bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients’ Preferences for Treatment of Hepatitis C
Authors: Fraenkel Liana , Chodkowski Diane , Lim Joseph , Garcia-Tsao Guadalupe
Published: July 2009

Background. The objective of this study was to ascertain patient preferences for treatment of hepatitis C virus (HCV). Methods. The authors recruited consecutive patients eligible for treatment of HCV and used adaptive conjoint analysis (ACA), a hybrid approach of conjoint analysis that uses both self-explicated ratings and pair-wise comparisons, to elicit preferences for pegylated-interferon and ribavirin. They examined the association between patient characteristics and treatment preferences using the Mann-Whitney U test and χ2 statistic for continuous and categorical variables, respectively, and subsequently calculated adjusted odds ratios and 95% confidence intervals using logistic regression. Results. A total of 140 subjects completed the ACA task. The mean (±SD) age of the sample was 51±8 y; 85% were male, and 59% were white. When described as being associated with mild side effects, 67% (n = 94) of subjects preferred treatment for HCV. The percentage of subjects preferring therapy decreased to 51% (n = 72) when it was described as being associated with severe side effects. Preferences for treatment of HCV were stronger among subjects with a higher perceived risk of developing cirrhosis, more severe underlying liver disease, and worse HCV-related quality of life. Subjects having more severe disease placed greater weight on the importance of expected benefits and less on the risk of toxicity compared with those with mild or no fibrosis. Conclusions. Whether to choose treatment for HCV is a difficult decision for many patients. Treatment is usually recommended for those with moderate to severe liver disease, and these results demonstrate that most patients’ preferences are concordant with this practice. Key words: hepatitis C; decision making; pegylated-interferon; ribavirin. (Med Decis Making 2010;30:45—57)
Protestant Work Ethic Endorsement and Social Justice Values in Developing and Developed Societies
Authors: Frey Rosemary Ann , Powell Lawrence Alfred
Published: July 2009

Taking Weber's Protestant Ethic and the Spirit of Capitalism thesis as the point of departure, this paper compares work ethic endorsement patterns and social justice correlates in a developing society, Jamaica, and a developed society, New Zealand. A condensed version of Mirels and Garrett's Protestant work ethic scale and related demographic and social values-related measures were administered at Jamaican and New Zealand universities. High and low Protestant ethic (PE) clusters were isolated, within each culture, among comparable samples of undergraduate social science students, and multiple analysis of variance applied to test effects of culture, Protestant religious affiliation and related “social justice values” variables (welfare state support, redistribution, intergenerational equity, free enterprise, social distance from the disadvantaged, social Darwinism). Results suggest there are significant cultural differences between high and low PE scorers on key justice-related societal values often seen as being associated with the Protestant work ethic. Possible reasons for the differences are advanced in light of Jamaican and New Zealand social and political conditions.
Reward and Punishment Allocation in the Indian Culture
Authors: Krishnan Lilavati , Varma Premlata , Pandey Vijyendra
Published: July 2009

Two scenario studies examined justice perceptions in Indian samples. Study 1 investigated the effect of allocator-recipient relationship and internal/external locus of merit and need on both reward and punishment allocation in a distributive context, involving a meritorious and a needy recipient. Between merit, need and equality, subjects showed a clear equality orientation, in both allocation rule preference and perceived fairness of a given allocation. This finding was inconsistent with the strong need orientation reported in several Indian studies. In order to obtain more information on punishment alone, Study 2 was conducted in order to investigate a non-distributive context, involving internal/external locus of merit and need, and choice of punishment and perceived fairness of a given set of punishments, seriousness of the offence, guilt of the offender and the importance of need and merit. In both studies, the effect of situational variables did not emerge as expected. The apparent absence of effects of the situational variables was interpreted as the expression of a cognitive strategy to combine all the contextual information. The equality orientation found in Study 1 was interpreted as the resultant of such a combination. One part of this combination was in terms of the merit and need rules. It was suggested that subjects thought in terms of merit and need, instead of merit or need. Some evidence for this suggestion was obtained in Study 2. Need and merit were rated as being similar in importance when deciding a fair punishment. Attention was drawn to several aspects of justice perception, especially those related to punishment that requires further detailed investigation with modified methods.
Mind and Body Management Strategies for Chronic Pain and Rheumatoid Arthritis
Authors: Shariff Fauzia , Carter Jane , Dow Clare , Polley Marie , Salinas Maria , Ridge Damien
Published: July 2009

