bluuebunny/crossref_metadata_2025 huggingface dataset:
The modulatory effects of garlic oil on hepatic cytochrome P450s in mice
Authors: Zeng Tao , Zhang Cui-Li , Song Fu-Yong , Han Xiao-Ying , Xie Ke-Qin
Published: October 2009

In order to probe into the effects of garlic oil (GO) on the hepatic CYP2E1, CYP1A2 and CYP3A, male Kun-Ming mice were treated with GO (100 mg/kg body weight) or corn oil for 1 day or consecutive 60 days, respectively, and then the protein expressions and the activities of the enzymes were examined. GO did not alter the physical activities of mice and did not induce lesion to the liver. However, it dramatically inhibited the activities and protein levels of hepatic CYP2E1 and 1A2, but not CYP3A. In addition, we noticed that the inhibition of CYP2E1 and 1A2 by GO was more potent in group of 1 day treatment than those in group of 60 days treatment. Compared with the respective control value, the protein levels of CYP2E1 were decreased by 87.40% (p < .01) and 62.26% (p < .01) by 1 day and 60 days of GO treatment, respectively, while the CYP1A2 protein levels were decreased by 70.76% (p < .01) and 41.49% (p < .01), respectively. These data indicated that the mice could adapt to the prolonged treatment, which might be one reasonable explanation for the conflicting data in the literature. The CYP2E1 and 1A2 suppression might contribute to its hepatoprotection, and data about CYP3A indicated that GO was unlikely to alter the metabolism of the concomitantly used drugs.
Antibodies to DNA: infection or genetics?
Authors: Pisetsky DS , Vrabie IA
Published: October 2009

Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus (SLE) and unique markers of the immunological disturbances critical to disease pathogenesis. In the form of immune complexes, anti-DNA autoantibodies can deposit in the tissue to incite inflammation and damage; in addition, these complexes can induce cytokine production, most prominently, type 1 interferon. Studies in both patients and animal models have implicated genetic as well as environmental factors in the aetiology of the anti-DNA response. Because bacterial DNA is a potent stimulant of innate immunity by both toll-like receptor (TLR) and non-TLR signalling pathways, foreign DNA introduced during the course of bacterial or viral infection could have a dual role in antibody induction. This DNA could serve as an adjuvant to activate innate immunity as well as an immunogen to drive an antigen-specific antibody response. In this scenario, the generation of cross-reactive autoantibodies, in contrast to highly specific antibodies to bacterial DNA, most likely depends on genetically determined abnormalities in the B-cell repertoire in patients with SLE. Given the universal expression of DNA, this model suggests that many different kinds of infections could trigger pathogenic autoantibody responses in SLE, as well as induce flare.
Regulation of cellular immunity prevents Helicobacter pylori-induced atherosclerosis
Authors: Ayada K. , Yokota K. , Hirai K. , Fujimoto K. , Kobayashi K. , Ogawa H. , Hatanaka K. , Hirohata S. , Yoshino T. , Shoenfeld Y. , Matsuura E. , Oguma K.
Published: October 2009

Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe+/ −-ldlr+/−-mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis. Lupus (2009) 18, 1154—1168.
Infection—genetics relationship in systemic lupus erythematosus
Authors: Sebastiani G. Domenico , Galeazzi M.
Published: October 2009

Genetic, environmental, and hormonal factors contribute to disease susceptibility in systemic lupus erythematosus. Among environmental factors, infectious agents play a major role. When considering the complex relationship between genetic predisposition and infections in the pathogenesis of systemic lupus erythematosus, we have to consider that infectious agents can interact with the immune system in several ways. For example, molecular mimicry, altered apoptosis of the host cells, exposure of as yet masked antigens to the immune system by a given microorganism, and direct viral invasion of immunocompetent cells are all mechanisms that may give rise to dysfunction of the immune system; in addition, some genetically determined deficit of the immune system, such as complement deficiency or deficit of mannose binding lectine, may cause insufficient clearance of infectious agents, whose persistence in the host may determine autoimmunity. Finally, evidence has been emerging suggesting that the production of autoantibodies, by infected B-lymphocytes, may be drawn by altered expression of particular microRNA in these cells. In this paper, we review some of the distinct scenarios that can account for the role of infectious agents, acting on a genetically prone host, in determining systemic lupus erythematosus.
Safety of vaccination of patients with systemic lupus erythematosus
Authors: Abu-Shakra M.
Published: October 2009

