bluuebunny/crossref_metadata_2025 huggingface dataset:
Women Smugglers of Naxalbari
Authors: Lahiri Amlan
Published: June 2010

Poverty forces women to take up any work that is available. In North Bengal, India, many women work as ‘carriers’ for smugglers in the areas bordering Nepal. This article is a brief account of the women who transgress community norms to earn a little money in an unconventional economic activity.
Labour Regulation and Employment Dynamics at the State Level in India
Authors: Dougherty Sean M.
Published: June 2010

India’s federal and state-level labour regulations are evaluated using a set of standardised tools. Though federal labour regulations are found to be highly restrictive in international comparison with OECD countries, there is considerable variation in the regulatory stance in individual Indian states. This variation in regulation is associated with a substantial degree of de facto job flexibility in the states that have undertaken more labour reforms, and less flexibility in those states and sub-sectors that have undertaken fewer reforms. Labour market reforms could serve to limit the detrimental effects that the consequentially high labour costs and rigidity have on the dynamism of the labour market, as well as to improve the labour wage share, limit the relative increase in informal employment and also enhance aggregate productivity.
Co-creating stories: Collaborative experiments in storytelling
Authors: Gabriel Yiannis , Connell N.A.D. (Con)
Published: June 2010

This article reports on an experiment in collaborative storytelling inspired by the Japanese art of ‘renga’. A renga consists of several stanzas, each composed by a different poet, each seeking to find his/her own voice within a text that is jointly created and jointly owned. The chemist Djerassi has argued that by co-creating a prose version of the renga, a community of practitioners can explore dilemmas and views that would be unacceptable otherwise. He refers to this genre as ‘science-in-fiction’—one in which fiction offers licence to address potentially embarrassing, dangerous or taboo topics. Following Djerassi’s approach, the authors coordinated two rengas composed by groups of scholars interested in using stories to research social reality. The article analyses these two rengas, linking them to the genre of fictionalized ethnography pioneered in organizational studies by Watson and Czarniawska. It also discusses the pedagogic potential of such stories as vehicles of management learning.
Leadership and trust: Their effect on knowledge sharing and team performance
Authors: Lee Pauline , Gillespie Nicole , Mann Leon , Wearing Alexander
Published: June 2010

Team leaders who facilitate knowledge sharing and engender trust contribute to team effectiveness. While the separate effects of leadership, trust and knowledge sharing on team performance are well documented, few scholars have investigated the specific links between these factors. This study examines the relationship between the leader as the knowledge builder, trust in the leader and in the team, knowledge sharing and team performance. Surveys were collected from 34 engineering project teams ( n=166 team members, 30 team leaders) and 18 managers in a large automotive organization. The results indicate that by building the team’s expertise, leaders enhance team members’ willingness to rely on and disclose information in the team, which in turn increases team knowledge sharing. Team knowledge sharing significantly predicted leaders’ and managers’ ratings of team performance. The theoretical and practical implications of the findings are discussed.
Chronic atherosclerotic mesenteric ischemia (CMI)
Authors: Zeller Thomas , Rastan Aljoscha , Sixt Sebastian
Published: June 2010

Chronic mesenteric ischemia (CMI) is most likely caused by atherosclerosis and less frequently by external compression and vasculitis. Symptomatic CMI is an uncommon, potentially under-diagnosed condition caused by fixed stenoses or occlusion of, in most conditions, at least two visceral arteries. If only one of the three major bowel-providing arteries — the celiac trunk, and the superior and inferior mesenteric arteries — is affected, the patient is usually asymptomatic due to a tight collateral network. The only exception is the celiac artery compression syndrome which represents primarily a compression syndrome of celiac plexus nerves by the arcuate ligament in conjunction with a compression of the celiac trunk. CMI of atherosclerotic origin is associated with a high morbidity and mortality. During the last decade, endovascular revascularization has replaced surgical revascularization as the therapy of choice in most centers. This article reviews the most relevant clinical aspects of the disease and the current practice of diagnosis and treatment of CMI.
Career confidence and gendered expectations of academic promotion
Authors: Baker Maureen
Published: June 2010