Chronic pain (CP) and rheumatoid arthritis (RA) pose particular challenges for the individual. Although biomedicine inevitably plays a role in the reduction or control of some symptoms for people living with chronic pain, directed self-management is also increasingly recognized as an important tool. Self-management can address pain-associated symptoms of CP and RA, and often has broader aims, such as promoting positive well-being. Forty-six interviews with people experiencing CP and 46 interviews with those living with RA-associated pain were analyzed. Our analysis uncovered three broad strategies adopted by participants: body management, mind-management and mindbody management. The analysis demonstrated that for those living with pain, a sense of well-being is achieved not through pain control alone, but also through various mind/body techniques for managing pain, accepting new limits, and adjusting the way people relate to themselves. These self-management strategies are an important adjunct to biomedical care for those experiencing chronic pain.
Intuition, Subjectivity, and Le Bricoleur: Cancer Patients' Accounts of Negotiating a Plurality of Therapeutic Options
Authors: Broom Alex
Published: July 2009

Cancer patients are now combining complementary and alternative medicine (CAM) with biomedical cancer treatments, reflecting an increasingly pluralistic health care environment. However, there has been little research done on the ways in which cancer patients juggle multiplicity in claims to expertise, models of disease, and therapeutic practice. Drawing on the accounts of cancer patients who use CAM, in this article I develop a conceptualization of therapeutic decision making, utilizing the notion of bricolage as a key point of departure. The patient accounts illustrate the “piecing together” (or bricolage) of therapeutic trajectories, drawing on intuitive, embodied knowledge, as well as formalized “objective” scientific expertise. Le bricoleur, as characterized here, actively mediates, rather than accepts or rejects CAM or biomedicine, and utilizes a combination of scientific expertise, embodied physicality, and social knowledge to make decisions and assess therapeutic effectiveness. Although these “border crossings” are potentially subversive of established biomedical expertise, the analysis also illustrates the structural constraints (and penalties) associated with bricolage, and furthermore, the interplay of a repositioning of responsibility with neoliberal forms of self-governance.
Coping With HIV: Caribbean People in the United Kingdom
Authors: Anderson Moji , Elam Gillian , Solarin Ijeoma , Gerver Sarah , Fenton Kevin , Easterbrook Philippa
Published: July 2009

Although Caribbean people in the United Kingdom are increasingly being affected by HIV/AIDS, there has been no examination of how they are coping with the illness. We investigate the coping strategies of HIV-positive Caribbean people using in-depth interviews with a purposively selected group of 25 residents of South London. The main coping strategies were more cognitive than behavioral: restricted disclosure, submersion, faith, and positive reappraisal. These strategies were intertwined in complex ways, and most were rooted in contextual factors, particularly cultural ones. Themes of loss, silence, and reinvention suffused respondents' narratives. Interventions should consider the high degree of stigmatization of HIV/AIDS in the Caribbean community, reluctance to disclose, the likelihood of an initial severe reaction to diagnosis, and external stressors. HIV-positive Caribbean people who are coping well could serve as mentors and role models for poor copers and newly diagnosed patients; establishing Caribbean-specific support groups might also assist coping.
Making New Meanings of Being in the World After Treatment for Oral Cancer
Authors: Röing Marta , Hirsch Jan-Michaél , Holmström Inger , Schuster Marja
Published: July 2009

When the mouth is affected by cancer, difficulties in satisfying basic human needs such as eating, tasting, swallowing, and speaking might arise, and the existential significance of the mouth might become obvious. How does it feel to live with these difficulties? What does it mean to be a human being living with the consequences of oral cancer? Five patients with oral cancer were interviewed a median time of 4 years after the beginning of treatment. A hermeneutic research approach was used to understand, explain, and interpret the transcribed interviews and showed how the consequences of oral cancer affected the being-in-the-world of the participants in three ways: existing as oneself, existing in the eyes of others, and existing with others. Against the background of the philosophy of Martin Heidegger, these findings illuminate how essential the mouth is to a human being's identity and existence.
Hospitalization for Type 2 Diabetes: The Effects of the Suspension of Reality on Patients' Subsequent Management of Their Condition
Authors: Balcou-Debussche Maryvette , Debussche Xavier
Published: July 2009