Live vaccines are not safe for immuno-compromised patients and should not be given to patients with systemic lupus erythematosus. In addition, all vaccines are not recommended for systemic lupus erythematosus patients when their disease is very active and mainly for patients with very active lupus nephritis. Systemic lupus erythematosus patients with quiescent or mildly active disease should be encouraged to receive vaccination according the recommendations given by the Immunization Practices Advisory Committee. Among this group of systemic lupus erythematosus patients, vaccines are safe and they do not affect the clinical manifestations of systemic lupus erythematosus including renal features, disease activity, or the requirement for steroids or cytotoxic drugs. However, vaccines may trigger the generation of autoantibodies which is usually short term and has no clinical significance. In individual cases vaccines exacerbate systemic lupus erythematosus; however, no specific clinical or laboratory variables have been identified to be associated with flare of systemic lupus erythematosus following vaccination. Lupus (2009) 18, 1205—1208.
Gender Differences in Behavioral Outcomes Among Children at Risk of Neglect: Findings From a Family-Focused Prevention Intervention
Authors: Lindsey Michael A. , Hayward R. Anna , DePanfilis Diane
Published: October 2009

Objective: This study examines the impact of the Family Connections (FC) intervention on preventing behavioral problems among urban, predominantly African American children at risk of neglect. Method: Secondary data analyses using mixed model analyses of variance (ANOVA) with repeated measures were used to examine gender differences in child behavior outcomes among 111 participating families across three time points (intake, closing, and 6 months following intervention participation). Results: From intake to closing, boys appeared to experience a larger decrease in internalizing and externalizing behaviors than girls. At 6-month follow-up, boys’ behaviors remained stable relative to results at closing; girls showed a slight decrease in behaviors over the same period. Findings also indicate a greater decrease in problem behaviors for participants in the 9-month versus 3-month version of FC. Conclusions: Positive effects of the FC intervention for African American children indicate the potential of this prevention intervention to avert negative behavior trajectories.
Metanephric Stromal Tumor Arising in a Patient With Neurofibromatosis Type 1 Syndrome
Authors: McDonald Oliver G. , Rodriguez Ron , Bergner Amanda , Argani Pedram
Published: October 2009

Metanephric stromal tumor (MST) is a recently recognized benign renal stromal tumor. MST is thought to be part of a spectrum of benign metanephric renal lesions, which also includes the epithelial lesion metanephric adenoma and the mixed stromal–epithelial lesion metanephric adenofibroma. Metanephric lesions may represent hyperdifferentiated counterparts to Wilms’ tumor (WT). MST characteristically shows renovascular angiodysplasia and juxtaglomerular (JG) cell hyperplasia. This is remarkably similar to the renal pathology described in neurofibromatosis-1 (NF-1) syndrome, a condition which is also associated with WT. Here, we report the first case of MST arising in a patient with NF-1. The patient presented with hypertension, and the MST was associated with florid angiodysplasia and JG cell hyperplasia. This case tightens the link between NF-1, WT, and MST.
The Impact of Nonphysician Clinicians
Authors: Laurant Miranda , Harmsen Mirjam , Wollersheim Hub , Grol Richard , Faber Marjan , Sibbald Bonnie
Published: October 2009

Health care is changing rapidly. Unacceptable variations in service access and quality of health care and pressures to contain costs have led to the redefinition of professional roles. The roles of nonphysician clinicians (nurses, physician assistants, and pharmacists) have been extended to the medical domain. It is expected that such revision of roles will improve health care effectiveness and efficiency. The evidence suggests that nonphysician clinicians working as substitutes or supplements for physicians in defined areas of care can maintain and often improve the quality of care and outcomes for patients. The effect on health care costs is mixed, with savings dependent on the context of care and specific nature of role revision. The evidence base underpinning these conclusions is strongest for nurses with a marked paucity of research into pharmacists and physician assistants. More robust evaluative studies into role revision are needed, particularly with regard to economic impacts, before definitive conclusions can be drawn.
Young people and social capital
Authors: Holland Janet
Published: October 2009