This article discusses expectations of career progression, based on interviews with New Zealand-based university academics. In these interviews, most women said they did not expect to reach the professoriate before retirement while most men said they planned for and anticipated this promotion. The article attempts to explain gendered patterns of career confidence and progression by discussing academic practices and the backgrounds and experiences of academics, drawing on previous research on the ‘gender gap’ as well as interview findings. The article argues that perceptions and actual experiences of career support, collegiality and family circumstances are often gendered, influencing ambition and productivity. Integration into university networks and knowledge of work practices can be enhanced by mentoring programs but confidence and ambition are more difficult to influence because they are shaped by upbringing, professional experiences and family circumstances.
Psychosocial influences on children’s identification with sports teams
Authors: Spaaij Ramón , Anderson Alastair
Published: June 2010

The article examines the socialization of children into identification with a sports team. It presents a sociological approach which extends the insights obtained from research into psychological aspects of sports team identification. A conceptual model is presented which proffers an explanation of how and why children become supporters of a particular team. The model depicts the relationship between socializing agents, broader social influences and embodied dispositions. It is argued that these factors coalesce to influence children’s identification with a sports team. The article presents results of a qualitative study of young Australian Rules football supporters which show that their embryonic identification with a sports team is strongly influenced by parental and near family influences, particularly fathers and other male role models.
Structural health monitoring using video stream, influence lines, and statistical analysis
Authors: Zaurin Ricardo , Necati Catbas F.
Published: June 2010

Civil infrastructure systems experience damage, overloading, aging due to normal operations, severe environmental conditions, and extreme events. These effects change the structural behavior and performance. Novel structural health monitoring (SHM) strategies are increasingly becoming more important to objectively determine the actual condition and these changes. The main objective of this study is to demonstrate the integration of video images and sensor data as promising techniques for the safety of bridges in the context of SHM. The UCF 4-span bridge model is used to demonstrate the method. Image and sensing data are analyzed to obtain unit influence line (UIL) as an index for monitoring the bridge behavior under loading conditions identified using computer vision techniques. UILs are extracted for several different moving loads. In addition to the analysis of UILs in a comparative fashion, a new method based on statistical outlier detection from UIL vector sets is proposed and demonstrated. The new method is applied to detect and identify some of the most common damage scenarios for bridges such as changes in boundary conditions and loss of connectivity between composite sections. Successful results are obtained from the experimental studies.
Instantaneous phase and frequency for the detection of leaks and features in a pipeline system
Authors: Ghazali MF , Staszewski WJ , Shucksmith JD , Boxall JB , Beck SBM
Published: June 2010

This work focuses on the progress of a new analysis technique to detect pipeline leaks and features based on analysis of a pressure transient. The measured time domain signals of these transients were obtained using a single pressure transducer. The instantaneous phase and frequency of the signals are analyzed using the Hilbert transform (HT) and the Hilbert—Huang transform (HHT). Both simulated and experimental pressure signals were used to evaluate the performance of these transforms. The analysis of simulated signals allowed features in the pipeline network such as leaks and pipe ends to be ascribed to features in the signals. Analysis of the experimental tests corroborates the simulated test results when the HT and the HHT analysis are used.
Discussing Complementary Therapy Use With Early-Stage Breast Cancer Patients: Exploring the Communication Gap
Authors: Juraskova Ilona , Hegedus Leonard , Butow Phyllis , Smith Allan , Schofield Penelope
Published: June 2010

Objective. The current study aimed to (1) describe communication patterns between oncologists and breast cancer patients regarding the use of complementary and alternative medicine (CAM) and (2) assess the relationship between CAM discussions and anxiety levels. Methods. Interaction analysis of audiotaped initial consultations of 102 early-stage breast cancer patients with Australian and New Zealand oncologists was carried out. Preconsultation and postconsultation anxiety levels were assessed using the State-Trait Anxiety Inventory. Results. At least 1 instance of CAM discussion was found in 24 of the 102 consultations (24%). CAM discussions were mainly patient initiated (73%). The most common doctor’s response to a patient’s mention of CAM was encouragement (38%), although 23% of CAM references elicited a discouraging comment, and 20% were ignored. No patient demographics were significantly associated with CAM discussion. Patients who discussed CAM reported higher preconsultation and postconsultation anxiety levels than those who did not discuss CAM. Conclusions. CAM discussions during initial consultations between early-stage breast cancer patients and oncologists appear to be limited and linked with higher patient anxiety before and after the consultation. These findings indicate that doctors require further education about CAM therapies and supplements as well as guidance in how to raise and effectively discuss CAM issues with concern for their safety while balancing respect for the patients’ beliefs.
Review: Anti-adhesion molecule therapy for inflammatory bowel disease
Authors: Ghosh Subrata , Panaccione Remo
Published: June 2010