Hospitalization still plays a major part in the management of uncontrolled type 2 diabetes and its complications. In this article, we assess the effects of self-management education on the individual practices of 42 patients after discharge from specialized diabetes units on the French island of Reunion. Hospitalization offers respite and temporarily suspends the realities of daily life. When patients leave the unit where they have acquired new knowledge and practices, the extent to which the latter can be maintained depends on the practice in question, the individual's circumstances, and his or her social relationships and support systems. In the longer term, therefore, the effects of self-management education interventions can be weak. The study findings reveal the complexities surrounding the acquisition of habits that maintain health and prevent illness. The article makes a significant contribution to the debate on patient support and the role of inpatient educational units.
Experiencing Cancer in Old Age: A Qualitative Systematic Review
Authors: Hughes Nic , Closs S. José , Clark David
Published: July 2009

Our purpose in this study was to find, report, and interpret the results of qualitative studies which investigated the experiences of older people living with cancer. We conducted systematic literature searches, identified and extracted the findings from 11 studies, and analyzed them systematically. We interpreted the findings to suggest that living with cancer in old age is to live in a perpetual state of ambiguity. The experience is characterized by a sense of disintegration, diminished identity, suffering, and social retraction. These experiences are balanced by sources of comfort and strength found within the self and among diverse relationships. The results of our study illuminate the complex, multidimensional character of living with cancer in old age. They show that older people living with cancer are resilient as well as vulnerable. We argue for changes in attitudes and behavior that will enable health care professionals to foster older peoples' resilience.
Making Sense of Living Under the Shadow of Death: Adjusting to a Recurrent Breast Cancer Illness
Authors: Kenne Sarenmalm Elisabeth , Thorén-Jönsson Anna-Lisa , Gaston-Johansson Fannie , Öhlén Joakim
Published: July 2009

Women with recurrent breast cancer face many difficulties and challenges, from clinical symptoms of disease progression and treatment to a range of emotional responses. Guided by grounded theory methodology, we explored the main concerns of women with recurrent breast cancer, and how they were dealing with their situations. Data were collected from 40 in-depth interviews with 20 women diagnosed with recurrent breast cancer. The core category illustrated the process of “making sense of living under the shadow of death,” and was based on the women's experiences of adjusting to living with a persistent life-threatening illness. Confronting a recurrence of breast cancer was a life-altering event. Moving through a difficult and challenging time, women eased their distress by letting go of losses and reassessing important values. Through a personal transition women transcended living with a life-threatening illness. These findings emphasize the importance of recognizing existential distress in clinical practice.
Distributed Leadership in Higher Education: What Does It Accomplish?
Authors: Gosling Jonathan , Bolden Richard , Petrov Georgy
Published: July 2009

The term `distributed leadership' has been prominent in research into educational management for some time. A number of articles have recently questioned the explanatory utility of the concept; in this article we examine its rhetorical function in higher education institutions. We suggest that it has served to contain, and to some extent ameliorate, two contradictions in the experience of academics who take on managerial roles or who exert leadership of some sort. First, it may help to make sense of a contrast between their experience of leadership and their sense of what it should be; second, it helps to mediate conflicts in the identity-work of being an academic and a manager. Also, placed in the wider context of changes in the cultures of universities, `distributed leadership' masks the concentration of influence with those who have control of budgets, and simultaneous threats to traditional means of upward communication, and the predominance of academic leadership. We conclude that the term `distributed leadership' draws attention to the large number of actors involved in leadership, and the importance of organizational processes in shaping their engagements, but has limited use as an analytical heuristic. However, it has a number of rhetorical functions that make a significant contribution to the ways in which leadership is accomplished in sectors such as higher education.
Leadership Researchers on Leadership in Higher Education
Authors: Bryman Alan , Lilley Simon
Published: July 2009

This article reports the findings of a study in which leadership researchers were interviewed regarding their experiences and perceptions of leadership in higher education institutions. In particular, the research was concerned with the types of leadership associated with effectiveness, particularly at the Head of Department level. While several forms of leadership were identified as likely to be effective and ineffective, no single type of leadership stood out. The authors consider the implications of the findings for the development of leadership competency frameworks, noting in particular that interviewees tended to be sceptical about them because the frameworks tend to underestimate the significance of contextual factors. The authors also consider why it may be that many of the issues identified from the interview transcripts relate to well-known established themes.
`Blended Leadership': Employee Perspectives on Effective Leadership in the UK Further Education Sector
Authors: Collinson David , Collinson Margaret
Published: July 2009