The concept of social capital has gained wide currency in recent years in sociology and related areas, including youth studies. Politicians and policy makers have eagerly taken it up, seeing building and enhancing social capital as a solution for difficult policy issues, and it has been at the core of Third Way politics. This article provides a general review of social capital, critically examining issues raised by the academic and political use of the concept related to its journey through several academic disciplines, and to its perceived value as a guide to policy. Selected examples of its use in studying the lives and experiences of young people are discussed, as is the extensive research undertaken by myself and colleagues in a five-year multi-project study of families and social capital, focusing on our work on young people.
Insecurity of young people
Authors: Vornanen Riitta , Törrönen Maritta , Niemelä Pauli
Published: October 2009

This article critically examines the concept of insecurity as experienced by young people in Finland. Young people’s own definitions of insecurity show how 13–17-year-olds assess their lives and ontological insecurities and threats in the world. The topic is analyzed from a social sciences perspective and interpreted within the theoretical framework of risk society by Ulrich Beck (1996; 2001), Anthony Giddens (1991) and Franz-Xavier Kaufmann (1970).

The data was collected from schools in five regions in Finland. A total of 922 respondents aged 13 to 17 completed a questionnaire in classroom settings. This article analyzes only the data elicited by open-ended questions, which were answered by 683 young people.

Young people’s experiences of insecurity were classified into 16 categories, which were then divided under three headings: (i) the inner circle, that is, insecurity related to personal emotions and inner experiences; (ii) the social circle, that is, insecurity related to social interaction; and (iii) the outer circle, that is, insecurity related to external realities. Young people’s definitions of insecurity reveal their perspective on risk society in which everyone is vulnerable to certain risks.The answers disclose a set of contradictory risks, which are at the same time personal, local and global. First, they connect insecurity to their inner feelings and emotions. Second, they interpret the social relationships and the everyday life experiences in connection with insecurity. Third, insecurity is defined by young people by external realities, such as socio-economic ill-being, violence and war.

In the future, more empirical and qualitative research on risk society and how it is experienced by young people in the everyday life is needed. How do young people connect close and distant security issues and insecurity to their everyday life?
Global citizenship and the ‘New, New’ social movements
Authors: Feixa Carles , Pereira Inês , Juris Jeffrey S.
Published: October 2009

The past two decades have witnessed the rise of a new global cycle of collective action not only organized through the Internet and made visible during mass pro-test events, but also locally shaped by diverse organizations, networks, platforms and groups. Focusing on specific cases in two Iberian cities — Barcelona and Lisbon — we argue that this protest cycle has given rise to new kinds of movements referred to here as ‘new, new’ social movements. We analyze particular aspects of each case, but also discuss their European and global dimensions. The article will also highlight the role of youth, discussing the characteristics associated with the participation of young people in the ‘new, new’ movements. After a short introduction to the research on this topic, focusing on the emergence of the ‘anti-corporate globalization movement’ and related theoretical implications, we provide a description of four protest events in Barcelona and Lisbon. Next, we analyze the local contexts that anchor these events. Finally, we discuss the main characteristics of the ‘new, new’ social movements, examining the links between Barcelona and Lisbon and the wider international context that shapes them and paying particular attention to contemporary networking dynamics.
Working Notions of Active Audiences
Authors: Sundet Vilde Schanke , Ytreberg Espen
Published: October 2009

Recent research on the media industries has been centrally concerned with the blurring of boundaries between production and reception in an era of digitalization and convergence. The article argues for a need for research to consider more closely the importance of notions of the ‘active audience’ within today’s media industries. Overall conceptual work has been done on ‘convergence culture’, and much scholarly debate currently centres around the pros and cons of convergence; whether it empowers ‘produsers’ or the industries themselves. Important as they are, these debates run the risk of stagnation if they are not informed by further empirical research on the concrete ways that media institutions put ‘activity’ to strategic use. The article reports from a survey on how notions of activity, sociability and technological novelty function as strategic ‘working notions’ for Norwegian media industry executives.
New Media for New Organs
Authors: Bers Marina U.
Published: October 2009

This article describes an eight-month pilot study in which 19 pediatric post-transplant patients at Children’s Hospital Boston, ages 11 to 15, used a computer-based psychosocial intervention developed on the Zora 3D multiuser environment. Zora provides tools to create an online virtual city and populate it with houses and personally-meaningful objects. Users can communicate with each other via real-time chat and participate in open-ended guided activities to create a social network of peers. Preliminary results support the idea that innovative technologies can help adolescent patients to create a support network of peers when face-to-face interactions are impossible.
Media Crisis Management in Traditional and Digital Newsrooms
Authors: Olsson Eva-Karin
Published: October 2009

