have demonstrated that the application of machine learning techniques in combination with upcoming deep sequencing data results in a powerful microRNA target site prediction tool http://www.targetspy.org.
Identification of the heart as the critical site of adenosine mediated embryo protection
Authors: Wendler Christopher C , Poulsen Ryan R , Ghatpande Satish , Greene Robert W , Rivkees Scott A
Published: May 2010

Background

Our understanding of the mechanisms that protect the developing embryo from intrauterine stress is limited. Recently, adenosine has been demonstrated to play a critical role in protecting the embryo against hypoxia via adenosine A1 receptors (A1ARs), which are expressed in the heart, nervous system, and other sites during development. However, the sites of A1AR action that mediate embryo protection are not known. To determine if the heart is a key site of adenosine-mediated embryo protection, A1ARs were selectively deleted in the embryonic heart using a Cre-LoxP system in which the alpha-myosin heavy chain promoter drives Cre-recombinase expression and excision of the A1AR gene from cardiomyocytes.

Results

With increasing exposure of maternal hypoxia (10% O2) from 48-96 hours beginning at embryonic day (E) 8.5, embryo viability decreased in the cardiac-A1AR deleted embryos. 48 hours of hypoxia reduced embryonic viability by 49% in embryos exposed from E10.5-12.5 but no effect on viability was observed in younger embryos exposed to hypoxia from E8.5-10.5. After 72 hours of hypoxia, 57.8% of the cardiac-A1AR deleted embryos were either dead or re-absorbed compared to 13.7% of control littermates and after 96 hours 81.6% of cardiac-A1AR deleted embryos were dead or re-absorbed. After 72 hours of hypoxia, cardiac size was reduced significantly more in the cardiac-A1AR deleted hearts compared to controls. Gene expression analysis revealed clusters of genes that are regulated by both hypoxia and A1AR expression.

Conclusions

These data identify the embryonic heart as the critical site where adenosine acts to protect the embryo against hypoxia. As such these studies identify a previously unrecognized mechanism of embryo protection.
Prevalence of Borrelia burgdorferi sensu lato in rodents from Gansu, northwestern China
Authors: Zhang Fang , Gong Zhanwei , Zhang Jijun , Liu Zengjia
Published: May 2010

Background

Lyme disease is a multi-organ infection disease caused by Borrelia burgdorferi sensu lato. Lyme disease was first documented in north-east China in 1986. Since then more than 20 provinces in China were confirmed the existence of nature foci of Lyme disease. In the present study, a molecular epidemiological survey was conducted to investigate the presence of Borrelia burgdorferi sensu lato in rodents from Gansu Province for the first time.

Result

A total of 140 rodents of 7 species were examined for Borrelia burgdorferi sensu lato. by nested-PCR and culture isolation. The overall infection rate was 22.86%. Two rodent species most frequently trapped were responsible for all positive. 3 strains were isolated from Apodemus agrarius, which belonged to B. garinii, 1 strain isolated from Rattus losea was identified as B. afzelii.

Conclusion

The study firstly showed the role of rodents in maintaining the pathogen of Lyme disease in the environment from Gansu Province and there existed at least two genotypes of Lyme disease spirochaetes in rodents.
Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia
Authors: Alves Brunna E , Montalvao Silmara AL , Aranha Franciso JP , Siegl Tania FG , Souza Carmino A , Lorand-Metze Irene , Annichino-Bizzacchi Joyce M , De Paula Erich V
Published: May 2010

Background

Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units.

Methods

We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications.

Results

Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores.

Conclusions

Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.
Effect of BRCA2 sequence variants predicted to disrupt exonic splice enhancers on BRCA2transcripts
Authors: Whiley Phillip J , Pettigrew Christopher A , Brewster Brooke L , Walker Logan C ,   kConFab Investigators, Spurdle Amanda B , Brown Melissa A
Published: May 2010

Background

Genetic screening of breast cancer patients and their families have identified a number of variants of unknown clinical significance in the breast cancer susceptibility genes, BRCA1 and BRCA2. Evaluation of such unclassified variants may be assisted by web-based bioinformatic prediction tools, although accurate prediction of aberrant splicing by unclassified variants affecting exonic splice enhancers (ESEs) remains a challenge.

Methods

This study used a combination of RT-PCR analysis and splicing reporter minigene assays to assess five unclassified variants in the BRCA2 gene that we had previously predicted to disrupt an ESE using bioinformatic approaches.