This article explores employee perspectives on effective leadership in UK Further Education (FE). Studies on leadership effectiveness typically seek either to specify the individual qualities of `heroic' leaders or, increasingly, to highlight the collective nature of `post-heroic' leadership. While these discourses are frequently seen as dichotomous and competing, our research found that FE employees often value practices that combine elements of both. They tended to prefer subtle and versatile practices that we term `blended leadership'; an approach that values, for example, both delegation and direction, both proximity and distance and both internal and external engagement. Drawing on other studies which indicate that paradoxical blends of apparently irreconcilable opposites might form the basis for effective leadership, the article considers the implications of this analysis for the study of Higher Education (HE). It concludes by highlighting the potential value of more dialectical approaches to the theory and practice of leadership.
Pulmonary effects of nebivolol
Authors: Dal Negro Roberto
Published: July 2009

The pharmacological control of arterial hypertension is a very frequent issue in clinical practice and some critical aspects can arise in particular circumstances and with particular molecules. In the case of hypertensive subjects with respiratory comorbidities, when first introduced, these β-adrenergic receptor antagonists were described as affecting airway patency as a result of their antagonism against β2-adrenergic receptors within airway muscles. New molecules with a better respiratory tolerability were subsequently designed in order to overcome the narrow therapeutic window of first-generation β-adrenergic receptor antagonists. Nebivolol is a third-generation β-adrenergic receptor antagonist with high β1-selective adrenergic receptor antagonism and vasodilating properties that induces a substantial decrease of arterial pressure in hypertensive subjects while preserving their left ventricular function. Respiratory effects of nebivolol have been investigated in animal models, in healthy volunteers and in clinical trials carried out on patients suffering from bronchial asthma and chronic obstructive pulmonary disease (COPD). In contrast to older compounds, nebivolol, which modulates the endogenous production of nitric oxide and affects oxidative cascade, proved clinically well tolerated in terms of respiratory outcomes in this type of subject. Moreover, due to the substantial dissociation between its cardiac and pulmonary activity, nebivolol confirmed a very good safety profile when regularly administered to hypertensive subjects with obstructive respiratory comorbidities.
To Hedge or Not to Hedge
Authors: Chang Charles
Published: July 2009

This article studies whether foreign exchange risk can be reduced by operational controls. Specifically, revenue management practices for five international markets are analyzed over a period of more than six years. Results show that ADR (average daily rate), RevPAR (revenue per available room), and occupancy improve in weak currency environments to make up for losses resulting from currency translation. The reverse is also true. That is, occupancy declines in strong currency environments to make up for gains in exchange. In other words, when a weak local currency threatens dollar-denominated earnings, managers can make up for it by increasing ADR without reducing occupancy, thereby increasing RevPAR. The result is significantly less exposure to foreign exchange risk than implied by traditional hedging arguments.
Carbon monoxide gas-sensing properties of CeO2–WO3 thin films
Authors: Al-Kuhaili M. F. , Durrani S. M. A. , Bakhtiari I. A.
Published: July 2009

Mixed films of cerium oxide (CeO2) and tungsten oxide (WO3) were deposited on unheated substrates by co-evaporation. The films were annealed in air at 500°C for 2 h. The surface morphology of the films was characterised using atomic force microscopy. The chemical composition was determined using X-ray photoelectron spectroscopy. The optical properties were derived from normal incidence reflectance and transmittance measurements. The films were investigated for the detection of carbon monoxide. The effects of the operating temperature and gas concentration on the performance of the sensor were investigated. The sensor response and recovery times were also measured.
Low cycle fatigue behaviour of hot extruded Al–4Mg–1Nd alloy
Authors: Chen L. J. , Wang X. , Ma C. Y. , Che X.
Published: July 2009

The low cycle fatigue behaviour of the hot extruded Al–4Mg–1Nd alloy has been investigated under those total strain amplitudes ranged from 0·3 to 1·2% at room temperature. The results of the low cycle fatigue experiments show that during the fatigue deformation, the significant cyclic strain hardening and stable cyclic stress response can be noted for the hot extruded Al–4Mg–1Nd alloy. The relationship between elastic and plastic strain amplitudes with reversals to failure shows a monotonic linear behaviour, and can be described by the Basquin and Coffin–Manson equations respectively. It is also observed that at the higher total strain amplitudes of 0·8 to 1·2%, the so called dynamic strain aging takes place during the fatigue deformation of hot extruded Al–4Mg–1Nd alloy. In addition, the observations on the fracture surfaces reveal that under the low cycle fatigue loading condition, the fatigue cracks initiate transgranularly at the free surface of fatigue specimens and propagate in a transgranular mode.
Long-term protection from syngeneic acute lymphoblastic leukemia by CpG ODN-mediated stimulation of innate and adaptive immune responses
Authors: Seif Alix E. , Barrett David M. , Milone Michael , Brown Valerie I. , Grupp Stephan A. , Reid Gregor S. D.
Published: July 2009