By comparing two newsrooms’ responses, one with a traditional mode of production and one with a digital, to the terror attacks of 9/11, this article demonstrates that newsrooms, in contrast to what previous research tells us, differ in their ability to cover crisis events. Drawing upon findings from previous research on how news organizations cope with extraordinary — and crisis — events, the study explains news desks’ ability to cope with the disruptions of everyday deadlines caused by ‘disaster marathon modes’ of reporting, based on organizational everyday structures and previous experiences. The study concludes that a digital newsroom designed to handle 24 hour reporting does not necessarily nor automatically have a suitable structure to deal with a crisis event. Rather, in this particular case the structure used for 24/7 coverage, based on journalists’ independence and decentralization, was directly counterproductive when dealing with a crisis event.
Radical pluralism and free speech in online public spaces
Authors: Cammaerts Bart
Published: October 2009

• Progressive political movements and activists are not the only ones appropriating Web 2.0 as a way to construct independent public spaces and voice counter-hegemonic discourses. By studying (post-) fascist movements, it will be shown that the internet also gives rise to anti-public spaces, voicing hatred and essentialist discourses. In this article, discourses of hate produced by North Belgian (post-)fascist movements and activists will be analysed. Theoretically the analysis is informed by radical pluralism and the limits of freedom of speech in a strong democracy. The cases presented challenge the limits of freedom of speech and of radical pluralism, and bring us to question whether being a racist is a democratic right, whether freedom of speech includes opinions and views that challenge basic democratic values. •
Too cool for school?
Authors: Winstanley Carrie
Published: October 2009

Homeschooling can be a last resort for frustrated families where gifted children are not having their complex needs met through mainstream schooling. Unlike many other groups of homeschoolers, parents of highly able children take this option for pragmatic reasons rather than as a kind of moral stance. This article explores some of the ways that standard schools fail gifted children and presents the perspectives of families who have made the choice to remove their gifted children from the mainstream education system. The difficulties inherent in researching both homeschooling and gifted education are also highlighted.
Homeschooling in the USA
Authors: Gaither Milton
Published: October 2009

This article first examines why the homeschooling movement in the USA emerged in the 1970s, noting the impact of political radicalism both right and left, feminism, suburbanization, and public school bureaucratization and secularization. It then describes how the movement, constituted of left- and right-wing elements, collaborated in the early 1980s to contest hostile legal climates in many states but was taken over by conservative Protestants by the late 1980s because of their superior organization and numerical dominance. Despite internal conflicts, the movement’s goals of legalizing and popularizing homeschooling were realized by the mid-1990s. Since that time homeschooling has grown in popularity and is increasingly being utilized by more mainstream elements of society, often in conjunction with public schools, suggesting that ‘homeschooling’ as a political movement and ideology may have run its course.
Poverty Pimps in the Academy: A Dialogue About Subjectivity, Reflexivity, and Power in Decolonizing Production of Knowledge
Authors: Diversi Marcelo , Finley Susan
Published: October 2009

The authors often talk about the moral and ethical predicaments they experience working with marginalized populations. But such conversations, confessions, and verbalized doubts happened in intimate settings, often with out office doors closed or when the hallways are quiet and empty. This is not a whisper of secrecy or conspiracy but one of self-reflexive contemplation about the privilege differential between the authors and the humans they encounter in the streets as they conduct action research or simple walk around as citizen observers. Through this dialogue, the authors attempt to capture some of the conversations they have had about the unspoken internal conflict faced by the scholars, including the authors, doing forms of action research with fellow humans who continue to suffer under the self-righteous ideologies of justified domination. The central force behind this dialogical article is not to offer solutions but to problematize the lack of narrative space and language for the colonialist reenactments every poverty scholar have to live with, even as they aim at decolonizing and empowering scholarship. The authors hope this dialogue is evocative enough to invite others to further explore similar dilemmas of decolonizing scholarship.
Making a Living: The Gringo Ethnographer as Pimp of the Suffering in the Late Capitalist Night
Authors: Veissiere Samuel P. L.
Published: October 2009