Results

Analysis of BRCA2 c.8308 G > A (p.Ala2770Thr) by mRNA analysis, and BRCA2 c.8962A > G (p.Ser2988Gly), BRCA2 c.8972G > A (p.Arg2991His), BRCA2 c.9172A > G (p.Ser3058Gly), and BRCA2 c.9213G > T (p.Glu3071Asp) by a minigene assay, revealed no evidence for aberrant splicing.

Conclusions

These results illustrate the need for improved methods for predicting functional ESEs and the potential consequences of sequence variants contained therein.
Identification of valid reference genes for gene expression studies of human stomach cancer by reverse transcription-qPCR
Authors: Rho Hyun-Wook , Lee Byoung-Chan , Choi Eun-Seok , Choi Il-Ju , Lee Yeon-Su , Goh Sung-Ho
Published: May 2010

Background

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a powerful method for the analysis of gene expression. Target gene expression levels are usually normalized to a consistently expressed reference gene also known as internal standard, in the same sample. However, much effort has not been expended thus far in the search for reference genes suitable for the study of stomach cancer using RT-qPCR, although selection of optimal reference genes is critical for interpretation of results.

Methods

We assessed the suitability of six possible reference genes, beta-actin (ACTB), glyceraldehydes-3-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyl transferase 1 (HPRT1), beta-2-microglobulin (B2M), ribosomal subunit L29 (RPL29) and 18S ribosomal RNA (18S rRNA) in 20 normal and tumor stomach tissue pairs of stomach cancer patients and 6 stomach cancer cell lines, by RT-qPCR. Employing expression stability analyses using NormFinder and geNorm algorithms we determined the order of performance of these reference genes and their variation values.

Results

This RT-qPCR study showed that there are statistically significant (p < 0.05) differences in the expression levels of HPRT1 and 18S rRNA in 'normal-' versus 'tumor stomach tissues'. The stability analyses by geNorm suggest B2M-GAPDH, as best reference gene combination for 'stomach cancer cell lines'; RPL29-HPRT1, for 'all stomach tissues'; and ACTB-18S rRNA, for 'all stomach cell lines and tissues'. NormFinder also identified B2M as the best reference gene for 'stomach cancer cell lines', RPL29-B2M for 'all stomach tissues', and 18S rRNA-ACTB for 'all stomach cell lines and tissues'. The comparisons of normalized expression of the target gene, GPNMB, showed different interpretation of target gene expression depend on best single reference gene or combination.

Conclusion

This study validated RPL29 and RPL29-B2M as the best single reference genes and combination, for RT-qPCR analysis of 'all stomach tissues', and B2M and B2M-GAPDH as the best single reference gene and combination, for 'stomach cancer cell lines'. Use of these validated reference genes should provide more exact interpretation of differential gene expressions at transcription level in stomach cancer.
Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis
Authors: Kim Jong-Hyuk , Yu Chi-Ho , Yhee Ji-Young , Im Keum-Soon , Kim Na-Hyun , Sur Jung-Hyang
Published: May 2010

Background

Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels.

Methods

Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses.

Results

The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion.

Conclusion

In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although metastasis of canine seminomas has rarely been reported, our results support that canine SE could have high metastatic potential similar to the human counterpart. Further studies are required to clarify the relationship between canine SE and clinical data with metastatic factors.
Why Iranian married women use withdrawal instead of oral contraceptives? A qualitative study from Iran
Authors: Rahnama Parvin , Hidarnia Alireza , Shokravi Farkhondeh Amin , Kazemnejad Anoushiravan , Oakley Deborah , Montazeri Ali
Published: May 2010

Background

Withdrawal as a method of birth control is still used in Iran. The aim of this study was to explore married women's perspectives and attitudes on withdrawal use instead of oral contraceptive (OC) in Tehran, Iran.

Methods

This was a qualitative study. Participants were 50 married women, not currently pregnant, not desiring pregnancy and who had been using withdrawal for contraception. Face-to face interviews were conducted to collect data. Content analysis was performed to analyze the data.

Results

Four major themes were extracted from the interviews: advantages, disadvantages, barriers for OC use, and husband-related factors. Advantages of withdrawal use were identified as: easy to use, convenient, ease of access, natural. Even those participants who had experienced unwanted pregnancy while using withdrawal, relied on withdrawal as their contraceptive method. Disadvantages of OC included concerns about side effects. Barriers related to use of OC included the need for medical advice, vaginal examination and daily use. Husband-related factors included: the husband wanted to be the primary decision maker on the number of children and that he preferred withdrawal.