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and remains a major cause of mortality in children with recurrent disease and in adults. Despite observed graft-versus-leukemia effects after stem cell transplantation, successful immune therapies for ALL have proven elusive. We previously reported immunostimulatory oligodeoxynucleotides containing CpG motifs (CpG ODN) enhance allogeneic Th1 responses and reduce leukemic burden of primary human ALL xenografts. To further the development of CpG ODN as a novel ALL therapy, we investigated the antileukemia activity induced by CpG ODN in a transplantable syngeneic pre-B ALL model. CpG ODN induced early killing of leukemia by innate immune effectors both in vitro and in vivo. Mice were treated with CpG ODN starting 7 days after injection with leukemia to mimic a minimal residual disease state and achieved T cell–dependent remissions of more than 6 months. In addition, mice in remission after CpG ODN treatment were protected from leukemia rechallenge, and adoptive transfer of T cells from mice in remission conferred protection against leukemia growth. To our knowledge, this is the first demonstration that CpG ODN induce a durable remission and ongoing immune-mediated protection in ALL, suggesting this treatment may have clinical utility in patients with minimal residual disease.
The microenvironment in mature B-cell malignancies: a target for new treatment strategies
Authors: Burger Jan A. , Ghia Paolo , Rosenwald Andreas , Caligaris-Cappio Federico
Published: July 2009

Despite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.
Modulation of lung inflammation by vessel dilator in a mouse model of allergic asthma
Authors: Wang Xiaoqin , Xu Weidong , Kong Xiaoyuan , Chen Dongqing , Hellermann Gary , Ahlert Terry A , Giaimo Joseph D , Cormier Stephania A , Li Xu , Lockey Richard F , Mohapatra Subhra , Mohapatra Shyam S
Published: July 2009

Background

Atrial natriuretic peptide (ANP) and its receptor, NPRA, have been extensively studied in terms of cardiovascular effects. We have found that the ANP-NPRA signaling pathway is also involved in airway allergic inflammation and asthma. ANP, a C-terminal peptide (amino acid 99–126) of pro-atrial natriuretic factor (proANF) and a recombinant peptide, NP73-102 (amino acid 73–102 of proANF) have been reported to induce bronchoprotective effects in a mouse model of allergic asthma. In this report, we evaluated the effects of vessel dilator (VD), another N-terminal natriuretic peptide covering amino acids 31–67 of proANF, on acute lung inflammation in a mouse model of allergic asthma.

Methods

A549 cells were transfected with pVD or the pVAX1 control plasmid and cells were collected 24 hrs after transfection to analyze the effect of VD on inactivation of the extracellular-signal regulated receptor kinase (ERK1/2) through western blot. Luciferase assay, western blot and RT-PCR were also performed to analyze the effect of VD on NPRA expression. For determination of VD's attenuation of lung inflammation, BALB/c mice were sensitized and challenged with ovalbumin and then treated intranasally with chitosan nanoparticles containing pVD. Parameters of airway inflammation, such as airway hyperreactivity, proinflammatory cytokine levels, eosinophil recruitment and lung histopathology were compared with control mice receiving nanoparticles containing pVAX1 control plasmid.

Results

pVD nanoparticles inactivated ERK1/2 and downregulated NPRA expression in vitro, and intranasal treatment with pVD nanoparticles protected mice from airway inflammation.

Conclusion

VD's modulation of airway inflammation may result from its inactivation of ERK1/2 and downregulation of NPRA expression. Chitosan nanoparticles containing pVD may be therapeutically effective in preventing allergic airway inflammation.
Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice
Authors: Clement Cecilia G , Tuvim Michael J , Evans Christopher M , Tuvin Daniel M , Dickey Burton F , Evans Scott E
Published: July 2009

Background

Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria.

Methods

To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days.

Results

We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic. The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.