Set in the criminalized, racialized, and sexualized streets of Salvador da Bahia, this article presents experimental ethnographic glimpses of the deeply transnational aspects of desire, suffering, and violence in the disintegrating public spaces of a Northeastern Brazilian city famous for its global tourism fuelled by transnational desire for and consumption of Afro-Brazilian culture and bodies. The author reflects on the possibility of critical engagement between academic ethnographers from the North and the sex workers, street kids, crack users, and other marginalized social actors who make a living in the street. Refraining from facile, depoliticized celebrations of grassroots “critical” anthropology and other fantasies about empowering the subaltern, the author depicts the terror-as-usual at Bahian-street livelihoods from the necessarily exploitative position of a gringo ethnographer who is also making a living and a career from writing about the suffering of others. While this article, like all of Veissière’s work, is ultimately committed to a search for postcolonial social justice and critical dialogues between intellectuals and the subaltern, it also contemplates the horror of being an academic pimp who sustains a livelihood from exploiting human suffering and violence.
Issues of Power in Collaborative Research With Dignity Village
Authors: Mosher Heather I.
Published: October 2009

In this article, the author will utilize her fieldnotes and videotaped interviews to reconstruct and reflect on her experiences and some of the ethical dilemmas she faced as a community partner in participatory action research with a self-governed homeless encampment called Dignity Village. The author’s yearlong facilitation utilized a democratic, collaborative, and inclusive process. Following the final stages of the research, an abrupt shift of power occurred in the community. She explores questions about her involvement in this power shift and whether the change was problematic or healthy for the community.
This Is home, or Is It?: Disrupting Grand Narratives of Home as Physical or Institutional Space
Authors: Moreira Claudio
Published: October 2009

In this article, as suggest by the subtitle, I try to expose a kind of hidden homelessness. One that is not worse than others but important to bring to light. One where narratives are missing. One that goes against the essentializing of home as a middle-class heterosexual construction while not negating the desire for a home by the ones that have none.This is a textual performance about the idea of linking traditional notions of home with how academic knowledge is constructed about the homeless—by disrupting grand narratives of home as physical or institutional space. It is a decolonizing performance autoethnography exposing homelessness that returns its gaze into the process of knowledge production in the hope that by reflecting on how knowledge is produced, troubling the Western concept of home, we academics may create narratives that help more people feel housed.
The moral construction of the good pupil embedded in school rules
Authors: Thornberg Robert
Published: October 2009

The aim of this field study was to investigate the hidden curriculum of school rules delimited to the moral construction of ‘the good pupil’ embedded in the system of school rules in two primary schools. According to the findings, the rule system mediates a moral construction of the good pupil to the children, and this actually includes two constructions: the benevolent fellow buddy and the well-behaved pupil. Furthermore, a picture of a final learning outcome of this hidden or implicit citizenship education of school rules emerges: the good citizen who (1) does good to others and does not harm others, (2) functions well in the society and lives by its laws and norms, and (3) takes responsibility and does her or his very best. Critical thinking and the possibility of questioning, critically discussing and abolishing explicit rules are not parts of this picture.
The effect of the tachykinin NK2 receptor antagonist MEN11420 (nepadutant) on neurokinin A-induced bronchoconstriction in asthmatics
Authors: Schelfhout Venessa , Van De Velde Veerle , Maggi Carlo , Pauwels Romain , Joos Guy
Published: October 2009

Objective: We previously reported that the nonpeptide tachykinin NK2 receptor antagonist SR48968 (saredutant) significantly inhibits neurokinin A-induced bronchoconstriction in patients with asthma. MEN11420 (nepadutant) is a bicyclic peptide tachykinin NK2 receptor antagonist. The aim of the trial was to examine the effect of nepadutant on neurokinin A-induced bronchoconstriction in man.

Methods: 12 patients with stable, mild to moderate asthma participated in a double-blind, placebo-controlled crossover trial and received, with intervals of 1 week, MEN11420 2 mg, MEN11420 8 mg and placebo (i.v.). Increasing concentrations of NKA (10-9 to 10-6 moles/ml) were inhaled immediately after (d1) and 24 hours after (d2) administration of treatment.

Results: On d1 both MEN11420 2 and 8 mg shifted the dose response curve for neurokinin A to the right (log PC20 FEV1 neurokinin A [moles/ml]; mean± SEM -6.38±0.26 after 2 mg, -6.11±0.23 after 8 mg, versus -6.95±0.27 after placebo]. On d2 MEN11420 had no effect on neurokinin A-induced bronchoconstriction.