Conclusion

Health providers should address misunderstandings that exist about OC and highlight the non-contraceptive health benefits of OC to balance the information provided for women. We suggest that not only women but also their spouses be advised in family planning programs.
MRC chronic Dyspnea Scale: Relationships with cardiopulmonary exercise testing and 6-minute walk test in idiopathic pulmonary fibrosis patients: a prospective study
Authors: Manali Effrosyni D , Lyberopoulos Panagiotis , Triantafillidou Christina , Kolilekas Likourgos F , Sotiropoulou Christina , Milic-Emili Joseph , Roussos Charis , Papiris Spyros A
Published: May 2010

Background

Exertional dyspnea is the most prominent and disabling feature in idiopathic pulmonary fibrosis (IPF). The Medical Research Chronic (MRC) chronic dyspnea score as well as physiological measurements obtained during cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) are shown to provide information on the severity and survival of disease.

Methods

We prospectively recruited IPF patients and examined the relationship between the MRC score and either CPET or 6MWT parameters known to reflect physiologic derangements limiting exercise capacity in IPF patients

Results

Twenty-five patients with IPF were included in the study. Significant correlations were found between the MRC score and the distance (r = -.781, p < 0.001), the SPO2 at the initiation and the end (r = -.542, p = 0.005 and r = -.713, p < 0.001 respectively) and the desaturation index (r = .634, p = 0.001) for the 6MWT; the MRC score and VO2 peak/kg (r = -.731, p < 0.001), SPO2 at peak exercise (r = -. 682, p < 0.001), VE/VCO2 slope (r = .731, p < 0.001), VE/VCO2 at AT (r = .630, p = 0.002) and the Borg scale at peak exercise (r = .50, p = 0.01) for the CPET. In multiple logistic regression analysis, the only variable independently related to the MRC is the distance walked at the 6MWT.

Conclusion

In this population of IPF patients a good correlation was found between the MRC chronic dyspnoea score and physiological parameters obtained during maximal and submaximal exercise testing known to reflect ventilatory impairment and exercise limitation as well as disease severity and survival. This finding is described for the first time in the literature in this group of patients as far as we know and could explain why a simple chronic dyspnea score provides reliable prognostic information on IPF.
Gel-type autologous chondrocyte (Chondron™) implantation for treatment of articular cartilage defects of the knee
Authors: Choi Nam-Yong , Kim Byoung-Woo , Yeo Woo-Jin , Kim Haeng-Boo , Suh Dong-Sam , Kim Jin-Soo , Kim Yoon-Sik , Seo Yong-Ho , Cho Jea-Yeong , Chun Chung-Woo , Park Hyun-Shin , Shetty Asode Ananthram , Kim Seok-Jung
Published: May 2010

Background

Gel-type autologous chondrocyte (Chondron™) implantations have been used for several years without using periosteum or membrane. This study involves evaluations of the clinical results of Chondron™ at many clinical centers at various time points during the postoperative patient follow-up.

Methods

Data from 98 patients with articular cartilage injury of the knee joint and who underwent Chondron™ implantation at ten Korean hospitals between January 2005 and November 2008, were included and were divided into two groups based on the patient follow-up period, i.e. 13~24-month follow-up and greater than 25-month follow-up. The telephone Knee Society Score obtained during telephone interviews with patients, was used as the evaluation tool.

Results

On the tKSS-A (telephone Knee Society Score-A), the score improved from 43.52 ± 20.20 to 89.71 ± 13.69 (P < 0.05), and on the tKSS-B (telephone Knee Society Score-B), the score improved from 50.66 ± 20.05 to 89.38 ± 15.76 (P < 0.05). The total improvement was from 94.18 ± 31.43 to 179.10 ± 24.69 (P < 0.05).

Conclusion

Gel-type autologous chondrocyte implantation for chondral knee defects appears to be a safe and effective method for both decreasing pain and improving knee function.
Influence of arthritis and non-arthritis related factors on areal bone mineral density (BMDa) in women with longstanding inflammatory polyarthritis: a primary care based inception cohort
Authors: Pye Stephen R , Marshall Tarnya , Gaffney Karl , Silman Alan J , Symmons Deborah PM , O'Neill Terence W
Published: May 2010

Background

The aim of this analysis was to determine the relative influence of disease and non-disease factors on areal bone mineral density (BMDa) in a primary care based cohort of women with inflammatory polyarthritis.