Conclusion

These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.
Multiple histone modifications in euchromatin promote heterochromatin formation by redundant mechanisms in Saccharomyces cerevisiae
Authors: Verzijlbergen Kitty F , Faber Alex W , Stulemeijer Iris JE , van Leeuwen Fred
Published: July 2009

Background

Methylation of lysine 79 on histone H3 by Dot1 is required for maintenance of heterochromatin structure in yeast and humans. However, this histone modification occurs predominantly in euchromatin. Thus, Dot1 affects silencing by indirect mechanisms and does not act by the recruitment model commonly proposed for histone modifications. To better understand the role of H3K79 methylation gene silencing, we investigated the silencing function of Dot1 by genetic suppressor and enhancer analysis and examined the relationship between Dot1 and other global euchromatic histone modifiers.

Result

We determined that loss of H3K79 methylation results in a partial silencing defect that could be bypassed by conditions that promote targeting of Sir proteins to heterochromatin. Furthermore, the silencing defect in strains lacking Dot1 was dependent on methylation of H3K4 by Set1 and histone acetylation by Gcn5, Elp3, and Sas2 in euchromatin. Our study shows that multiple histone modifications associated with euchromatin positively modulate the function of heterochromatin by distinct mechanisms. Genetic interactions between Set1 and Set2 suggested that the H3K36 methyltransferase Set2, unlike most other euchromatic modifiers, negatively affects gene silencing.

Conclusion

Our genetic dissection of Dot1's role in silencing in budding yeast showed that heterochromatin formation is modulated by multiple euchromatic histone modifiers that act by non-overlapping mechanisms. We discuss how euchromatic histone modifiers can make negative as well as positive contributions to gene silencing by competing with heterochromatin proteins within heterochromatin, within euchromatin, and at the boundary between euchromatin and heterochromatin.
Physical activity and diet behaviour in colorectal cancer patients receiving chemotherapy: associations with quality of life
Authors: Stephenson Lynette E , Bebb D Gwyn , Reimer Raylene A , Culos-Reed S Nicole
Published: July 2009

Background

The relationship between colorectal cancer (CRC) risk and physical activity and dietary habits has been well-established, but less is known about the relationship between these behaviours and quality of life (QOL) post-diagnosis. Moreover, it is unknown whether this relationship is consistent across cancer stage or treatment setting. Thus, the purpose of this study was to assess current diet and physical activity behaviour in CRC survivors receiving systemic chemotherapy, and to examine potential associations between these behaviours and quality of life. A secondary purpose was to examine the association between social support, diet, and physical activity behaviour in this population.

Methods

Using a cross-sectional survey, 67 CRC survivors currently receiving chemotherapy in Calgary, Alberta completed the survey package. Measures included demographic and medical data, physical activity levels, diet behaviour, QOL, and social support.

Results

In a largely metastatic sample (63%), approximately half were meeting national dietary guidelines (58%), less were meeting national physical activity guidelines (26%), and a small number were meeting both (17%). However, only 12.3% (n = 8) reported completely sedentary behaviour, and 7 of these 8 participants were receiving metastatic treatment. Neither behaviour was significantly associated with QOL or perceived social support. Furthermore, there were no significant QOL differences between those treated with palliative intent or adjuvant therapy. Important group differences emerged between those meeting and not meeting the guidelines, and associations between QOL, age, BMI, and provisions of social support.

Conclusion

These findings provide insight into lifestyle behaviours of CRC survivors currently receiving systemic chemotherapy, and the differences in perceived QOL as affected by severity of disease and treatment setting. Prospective studies in a larger sample of CRC survivors on chemotherapy are needed to confirm lifestyle behaviour patterns and identify factors related to QOL that are unique to this population, especially during metastatic treatment.
Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial)
Authors: Barraclough Katherine A , Noble Euan , Leary Diana , Brown Fiona , Hawley Carmel M , Campbell Scott B , Isbel Nicole M , Mudge David W , van Eps Carolyn L , Sturtevant Joanna M , Johnson David W
Published: July 2009

Background

The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin®ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet®).

Methods

Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp®, Amgen) for ≥ 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events).

Discussion

This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation.

Trial Registration

Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.
Risk factors for suicide in Hungary: a case-control study
Authors: Almasi Kitty , Belso Nora , Kapur Navneet , Webb Roger , Cooper Jayne , Hadley Sarah , Kerfoot Michael , Dunn Graham , Sotonyi Peter , Rihmer Zoltan , Appleby Louis
Published: July 2009

Background

Hungary previously had one of the highest suicide rates in the world, but experienced major social and economic changes from 1990 onwards. We aimed to investigate the antecedents of suicide in Hungary. We hypothesised that suicide in Hungary would be associated with both risk factors for suicide as identified in Western studies, and experiences related to social and economic restructuring.