Conclusion: In conclusion, the tachykinin NK2 receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma.
A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma
Authors: Lokhorst Henk M. , van der Holt Bronno , Zweegman Sonja , Vellenga Edo , Croockewit Sandra , van Oers Marinus H. , von dem Borne Peter , Wijermans Pierre , Schaafsma Ron , de Weerdt Okke , Wittebol Shulamiet , Delforge Michel , Berenschot Henriëtte , Bos Gerard M. , Jie Kon-Siong G. , Sinnige Harm , van Marwijk-Kooy Marinus , Joosten Peter , Minnema Monique C. , van Ammerlaan Rianne , Sonneveld Pieter ,   for Dutch-Belgian Hemato-Oncology Group (HOVON)
Published: October 2009

The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m2, followed by maintenance with α-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P < .001), and prolonged progression free from median 25 months to 34 months (P < .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www.controlled-trials.com as ISRCTN06413384.
Methods for therapeutic trials in COPD: lessons from the TORCH trial
Authors: Keene O. N. , Vestbo J. , Anderson J. A. , Calverley P. M. A. , Celli B. , Ferguson G. T. , Jenkins C. , Jones P. W.
Published: October 2009

The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation.

When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments.

The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study.

Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.
Global gene expression patterns in the post-pneumonectomy lung of adult mice
Authors: Paxson Julia A , Parkin Christopher D , Iyer Lakshmanan K , Mazan Melissa R , Ingenito Edward P , Hoffman Andrew M
Published: October 2009

Background

Adult mice have a remarkable capacity to regenerate functional alveoli following either lung resection or injury that exceeds the regenerative capacity observed in larger adult mammals. The molecular basis for this unique capability in mice is largely unknown. We examined the transcriptomic responses to single lung pneumonectomy in adult mice in order to elucidate prospective molecular signaling mechanisms used in this species during lung regeneration.

Methods

Unilateral left pneumonectomy or sham thoracotomy was performed under general anesthesia (n = 8 mice per group for each of the four time points). Total RNA was isolated from the remaining lung tissue at four time points post-surgery (6 hours, 1 day, 3 days, 7 days) and analyzed using microarray technology.

Results

The observed transcriptomic patterns revealed mesenchymal cell signaling, including up-regulation of genes previously associated with activated fibroblasts (Tnfrsf12a, Tnc, Eln, Col3A1), as well as modulation of Igf1-mediated signaling. The data set also revealed early down-regulation of pro-inflammatory cytokine transcripts and up-regulation of genes involved in T cell development/function, but few similarities to transcriptomic patterns observed during embryonic or post-natal lung development. Immunohistochemical analysis suggests that early fibroblast but not myofibroblast proliferation is important during lung regeneration and may explain the preponderance of mesenchymal-associated genes that are over-expressed in this model. This again appears to differ from embryonic alveologenesis.

Conclusion

These data suggest that modulation of mesenchymal cell transcriptome patterns and proliferation of S100A4 positive mesenchymal cells, as well as modulation of pro-inflammatory transcriptome patterns, are important during post-pneumonectomy lung regeneration in adult mice.
Ethanol exerts dual effects on calcium homeostasis in CCK-8-stimulated mouse pancreatic acinar cells
Authors: Fernández-Sánchez Marcela , del Castillo-Vaquero Angel , Salido Ginés M , González Antonio
Published: October 2009

Background

A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively.

Results

Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 μM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production.

Conclusion

ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.
Pollen development in Annona cherimola Mill. (Annonaceae). Implications for the evolution of aggregated pollen
Authors: Lora Jorge , Testillano Pilar S , Risueño Maria C , Hormaza Jose I , Herrero Maria
Published: October 2009

Background

In most flowering plants, pollen is dispersed as monads. However, aggregated pollen shedding in groups of four or more pollen grains has arisen independently several times during angiosperm evolution. The reasons behind this phenomenon are largely unknown. In this study, we followed pollen development inAnnona cherimola, a basal angiosperm species that releases pollen in groups of four, to investigate how pollen ontogeny may explain the rise and establishment of this character. We followed pollen development using immunolocalization and cytochemical characterization of changes occurring from anther differentiation to pollen dehiscence.

Results

Our results show that, following tetrad formation, a delay in the dissolution of the pollen mother cell wall and tapetal chamber is a key event that holds the four microspores together in a confined tapetal chamber, allowing them to rotate and then bind through the aperture sites through small pectin bridges, followed by joint sporopollenin deposition.