Methods

Women aged 16 years and over with recent onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1993. Subjects were examined at both baseline and follow up for the presence of tender, swollen and deformed joints. At the 10th anniversary visit, a sub-sample of women were invited to complete a bone health questionnaire and attend for BMDa (Hologic, QDR 4000). Linear regression was used to examine the association between BMDa with both (i) arthritis-related factors assessed at baseline and the 10th anniversary visit and (ii) standard risk factors for osteoporosis. Adjustments were made for age.

Results

108 women, mean age 58.0 years were studied. Older age, decreasing weight and BMI at follow up were all associated with lower BMDa at both the spine and femoral neck. None of the lifestyle factors were linked. Indices of joint damage including 10th anniversary deformed joint count and erosive joint count were the arthritis-related variables linked with a reduction in BMDa at the femoral neck. By contrast, disease activity as determined by the number of tender and or swollen joints assessed both at baseline and follow up was not linked with BMDa at either site.

Conclusion

Cumulative disease damage was the strongest predictor of reduced femoral bone density. Other disease and lifestyle factors have only a modest influence.
Genetic inactivation of the Fanconi anemia gene FANCC identified in the hepatocellular carcinoma cell line HuH-7 confers sensitivity towards DNA-interstrand crosslinking agents
Authors: Palagyi Andreas , Neveling Kornelia , Plinninger Ursula , Ziesch Andreas , Targosz Bianca-Sabrina , Denk Gerald U , Ochs Stephanie , Rizzani Antonia , Meier Daniel , Thasler Wolfgang E , Hanenberg Helmut , De Toni Enrico N , Bassermann Florian , Schäfer Claus , Göke Burkhard , Schindler Detlev , Gallmeier Eike
Published: May 2010

Background

Inactivation of the Fanconi anemia (FA) pathway through defects in one of 13 FA genes occurs at low frequency in various solid cancer entities among the general population. As FA pathway inactivation confers a distinct hypersensitivity towards DNA interstrand-crosslinking (ICL)-agents, FA defects represent rational targets for individualized therapeutic strategies. Except for pancreatic cancer, however, the prevalence of FA defects in gastrointestinal (GI) tumors has not yet been systematically explored.

Results

A panel of GI cancer cell lines was screened for FA pathway inactivation applying FANCD2 monoubiquitination and FANCD2/RAD51 nuclear focus formation and a newly identified FA pathway-deficient cell line was functionally characterized. The hepatocellular carcinoma (HCC) line HuH-7 was defective in FANCD2 monoubiquitination and FANCD2 nuclear focus formation but proficient in RAD51 focus formation. Gene complementation studies revealed that this proximal FA pathway inactivation was attributable to defective FANCC function in HuH-7 cells. Accordingly, a homozygous inactivatingFANCCnonsense mutation (c.553C > T, p.R185X) was identified in HuH-7, resulting in partial transcriptional skipping of exon 6 and leading to the classic cellular FA hypersensitivity phenotype; HuH-7 cells exhibited a strongly reduced proliferation rate and a pronounced G2 cell cycle arrest at distinctly lower concentrations of ICL-agents than a panel of non-isogenic, FA pathway-proficient HCC cell lines. Upon retroviral transduction of HuH-7 cells withFANCCcDNA, FA pathway functions were restored and ICL-hypersensitivity abrogated. Analyses of 18 surgical HCC specimens yielded no further examples for genetic or epigenetic inactivation ofFANCC,FANCF, orFANCGin HCC, suggesting a low prevalence of proximal FA pathway inactivation in this tumor type.

Conclusions

As the majority of HCC are chemoresistant, assessment of FA pathway function in HCC could identify small subpopulations of patients expected to predictably benefit from individualized treatment protocols using ICL-agents.
TGFBI expression is associated with a better response to chemotherapy in NSCLC
Authors: Irigoyen Marta , Pajares María J , Agorreta Jackeline , Ponz-Sarvisé Mariano , Salvo Elisabeth , Lozano María D , Pío Ruben , Gil-Bazo Ignacio , Rouzaut Ana
Published: May 2010

Background

Lung cancer is one of the most prevalent neoplasias in developed countries. Advances in patient survival have been limited and the identification of prognostic molecules is needed. Resistance to treatment is strongly related to tumor cell adhesion to the extracellular matrix and alterations in the quantity and nature of molecules constituting the tumor cell niche. Recently, transforming growth factor beta-induced protein (TGFBI), an extracellular matrix adaptor protein, has been reported to be differentially expressed in transformed tissues. Loss of TGFBI expression has been described in several cancers including lung carcinoma, and it has been suggested to act as a tumor suppressor gene.