Although biologic agents directed against tumor necrosis factor alpha (TNFα) continue to be an effective therapeutic strategy for patients with inflammatory bowel disease (IBD), approximately 30% of patients with Crohn’s disease (CD) who are refractory to standard treatment do not respond to induction therapy with TNFα inhibitors and, of those who initially respond, 50% or more cease to respond within a year. Moreover, their use can be associated with significant safety issues. Clearly, there is a need to target alternative pathways involved in the inflammatory process. IBD is driven by the trafficking of lymphocytes from the circulation into the gut tissue that is mediated by adhesive interactions between the lymphocytes and endothelial cells. The adhesion molecules involved represent attractive targets for the development of new therapeutics which should aid in the resolution of existing inflammation, prevent recurrence of inflammation, and may potentially lead to long-term control of disease. In this article we review current opportunities and challenges facing anti-adhesion therapy in IBD, and discusses recent clinical development efforts that have focused on having an impact on two particular adhesive interactions: α4-integrin/MAdCAM-1 and β2-integrin/ICAM-1. Of particular interest is natalizumab, a humanized monoclonal antibody against human α4integrin that is approved for the treatment of patients with moderately-to-severely active CD and evidence of active inflammation. This agent represents an efficacious therapeutic option for patients who do not respond to, or have failed, a TNF-α inhibitor.
Current approach to the treatment of penile implant infections
Authors: Mulcahy John J.
Published: June 2010

Modern penile implants, introduced to the market almost four decades ago, have provided a predictable and reliable treatment of erectile dysfunction (ED) despite the development of less-invasive therapies. Infection associated with the placement of these devices does occur, and with prophylactic measures and protocols the incidence has decreased fortunately. In the presence of an infection the implant and all foreign material should be removed. A salvage procedure, during which the wound is thoroughly washed with antiseptic solutions after device removal and placement of a new implant during the same procedure, has a high success rate and is becoming a popular approach. The alternative, device removal with return at a later date for placing a new implant, entails a more difficult corporal dilation, and the resulting erection is noticeably shorter. Patient and partner satisfaction with a penile implant is the highest among all of the treatments for ED.
Health promotion through rediscovery of one’s sensibilities of health: the Lifemap and WIFY Methods
Authors: Moriyama Masaki
Published: June 2010

Japanese people place a high priority on maintaining social harmony and conforming with what we perceive to be mainstream thought and opinion. These social norms present challenges for developing health promotion policies and programs that value individual uniqueness and individual sensibilities about health. To address this challenge, over the past 20 years the author has developed two ‘write-and-share’ methods — Life-map and WIFY (What Is Important For you) to allow participants to reflect and rediscover their own and one another’s feelings about daily life and health. This article summarizes his experiences using these methods and discusses their possible usefulness in other Asian societies. (Global Health Promotion, 2010; 17(2): pp. 44—47)
Developing a national physical activity plan: the Kuwait example
Authors: Ramadan Jasem , Vuori Ilkka , Lankenau Becky , Schmid Tom , Pratt Michael
Published: June 2010

A rapid increase in economic well-being and urbanization in Kuwait have been accompanied by profound changes in lifestyle, including low levels of physical activity in all population groups. These changes have contributed to a high prevalence of overweight and obesity and to the escalation of the non-communicable disease rates, particularly coronary heart disease, stroke, hypertension and diabetes. The evolution of physical activity promotion, internationally, and a series of related meetings in Kuwait and neighboring countries, have started to generate an awareness among health authorities of the importance of physical activity in health promotion and disease prevention. A National Physical Activity Committee has been formed to design and implement a National Physical Activity Plan, which could also serve as a model for other countries. The authors describe the background and principles behind the development of the National Plan, summarize a template based upon the Kuwait experience and share the lessons learned from these efforts.
La Charte d’Ottawa rédigée en 2009? un 6ème axe en faveur de la recherche
Authors: Fortin Marilyn , Turcotte-Tremblay Anne-Marie , Ridde Valéry
Published: June 2010