Methods

We carried out a controlled psychological autopsy study. Informants for 194 cases (suicide deaths in Budapest and Pest County 2002–2004) and 194 controls were interviewed by clinicians using a detailed schedule.

Results

Many of the demographic and clinical risk factors associated with suicide in other settings were also associated with suicide in Hungary; for example, being unmarried or having no current relationship, lack of other social contacts, low educational attainment, history of self-harm, current diagnosis of affective disorder (including bipolar disorder) or personality disorder, and experiencing a recent major adverse life event. A number of variables reflecting experiences since economic restructuring were also associated with suicide; for example, unemployment, concern over work propects, changes in living standards, practising religion. Just 20% of cases with evidence of depression at the time of death had received antidepressants.

Conclusion

Suicide rates in Hungary are falling. Our study identified a number of risk factors related to individual-level demographic and clinical characteristics, and possibly recent societal change. Improved management of psychiatric disorder and self-harm may result in further reductions in suicide rates.
Respiratory physiotherapy and incidence of pulmonary complications in off-pump coronary artery bypass graft surgery: an observational follow-up study
Authors: Yánez-Brage Isabel , Pita-Fernández Salvador , Juffé-Stein Alberto , Martínez-González Ursicino , Pértega-Díaz Sonia , Mauleón-García Ángeles
Published: July 2009

Background

Heart surgery is associated with an occurrence of pulmonary complications. The aim of this study was to determine whether pre-surgery respiratory physiotherapy reduces the incidence of post-surgery pulmonary complications.

Methods

Observational study of 263 patients submitted to off-pump coronary artery bypass grafting (CABG) surgery at the A Coruña University Hospital (Spain). 159 (60.5%) patients received preoperative physiotherapy. The fact that patients received preoperative physiotherapy or not was related to whether they were admitted to the cardiac surgery unit or to an alternative unit due to a lack of beds.

A physiotherapist provided a daily session involving incentive spirometry, deep breathing exercises, coughing and early ambulation. A logistic regression analysis was carried out in order to identify variables associated with pulmonary complications.

Results

Both groups of patients (those that received physiotherapy and those that did not) were similar in age, sex, body mass index, creatinine, ejection fraction, number of affected vessels, O2basal saturation, prevalence of diabetes, dyslipidemia, exposure to tobacco, age at smoking initiation, number of cigarettes/day and number of years as a smoker. The most frequent postoperative complications were hypoventilation (90.7%), pleural effusion (47.5%) and atelectasis (24.7%).

In the univariate analysis, prophylactic physiotherapy was associated with a lower incidence of atelectasis (17% compared to 36%, p = 0.01).

After taking into account age, sex, ejection fraction and whether the patients received physiotherapy or not, we observed that receiving physiotherapy is the variable with an independent effect on predicting atelectasis.

Conclusion

Preoperative respiratory physiotherapy is related to a lower incidence of atelectasis.
Anti-microbial activities of pomegranate rind extracts: enhancement by cupric sulphate against clinical isolates of S. aureus, MRSA and PVL positive CA-MSSA
Authors: Gould Simon WJ , Fielder Mark D , Kelly Alison F , Naughton Declan P
Published: July 2009

Background

Recently, natural products have been evaluated as sources of antimicrobial agents with efficacies against a variety of micro-organisms.

Methods

This report describes the antimicrobial activities of pomegranate rind extract (PRE) singularly and in combination with cupric sulphate against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA, MRSA respectively), and Panton-Valentine Leukocidin positive community acquired MSSA (PVL positive CA-MSSA).

Results

PRE alone showed limited efficacy against MRSA and MSSA strains. Exposure to copper (II) ions alone for 2 hours resulted in moderate activity of between 102 to 103 log10 cfu mL-1 reduction in growth. This was enhanced by the addition of PRE to 104 log10 cfu mL-1 reduction in growth being observed in 80% of the isolates. However, the PVL positive CA-MSSA strains were more sensitive to copper (II) ions which exhibited moderate activities of between 103 log10 cfu mL-1 reduction in growth for 60% of the isolates.