Results

To address the importance of TGFBI expression in cancer progression, we determined its expression in NSCLC clinical samples using immunohistochemistry. We identified a strong association between elevated TGFBI expression and the response to chemotherapy. Furthermore, we transiently over-expressed and silenced TGFBI in human NSCLC cell lines. Cells over-expressing TGFBI displayed increased sensitivity to etoposide, paclitaxel, cisplatin and gemcitabine. We observed that TGFBI-mediated induction of apoptosis occurred through its binding to αvβ3 integrin. We also determined that full-length TGFBI did not induce caspase 3/7 activation but its proteolytic fragments that were < 3 kDa in size, were able to activate caspase 3, 7 and 8. This pro-apoptotic effect was blocked by anti-αvβ3 integrin antibodies.

Conclusions

The results shown here indicate that TGFBI is a predictive factor of the response to chemotherapy, and suggest the use of TGFBI-derived peptides as possible therapeutic adjuvants for the enhancement of responses to chemotherapy.
Differential Adeno-Associated Virus Mediated Gene Transfer to Sensory Neurons following Intrathecal Delivery by Direct Lumbar Puncture
Authors: Vulchanova Lucy , Schuster Daniel J , Belur Lalitha R , Riedl Maureen S , Podetz-Pedersen Kelly M , Kitto Kelley F , Wilcox George L , McIvor R Scott , Fairbanks Carolyn A
Published: May 2010

Background:

Neuronal transduction by adeno-associated viral (AAV) vectors has been demonstrated in cortex, brainstem, cerebellum, and sensory ganglia. Intrathecal delivery of AAV serotypes that transduce neurons in dorsal root ganglia (DRG) and spinal cord offers substantial opportunities to 1) further study mechanisms underlying chronic pain, and 2) develop novel gene-based therapies for the treatment and management of chronic pain using a non-invasive delivery route with established safety margins. In this study we have compared expression patterns of AAV serotype 5 (AAV5)- and AAV serotype 8 (AAV8)-mediated gene transfer to sensory neurons following intrathecal delivery by direct lumbar puncture.

Results:

Intravenous mannitol pre-treatment significantly enhanced transduction of primary sensory neurons after direct lumbar puncture injection of AAV5 (rAAV5-GFP) or AAV8 (rAAV8-GFP) carrying the green fluorescent protein (GFP) gene. The presence of GFP in DRG neurons was consistent with the following evidence for primary afferent origin of the majority of GFP-positive fibers in spinal cord: 1) GFP-positive axons were evident in both dorsal roots and dorsal columns; and 2) dorsal rhizotomy, which severs the primary afferent input to spinal cord, abolished the majority of GFP labeling in dorsal horn. We found that both rAAV5-GFP and rAAV8-GFP appear to preferentially target large-diameter DRG neurons, while excluding the isolectin-B4 (IB4) -binding population of small diameter neurons. In addition, a larger proportion of CGRP-positive cells was transduced by rAAV5-GFP, compared to rAAV8-GFP.

Conclusions:

The present study demonstrates the feasibility of minimally invasive gene transfer to sensory neurons using direct lumbar puncture and provides evidence for differential targeting of subtypes of DRG neurons by AAV vectors.
Efficacy of n-3 polyunsaturated fatty acids and feasibility of optimizing preventive strategies in patients at high cardiovascular risk: rationale, design and baseline characteristics of the Rischio and Prevenzione study, a large randomised trial in general practice
Authors:   Rischio and Prevenzione Investigators
Published: May 2010

Background

The optimization of preventive strategies in patients at high risk of cardiovascular events and the evaluation of bottlenecks and limitations of transferring current guidelines to the real world of clinical practice are important limiting steps to cardiovascular prevention. Treatment with n-3 polyunsaturated fatty acids improves prognosis after myocardial infarction, but evidence of this benefit is lacking in patients at high cardiovascular risk, but without a history of myocardial infarction.

Methods/design

Patients were eligible if their general practitioner (GP) considered them at high cardiovascular risk because of a cardiovascular disease other than myocardial infarction, or multiple risk factors (at least four major risk factors in non-diabetic patients and one in diabetics).

Patients were randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily) or placebo in a double-blind study and followed up for five years by their GPs to assess the efficacy of the treatment in preventing cardiovascular mortality (including sudden death) and hospitalization for cardiovascular reasons. The secondary, epidemiological, aim of the study is to assess whether it is feasible to adopt current guidelines in everyday clinical practice, with a view to optimizing all the available preventive strategies in people at high cardiovascular risk.