Plus de deux décennies se sont écoulées depuis la rédaction de la Charte d’Ottawa. Des étudiants de l’Université de Montréal ont participé à un forum de discussion de l’Union Internationale de Promotion de la Santé et d’Éducation pour la Santé (UIPES) sur Views of Health Promotion Online (VHPO) pour échanger sur « Que serait le contenu de la Charte d’Ottawa si elle avait été rédigée en 2009 ? ». Les participants ont souligné la nécessité de promouvoir la Charte d’Ottawa, de renforcer son plaidoyer concernant les bénéfices de la promotion de la santé, d’aller au-delà des principes théoriques, de préconiser la synergie entre les axes, et d’encourager la recherche en promotion de la santé, notamment en y consacrant un sixième axe. Ces échanges ont permis de voir comment un groupe de la génération actuelle d’étudiants perçoit l’adaptation et la pertinence de la Charte d’Ottawa.
Rehausser le taux d’allaitement maternel exclusif dans la communauté urbaine de Niamey, au Niger : propositions des professionnels de la santé
Authors: Moussa Abba Aïssata , De Koninck Maria , Hamelin Anne-Marie
Published: June 2010

Les professionnels de la santé (PS) constituent la source la plus fiable d’informations en allaitement particulièrement pour une population majoritairement analphabète comme celle du Niger. Pour jouer efficacement ce rôle, ils ont besoin de disposer des connaissances et des compétences nécessaires en plus de bénéficier de conditions de travail leur permettant de développer des attitudes et d’adopter des pratiques conformes aux normes internationales. Dans le but de documenter les éventuelles améliorations à apporter en vue de contrer les obstacles à la promotion de l’allaitement maternel exclusif (AME) et rehausser le taux de pratique de l’AME, cette étude s’est intéressée, entre autres, à recueillir l’opinion des PS de la communauté urbaine de Niamey à travers des discussions de groupe organisées avec des infirmiers, des sages-femmes, des assistants sociaux et des médecins/pédiatres. Les participantes et participants ont suggéré différentes pistes de solutions susceptibles de favoriser les activités de promotion de l’AME au sein des formations sanitaires. Il s’agit d’interventions se situant au niveau structurel/organisationnel, programmatique et sur un plan plus individuel au niveau des pratiques et comportements des PS. Ces propositions pourraient être considérées par les responsables des établissements de santé en collaboration avec les décideurs, dans la planification, l’implantation et l’évaluation d’actions favorisant une promotion plus efficace de l’AME, notamment en ce qui concerne les attitudes et pratiques appropriées des intervenants centraux que sont les PS. (Global Health Promotion, 2010; 17 (2): pp. 62—71)
Enhanced c-Met activity promotes G-CSF–induced mobilization of hematopoietic progenitor cells via ROS signaling
Authors: Tesio Melania , Golan Karin , Corso Simona , Giordano Silvia , Schajnovitz Amir , Vagima Yaron , Shivtiel Shoham , Kalinkovich Alexander , Caione Luisa , Gammaitoni Loretta , Laurenti Elisa , Buss Eike C. , Shezen Elias , Itkin Tomer , Kollet Orit , Petit Isabelle , Trumpp Andreas , Christensen James , Aglietta Massimo , Piacibello Wanda , Lapidot Tsvee
Published: June 2010

Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor–induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell–derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1+/c-Kit+/Lin− cells and interfered with their enhanced chemotactic migration to stromal cell–derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met–mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.
Tropomodulin 1-null mice have a mild spherocytic elliptocytosis with appearance of Tropomodulin 3 in red blood cells and disruption of the membrane skeleton
Authors: Moyer Jeannette D. , Nowak Roberta B. , Kim Nancy E. , Larkin Sandra K. , Peters Luanne L. , Hartwig John , Kuypers Frans A. , Fowler Velia M.
Published: June 2010