Conclusion

PRE, in combination with Cu(II) ions, was seen to exhibit moderate antimicrobial effects against clinical isolates of MSSA, MRSA and PVL positive CA-MSSA isolates. The results of this study indicate that further investigation into the active ingredients of natural products, their mode of action and potential synergism with other antimicrobial agents is warranted. This is the first report of the efficacy of pomegranate against clinical PVL positive CA-MSSA isolates.
Regioselective biooxidation of (+)-valencene by recombinant E. coli expressing CYP109B1 from Bacillus subtilis in a two-liquid-phase system
Authors: Girhard Marco , Machida Kazuhiro , Itoh Masashi , Schmid Rolf D , Arisawa Akira , Urlacher Vlada B
Published: July 2009

Background

(+)-Nootkatone (4) is a high added-value compound found in grapefruit juice. Allylic oxidation of the sesquiterpene (+)-valencene (1) provides an attractive route to this sought-after flavoring. So far, chemical methods to produce (+)-nootkatone (4) from (+)-valencene (1) involve unsafe toxic compounds, whereas several biotechnological approaches applied yield large amounts of undesirable byproducts. In the present work 125 cytochrome P450 enzymes from bacteria were tested for regioselective oxidation of (+)-valencene (1) at allylic C2-position to produce (+)-nootkatone (4) via cis- (2) or trans-nootkatol (3). The P450 activity was supported by the co-expression of putidaredoxin reductase (PdR) and putidaredoxin (Pdx) from Pseudomonas putida in Escherichia coli.

Results

Addressing the whole-cell system, the cytochrome CYP109B1 from Bacillus subtilis was found to catalyze the oxidation of (+)-valencene (1) yielding nootkatol (2 and 3) and (+)-nootkatone (4). However, when the in vivo biooxidation of (+)-valencene (1) with CYP109B1 was carried out in an aqueous milieu, a number of undesired multi-oxygenated products has also been observed accounting for approximately 35% of the total product. The formation of these byproducts was significantly reduced when aqueous-organic two-liquid-phase systems with four water immiscible organic solvents – isooctane, n-octane, dodecane or hexadecane – were set up, resulting in accumulation of nootkatol (2 and 3) and (+)-nootkatone (4) of up to 97% of the total product. The best productivity of 120 mg l-1 of desired products was achieved within 8 h in the system comprising 10% dodecane.

Conclusion

This study demonstrates that the identification of new P450s capable of producing valuable compounds can basically be achieved by screening of recombinant P450 libraries. The biphasic reaction system described in this work presents an attractive way for the production of (+)-nootkatone (4), as it is safe and can easily be controlled and scaled up.
A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR – implications for therapeutic failure and drug resistance
Authors: Sengaloundeth Sivong , Green Michael D , Fernández Facundo M , Manolin Ot , Phommavong Khamlieng , Insixiengmay Vongsavanh , Hampton Christina Y , Nyadong Leonard , Mildenhall Dallas C , Hostetler Dana , Khounsaknalath Lamphet , Vongsack Latsamy , Phompida Samlane , Vanisaveth Viengxay , Syhakhang Lamphone , Newton Paul N
Published: July 2009

Background

Counterfeit oral artesunate has been a major public health problem in mainland SE Asia, impeding malaria control. A countrywide stratified random survey was performed to determine the availability and quality of oral artesunate in pharmacies and outlets (shops selling medicines) in the Lao PDR (Laos).

Methods

In 2003, 'mystery' shoppers were asked to buy artesunate tablets from 180 outlets in 12 of the 18 Lao provinces. Outlets were selected using stratified random sampling by investigators not involved in sampling. Samples were analysed for packaging characteristics, by the Fast Red Dye test, high-performance liquid chromatography (HPLC), mass spectrometry (MS), X-ray diffractometry and pollen analysis.

Results

Of 180 outlets sampled, 25 (13.9%) sold oral artesunate. Outlets selling artesunate were more commonly found in the more malarious southern Laos. Of the 25 outlets, 22 (88%; 95%CI 68–97%) sold counterfeit artesunate, as defined by packaging and chemistry. No artesunate was detected in the counterfeits by any of the chemical analysis techniques and analysis of the packaging demonstrated seven different counterfeit types. There was complete agreement between the Fast Red dye test, HPLC and MS analysis. A wide variety of wrong active ingredients were found by MS. Of great concern, 4/27 (14.8%) fakes contained detectable amounts of artemisinin (0.26–115.7 mg/tablet).

Conclusion

This random survey confirms results from previous convenience surveys that counterfeit artesunate is a severe public health problem. The presence of artemisinin in counterfeits may encourage malaria resistance to artemisinin derivatives. With increasing accessibility of artemisinin-derivative combination therapy (ACT) in Laos, the removal of artesunate monotherapy from pharmacies may be an effective intervention.