A nation-wide network of 860 GPs admitted 12,513 patients to the study between February 2004 and March 2007. The mean age was 64 years and 62% were males. Diabetes mellitus plus one or more cardiovascular risk factors was the main inclusion criterion (47%). About 30% of patients were included because of a history of atherosclerotic cardiovascular disease, 21% for four or more risk factors, and less than 1% for other reasons.

Discussion

The Rischio and Prevenzione (R&P) project provides a feasible model to test the efficacy of n-3 polyunsaturated fatty acid therapy in patients at high cardiovascular risk with no history of myocardial infarction, and to assess how to implement recommended preventive strategies in general practice.

Trial registration

ClinicalTrials.gov NCT00317707
Expression of the disease on female carriers of X-linked lysosomal disorders: a brief review
Authors: Pinto Louise LC , Vieira Taiane A , Giugliani Roberto , Schwartz Ida VD
Published: May 2010

Most lysosomal diseases (LD) are inherited as autosomal recessive traits, but two important conditions have X-linked inheritance: Fabry disease and Mucopolysaccharidosis II (MPS II). These two diseases show a very different pattern regarding expression on heterozygotes, which does not seem to be explained by the X-inactivation mechanism only. While MPS II heterozygotes are asymptomatic in most instances, in Fabry disease most of female carriers show some disease manifestation, which is sometimes severe. It is known that there is a major difference among X-linked diseases depending on the cell autonomy of the gene product involved and, therefore, on the occurrence of cross-correction. Since lysosomal enzymes are usually secreted and uptaken by neighbor cells, the different findings between MPS II and Fabry disease heterozygotes can also be due to different efficiency of cross-correction (higher in MPS II and lower in Fabry disease). In this paper, we review these two X-linked LD in order to discuss the mechanisms that could explain the different rates of penetrance and expressivity observed in the heterozygotes; this could be helpful to better understand the expression of X-linked traits.
Severed Voices: Radio and the Mediation of Trauma in the Eichmann Trial
Authors: Pinchevski Amit , Liebes Tamar
Published: May 2010

This essay considers the role of the radio in the mediation of trauma during the 1961 Eichmann trial. It is argued that radio broadcasts from the courtroom occasioned a transformation in the status of Holocaust survivors in Israel, who had been previously seen as deeply traumatized, unable or unwilling to speak about their experiences. Taking to the airwaves facilitated a shift in the conditions by which survivors' testimonies could find public articulation. As such, the Eichmann trial provides a compelling case of the significance of media in transforming private traumas into a collective or cultural trauma.
The Blocked Gaze: A User's Guide to Photographing the Separation Barrier-Wall
Authors: Wigoder Meir
Published: May 2010

Meir Wigoder's account of photographing the Separation-Wall, in Israel-Palestine, over a period of three years, offers a critique of the very vigilant and testimonial activity of taking on such projects: Is it possible to de-materialize a wall through a political aesthetic activity? What is the difference between the photographic and the cinematic approaches to recording the construction of such a wall? What role does the vigilant photographer play in insisting on returning to the same locations over and over again? Such questions lead to larger moral, political, and social readings of the role that the wall plays in the Israeli-Palestinian conflict.
LeBron James and the Protocol of Display
Authors: Ommen Brett
Published: May 2010

As visual images increasingly cover the façade of social space and public life, the utility of these surfaces-of-display must be examined beyond displayed content. The preponderance of surfaces says something about the publics that stand before the invitation of visual communication. Before an encounter with content, there is the encounter with surface. As the Nike, Inc. advertising campaign “Chamber of Fear” reveals, that encounter serves a vital purpose in the relationship between publicity and visual communication.
Looking through Coca-Cola: Global Icons and the Popular
Authors: Ghosh Bishnupriya
Published: May 2010

The essay analyzes a 2002 anti-Coca Cola struggle in Plachimada, a village in South India, that mushroomed into a coalition of demands on resource extraction, health, and regulated foreign investments by 2004. The primary focus is on the expressive play with symbols necessary for the very constitution of the popular. Daily rituals around the Coca Cola logo (placing empty plastic pots as mute witness to water scarcity) became critical to the formation of such a front against the corporate giant. I argue such performances are the norm these days in our highly media-saturated environments, motivating this inquiry into the potentialities of mass media—especially familiar icons that provide a ready palette of signifiers for improvisatory ensembles—in forging the popular.