The short actin filaments in the red blood cell (RBC) membrane skeleton are capped at their pointed ends by tropomodulin 1 (Tmod1) and coated with tropomyosin (TM) along their length. Tmod1-TM control of actin filament length is hypothesized to regulate spectrin-actin lattice organization and membrane stability. We used a Tmod1 knockout mouse to investigate the in vivo role of Tmod1 in the RBC membrane skeleton. Western blots of Tmod1-null RBCs confirm the absence of Tmod1 and show the presence of Tmod3, which is normally not present in RBCs. Tmod3 is present at only one-fifth levels of Tmod1 present on wild-type membranes, but levels of actin, TMs, adducins, and other membrane skeleton proteins remain unchanged. Electron microscopy shows that actin filament lengths are more variable with spectrin-actin lattices displaying abnormally large and more variable pore sizes. Tmod1-null mice display a mild anemia with features resembling hereditary spherocytic elliptocytosis, including decreased RBC mean corpuscular volume, cellular dehydration, increased osmotic fragility, reduced deformability, and heterogeneity in osmotic ektacytometry. Insufficient capping of actin filaments by Tmod3 may allow greater actin dynamics at pointed ends, resulting in filament length redistribution, leading to irregular and attenuated spectrin-actin lattice connectivity, and concomitant RBC membrane instability.
Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature
Authors: Kim Harold , Nguyen Vicky PKH , Petrova Tatiana V , Cruz Maribelle , Alitalo Kari , Dumont Daniel J
Published: June 2010

Background

In vivo studies demonstrate that the Prox1 transcription factor plays a critical role in the development of the early lymphatic system. Upon Prox1 expression, early lymphatic endothelial cells differentiate from the cardinal vein and begin to express lymphatic markers such as VEGFR-3, LYVE-1 and Podoplanin. Subsequent in vitro studies have found that differentiated vascular endothelial cells can be reprogrammed by Prox1 to express a lymphatic gene profile, suggesting that Prox1 can initiate the expression of a unique gene signature during lymphangiogenesis. While the in vitro data suggest that gene reprogramming occurs upon Prox1 expression, it is not clear if this is a direct result of Prox1 in vascular endothelial cells in vivo.

Results

Overexpression of Prox1 in vascular endothelial cells during embryonic development results in the reprogramming of genes to that of a more lymphatic signature. Consequent to this overexpression, embryos suffer from gross edema that results in embryonic lethality at E13.5. Furthermore, hemorrhaging and anemia is apparent along with clear defects in lymph sac development. Alterations in junctional proteins resulting in an increase in vascular permeability upon Prox1 overexpression may contribute to the complications found during embryonic development.

Conclusion

We present a novel mouse model that addresses the importance of Prox1 in early embryonic lymphangiogenesis. It is clear that there needs to be a measured pattern of expression of Prox1 during embryonic development. Furthermore, Prox1 reprograms vascular endothelial cells in vivo by creating a molecular signature to that of a lymphatic endothelial cell.
Microarray analysis of a salamander hopeful monster reveals transcriptional signatures of paedomorphic brain development
Authors: Page Robert B , Boley Meredith A , Smith Jeramiah J , Putta Srikrishna , Voss Stephen R
Published: June 2010

Background

The Mexican axolotl (Ambystoma mexicanum) is considered a hopeful monster because it exhibits an adaptive and derived mode of development - paedomorphosis - that has evolved rapidly and independently among tiger salamanders. Unlike related tiger salamanders that undergo metamorphosis, axolotls retain larval morphological traits into adulthood and thus present an adult body plan that differs dramatically from the ancestral (metamorphic) form. The basis of paedomorphic development was investigated by comparing temporal patterns of gene transcription between axolotl and tiger salamander larvae (Ambystoma tigrinum tigrinum) that typically undergo a metamorphosis.

Results

Transcript abundances from whole brain and pituitary were estimated via microarray analysis on four different days post hatching (42, 56, 70, 84 dph) and regression modeling was used to independently identify genes that were differentially expressed as a function of time in both species. Collectively, more differentially expressed genes (DEGs) were identified as unique to the axolotl (n= 76) and tiger salamander (n= 292) than were identified as shared (n= 108). All but two of the shared DEGs exhibited the same temporal pattern of expression and the unique genes tended to show greater changes later in the larval period when tiger salamander larvae were undergoing anatomical metamorphosis. A second, complementary analysis that directly compared the expression of 1320 genes between the species identified 409 genes that differed as a function of species or the interaction between time and species. Of these 409 DEGs, 84% exhibited higher abundances in tiger salamander larvae at all sampling times.