Conclusion

Pollen grouping could be the result of relatively minor ontogenetic changes beneficial for pollen transfer or/and protection from desiccation. Comparison of these events with those recorded in the recent pollen developmental mutants in Arabidopsis indicates that several failures during tetrad dissolution may convert to a common recurring phenotype that has evolved independently several times, whenever this grouping conferred advantages for pollen transfer.
Comparison of breast cancer survival in two populations: Ardabil, Iran and British Columbia, Canada
Authors: Sadjadi Alireza , Hislop T Gregory , Bajdik Chris , Bashash Morteza , Ghorbani Anahita , Nouraie Mehdi , Babaei Masoud , Malekzadeh Reza , Yavari Parvin
Published: October 2009

Background

Patterns in survival can provide information about the burden and severity of cancer, help uncover gaps in systemic policy and program delivery, and support the planning of enhanced cancer control systems. The aim of this paper is to describe the one-year survival rates for breast cancer in two populations using population-based cancer registries: Ardabil, Iran, and British Columbia (BC), Canada.

Methods

All newly diagnosed cases of female breast cancer were identified in the Ardabil cancer registry from 2003 to 2005 and the BC cancer registry for 2003. The International Classification of Disease for Oncology (ICDO) was used for coding cancer morphology and topography. Survival time was determined from cancer diagnosis to death. Age-specific one-year survival rates, relative survival rates and weighted standard errors were calculated using life-tables for each country.

Results

Breast cancer patients in BC had greater one-year survival rates than patients in Ardabil overall and for each age group under 60.

Conclusion

These findings support the need for breast cancer screening programs (including regular clinical breast examinations and mammography), public education and awareness regarding early detection of breast cancer, and education of health care providers.
Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2genes in yeast
Authors: Vogelsang Matjaz , Comino Aleksandra , Zupanec Neja , Hudler Petra , Komel Radovan
Published: October 2009

Background

Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells.

Methods

Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested.

Results

The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic.

Conclusion

Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.
The development of 3-D, in vitro, endothelial culture models for the study of coronary artery disease
Authors: Farcas Monica A , Rouleau Leonie , Fraser Richard , Leask Richard L
Published: October 2009

The response of the vascular endothelium to wall shear stress plays a central role in the development and progression of atherosclerosis. Current studies have investigated endothelial response using idealized in vitro flow chambers. Such cell culture models are unable to accurately replicate the complex in vivo wall shear stress patterns arising from anatomical geometries. To better understand this implication, we have created both simplified/tubular and anatomically realistic in vitro endothelial flow models of the human right coronary artery. A post-mortem vascular cast of the human left ventricular outflow tract was used to create geometrically accurate silicone elastomer models. Straight, tubular models were created using a custom made mold. Following the culture of human abdominal aortic endothelial cells within the inner lumen, cells were exposed to steady flow (Re = 233) for varying time periods. The resulting cell morphology was analyzed in terms of shape index and angle of orientation relative to the flow direction. In both models a progressive elongation and alignment of the endothelium in the flow direction was observed following 8, 12, and 24 hours. This change, however, was significantly less pronounced in the anatomical model (as observed from morphological variations indicative of localized flow features). Differences were also observed between the inner and outer walls at the disease-prone proximal region. Since morphological adaptation is a visual indication of endothelial shear stress activation, the use of anatomical models in endothelial genetic and biochemical studies may offer better insight into the disease process.
The first Swedish H1N2 swine influenza virus isolate represents an uncommon reassortant
Authors: Bálint Ádám , Metreveli Giorgi , Widén Frederik , Zohari Siamak , Berg Mikael , Isaksson Mats , Renström Lena HM , Wallgren Per , Belák Sándor , Segall Thomas , Kiss István
Published: October 2009

The European swine influenza viruses (SIVs) show considerable diversity comprising different types of H1N1, H3N2, and H1N2 strains. The intensifying full genome sequencing efforts reveal further reassortants within these subtypes. Here we report the identification of an uncommon reassortant variant of H1N2 subtype influenza virus isolated from a pig in a multisite herd where H1N2 swine influenza was diagnosed for the first time in Sweden during the winter of 2008-2009. The majority of the European H1N2 swine influenza viruses described so far possess haemagglutinin (HA) of the human-like H1N2 SIV viruses and the neuraminidase (NA) of either the European H1N2 or H3N2 SIV-like viruses. The Swedish isolate has an avian-like SIV HA and a H3N2 SIV-like NA, which is phylogenetically more closely related to H3N2 SIV NAs from isolates collected in the early '80s than to the NA of H3N2 origin of the H1N2 viruses isolated during the last decade, as depicted by some German strains, indicative of independent acquisition of the NA genes for these two types of reassortants. The internal genes proved to be entirely of avian-like SIV H1N1 origin. The prevalence of this SIV variant in pig populations needs to be determined, as well as the suitability of the routinely used laboratory reagents to analyze this strain.