Conclusions

Many of the unique tiger salamander transcriptional responses are probably associated with metamorphic biological processes. However, the axolotl also showed unique patterns of transcription early in development. In particular, the axolotl showed a genome-wide reduction in mRNA abundance across loci, including genes that regulate hypothalamic-pituitary activities. This suggests that an axolotls failure to undergo anatomical metamorphosis late in the larval period is indirectly associated with a mechanism(s) that acts earlier in development to broadly program transcription. The axolotl hopeful monster provides a model to identify mechanisms of early brain development that proximally and ultimately affect the expression of adult phenotypes.
Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas
Authors: De Chiara Loretta , Rodríguez-Piñeiro Ana M , Rodríguez-Berrocal Francisco J , Cordero Oscar J , Martínez-Ares David , Páez de la Cadena María
Published: June 2010

Background

Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed.

Methods

sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC.

Results

At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%).

Conclusions

Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary.
Elevated MED28 expression predicts poor outcome in women with breast cancer
Authors: Yoon Nam K , Maresh Erin L , Elshimali Yahya , Li Ai , Horvath Steve , Seligson David B , Chia David , Goodglick Lee
Published: June 2010

Background

MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in
vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression.

Methods

Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed.

Results

MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death.

Conclusions

We have demonstrated that MED28 expression is increased in breast cancer. In addition, although the patient size was limited (88 individuals with survival information) MED28 is a novel and strong independent prognostic indicator of survival for breast cancer.
An 8-gene qRT-PCR-based gene expression score that has prognostic value in early breast cancer
Authors: Sánchez-Navarro Iker , Gámez-Pozo Angelo , Pinto Álvaro , Hardisson David , Madero Rosario , López Rocío , San José Belén , Zamora Pilar , Redondo Andrés , Feliu Jaime , Cejas Paloma , González Barón Manuel , Ángel Fresno Vara Juan , Espinosa Enrique
Published: June 2010

Background

Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.

Methods

We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.

Results

An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.

Conclusions

This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.
Identifying structures, processes, resources and needs of research ethics committees in Egypt
Authors: Sleem Hany , El-Kamary Samer S , Silverman Henry J
Published: June 2010

Background

Concerns have been expressed regarding the adequacy of ethics review systems in developing countries. Limited data are available regarding the structural and functional status of Research Ethics Committees (RECs) in the Middle East. The purpose of this study was to survey the existing RECs in Egypt to better understand their functioning status, perceived resource needs, and challenges.

Methods

We distributed a self-administered survey tool to Egyptian RECs to collect information on the following domains: general characteristics of the REC, membership composition, ethics training, workload, process of ethics review, perceived challenges to effective functioning, and financial and material resources. We used basic descriptive statistics to evaluate the quantitative data.

Results

We obtained responses from 67% (12/18) of the identified RECs. Most RECs (10/12) have standard operating procedures and many (7/12) have established policies to manage conflicts of interests. The average membership was 10.3 with a range from 7-19. The predominant member type was physicians (69.5% of all of the REC members) with little lay representation (13.7%). Most RECs met at least once/month and the average number of protocols reviewed per meeting was 3.8 with a range from 1-10. Almost three-quarters of the members from all of the 12 RECs indicated they received some formal training in ethics. Regarding resources, roughly half of the RECs have dedicated capital equipment (e.g., meeting room, computers, office furniture, etc); none of the RECs have a formal operating budget. Perceived challenges included the absence of national research ethics guidelines and national standards for RECs and lack of ongoing training of its members in research ethics.

Conclusion

Our study documents several areas of strengths and areas for improvements in the operations of Egyptian RECs. Regarding strengths, many of the existing RECs meet frequently, have a majority of members with prior training in research ethics, and have written policies. Regarding areas for improvements, many RECs should strive for a more diverse membership and should receive more financial resources and administrative support personnel. We recommend that RECs include more individuals from the community and develop a continuing educational program for its members. Institutional officials should be aware of the resource capacity needs of their RECs.
Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats
Authors: Leu Steve , Lin Yu-Chun , Yuen Chun-Man , Yen Chia-Hung , Kao Ying-Hsien , Sun Cheuk-Kwan , Yip Hon-Kan
Published: June 2010

Background

The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.

Methods

Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 × 106) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.

Results

The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).

Conclusions

ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.
Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans
Authors: Brys Kristel , Castelein Natascha , Matthijssens Filip , Vanfleteren Jacques R , Braeckman Bart P
Published: June 2010

Background

The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan.

Results

We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370) adult animals. The increase in daf-2(e1370) mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370) animals.

Conclusions

We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.
Hypolocomotion, Asymmetrically Directed Behaviors (Licking, Lifting, Flinching, and Shaking) and Dynamic Weight Bearing (Gait) Changes are Not Measures of Neuropathic Pain in Mice
Authors: Mogil Jeffrey S , Graham Allyson C , Ritchie Jennifer , Hughes Sara F , Austin Jean-Sebastien , Schorscher-Petcu Ara , Langford Dale J , Bennett Gary J
Published: June 2010

Background:

Spontaneous (non-evoked) pain is a major clinical symptom of neuropathic syndromes, one that is understudied in basic pain research for practical reasons and because of a lack of consensus over precisely which behaviors reflect spontaneous pain in laboratory animals. It is commonly asserted that rodents experiencing pain in a hind limb exhibit hypolocomotion and decreased rearing, engage in both reflexive and organized limb directed behaviors, and avoid supporting their body weight on the affected side. Furthermore, it is assumed that the extent of these positive or negative behaviors can be used as a dependent measure of spontaneous chronic pain severity in such animals. In the present study, we tested these assumptions via blinded, systematic observation of digital video of mice with nerve injuries (chronic constriction or spared nerve injury), and automated assessment of locomotor behavior using photocell detection and dynamic weight bearing (i.e., gait) using the CatWalk® system.

Results:

We found no deficits in locomotor activity or rearing associated with neuropathic injury. The frequency of asymmetric (ipsilaterally directed) behaviors were too rare to be seriously considered as representing spontaneous pain, and in any case did not statistically exceed what was blindly observed on the contralateral hind paw and in control (sham operated and unoperated) mice. Changes in dynamic weight bearing, on the other hand, were robust and ipsilateral after spared nerve injury (but not chronic constriction injury). However, we observed timing, pharmacological, and genetic dissociation of mechanical allodynia and gait alterations.

Conclusions:

We conclude that spontaneous neuropathic pain in mice cannot be assessed using any of these measures, and thus caution is warranted in making such assertions.
microRNA evolution in a human transcription factor and microRNA regulatory network
Authors: Qiu Chengxiang , Wang Juan , Yao Pengying , Wang Edwin , Cui Qinghua
Published: June 2010

Background

microRNAs (miRNAs) are important cellular components. The understanding of their evolution is of critical importance for the understanding of their function. Although some specific evolutionary rules of miRNAs have been revealed, the rules of miRNA evolution in cellular networks remain largely unexplored. According to knowledge from protein-coding genes, the investigations of gene evolution in the context of biological networks often generate valuable observations that cannot be obtained by traditional approaches.

Results

Here, we conducted the first systems-level analysis of miRNA evolution in a human transcription factor (TF)-miRNA regulatory network that describes the regulatory relations among TFs, miRNAs, and target genes. We found that the architectural structure of the network provides constraints and functional innovations for miRNA evolution and that miRNAs showed different and even opposite evolutionary patterns from TFs and other protein-coding genes. For example, miRNAs preferentially coevolved with their activators but not with their inhibitors. During transcription, rapidly evolving TFs frequently activated but rarely repressed miRNAs. In addition, conserved miRNAs tended to regulate rapidly evolving targets, and upstream miRNAs evolved more rapidly than downstream miRNAs.

Conclusions

In this study, we performed the first systems level analysis of miRNA evolution. The findings suggest that miRNAs have a unique evolution process and thus may have unique functions and roles in various biological processes and diseases. Additionally, the network presented here is the first TF-miRNA regulatory network, which will be a valuable platform of systems biology.
Early fluid resuscitation with hyperoncotic hydroxyethyl starch 200/0.5 (10%) in severe burn injury
Authors: Béchir Markus , Puhan Milo A , Neff Simona B , Guggenheim Merlin , Wedler Volker , Stover John F , Stocker Reto , Neff Thomas A
Published: June 2010

Introduction

Despite large experience in the management of severe burn injury, there are still controversies regarding the best type of fluid resuscitation, especially during the first 24 hours after the trauma. Therefore, our study addressed the question whether hyperoncotic hydroxyethyl starch (HES) 200/0.5 (10%) administered in combination with crystalloids within the first 24 hours after injury is as effective as 'crystalloids only' in severe burn injury patients.