The description of this H1N2 SIV adds further information to influenza epidemiology and supports the necessity of surveillance for influenza viruses in pigs.
Neuroprotective effects of blockers for T-type calcium channels
Authors: Wildburger Norelle C , Lin-Ye Avary , Baird Michelle A , Lei Debin , Bao Jianxin
Published: October 2009

Cognitive and functional decline with age is correlated with deregulation of intracellular calcium, which can lead to neuronal death in the brain. Previous studies have found protective effects of various calcium channel blockers in pathological conditions. However, little has been done to explore possible protective effects of blockers for T-type calcium channels, which forms a family of FDA approved anti-epileptic drugs. In this study, we found that neurons showed an increase in viability after treatment with either L-type or T-type calcium channel antagonists. The family of low-voltage activated, or T-type calcium channels, comprise of three members (Cav3.1, Cav3.2, and Cav3.3) based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. Among these three subunits, α1H is highly expressed in hippocampus and certain cortical regions. However, T-type calcium channel blockers can protect neurons derived from α1H-/- mice, suggesting that neuroprotection demonstrated by these drugs is not through the α1H subunit. In addition, blockers for T-type calcium channels were not able to confer any protection to neurons in long-term cultures, while blockers of L-type calcium channels could protect neurons. These data indicate a new function of blockers for T-type calcium channels, and also suggest different mechanisms to regulate neuronal survival by calcium signaling pathways. Thus, our findings have important implications in the development of new treatment for age-related neurodegenerative disorders.
Self-harm in adolescents
Authors: Wood Alison
Published: October 2009

Self-harm in adolescents is common and is increasing. It can present to professionals as a symptom of major mental health disturbance or it can form part of a cultural ‘norm’. This article reviews current knowledge about self-harm in 12- to 18-year-olds. Definitions of self-harming behaviour, epidemiological and aetiological factors, risk assessment and management of self-harming in various settings are discussed in terms of pragmatic clinical approaches and evidence-based practice.
The role of the medical director in mental health
Authors: Deuchar Neil , Atkinson Elizabeth
Published: October 2009

This article sets out the history of medical directorship, outlines the authors' view of the current contribution that medical directors can and should be making to the mental health arena and looks forward to the possibilities of this evolving role. The focus of the article is mainly on English policy and healthcare structures, recognising that these vary in the other jurisdictions of the UK. However, certain principles should be of wider interest and application.
Ups and downs of intestinal function with prolonged fasting during aestivation in the burrowing frog, Cyclorana alboguttata
Authors: Cramp Rebecca L. , Kayes Sara M. , Meyer Edward A. , Franklin Craig E.
Published: October 2009

Although green striped burrowing frogs (Cyclorana alboguttata)experience large reductions in the mass and absorptive surface area of the small intestine (SI) during aestivation, little is known about how this may affect the functional capacity of the SI. We examined changes in the function(l-proline uptake rate and capacity) and metabolism of the SI(in vitro oxygen consumption, Na+/K+-ATPase activity and abundance) of C. alboguttata following 6 months of aestivation. l-Proline uptake rate was significantly higher in aestivating frogs, but overall uptake capacity was lower than in active frogs. Total SI oxygen consumption rate (VO2) was also lower in aestivating frogs, despite no difference in mass-specific V̇O2. The proportion of intestinal V̇O2 associated with Na+/K+-ATPase activity and protein synthesis was equivalent between active and aestivating frogs, suggesting these processes were unaffected by aestivation. Indeed, the activity of Na+/K+-ATPase transporters in the SI of aestivating frogs was not different from that of active animals. Aestivating frogs maintained Na+/K+-ATPase activity, despite experiencing a reduction in the density of Na+/K+-ATPase transporters, by increasing the molecular activity of the remaining pumps to 2–3 times that of active frogs. These results show that functionality of the SI is maintained at the cellular level, potentially facilitating the reclamation of nutrients from the intestinal lumen while in aestivation. Despite this, the functional capacity of the SI in aestivating C. alboguttata is significantly reduced due to a reduction in tissue mass,helping frogs to conserve energy while in aestivation.