Methods

30 consecutive patients were enrolled to this prospective interventional open label study and assigned either to a traditional 'crystalloids only' or to a 'HES 200/0.5 (10%)' volume resuscitation protocol. Total amount of fluid administration, complications such as pulmonary failure, abdominal compartment syndrome, sepsis, renal failure and overall mortality were assessed. Cox proportional hazard regression analysis was performed for binary outcomes and adjustment for potential confounders was done in the multivariate regression models. For continuous outcome parameters multiple linear regression analysis was used.

Results

Group differences between patients receiving crystalloids only or HES 200/0.5 (10%) were not statistically significant. However, a large effect towards increased overall mortality (adjusted hazard ratio 7.12; P = 0.16) in the HES 200/0.5 (10%) group as compared to the crystalloids only group (43.8% versus 14.3%) was present. Similarly, the incidence of renal failure was 25.0% in the HES 200/0.5 (10%) group versus 7.1% in the crystalloid only group (adjusted hazard ratio 6.16; P = 0.42).

Conclusions

This small study indicates that the application of hyperoncotic HES 200/0.5 (10%) within the first 24 hours after severe burn injury may be associated with fatal outcome and should therefore be used with caution.

Trial registration

NCT01120730.
Early Discontinuation and Nonadherence to Adjuvant Hormonal Therapy in a Cohort of 8,769 Early-Stage Breast Cancer Patients
Authors: Hershman Dawn L. , Kushi Lawrence H. , Shao Theresa , Buono Donna , Kershenbaum Aaron , Tsai Wei-Yann , Fehrenbacher Louis , Lin Gomez Scarlett , Miles Sunita , Neugut Alfred I.
Published: June 2010

Purpose

While studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system.

Patients and Methods

We identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio < 80%) of hormonal therapy.

Results

We identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent.

Conclusion

Only 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.
Meta-Analysis on the Use of Zidovudine and Interferon-Alfa in Adult T-Cell Leukemia/Lymphoma Showing Improved Survival in the Leukemic Subtypes
Authors: Bazarbachi Ali , Plumelle Yves , Carlos Ramos Juan , Tortevoye Patricia , Otrock Zaher , Taylor Graham , Gessain Antoine , Harrington William , Panelatti Gérard , Hermine Olivier
Published: June 2010

Purpose

Human T-cell lymphotropic virus type-I–associated adult T-cell leukemia/lymphoma (ATL) is an aggressive, chemotherapy-resistant malignancy. Multiple small studies using zidovudine (AZT) and interferon-alfa (IFN-α) have shown response in patients with ATL. However, the impact of this innovative antiviral treatment strategy on long-term survival remains undetermined.

Patients and Methods

We report a meta-analysis of antiviral therapy of ATL. Medical records of 254 patients with ATL who were treated in the United States, the United Kingdom, Martinique, and continental France were individually reviewed.

Results

According to Shimoyama classification, there were 116 patients with acute ATL, 18 patients with chronic ATL, 11 patients with smoldering ATL, and 100 patients with ATL lymphoma. In 231 patients with available survival data, first-line therapy was recorded in 207 patients. Five-year overall survival rates were 46% for 75 patients who received first-line antiviral therapy (P = .004), 20% for 77 patients who received first-line chemotherapy, and 12% for 55 patients who received first-line chemotherapy followed by antiviral therapy. Patients with acute, chronic, and smoldering ATL significantly benefited from first-line antiviral therapy, whereas patients with ATL lymphoma experienced a better outcome with chemotherapy. In acute ATL, achievement of complete remission with antiviral therapy resulted in 82% 5-year survival. Antiviral therapy in chronic and smoldering ATL resulted in 100% 5-year survival. Multivariate analysis confirmed that first-line antiviral therapy significantly improves overall survival of patients with ATL (hazard ratio, 0.47; 95% CI, 0.27 to 0.83; P = .021).

Conclusion

These results confirm the high efficacy of AZT and IFN, which should now be considered the gold standard first-line therapy in leukemic subtypes of ATL.