Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.

Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.

Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.

Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Maintenance of the gag/gag-pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity

Production of the human immunodeficiency virus type 1 (HIV_-1) Gag-Pol precursor protein results from a −1 ribosomal frameshifting event. In infected cells, this generates Gag and Gag-Pol in a ratio that is estimated to be 20:1, a ratio that is conserved among retroviruses. To examine the impact of this ratio on HIV_-1 replication and viral assembly, we altered the Gag/Gag-Pol ratio in virus-producing cells by cotransfecting HIV_-1 proviral DNA with an HIV_-1 Gag-Pol expression vector. Two versions of the Gag-Pol expression vector were used; one contains an active protease [PR(+)], and the other contains an inactive protease [PR(−)]. In an attempt to produce viral particles with Gag/Gag-Pol ratios ranging from 20:21 to 20:1 (wild type), 293T cells were cotransfected with various ratios of wild-type proviral DNA and proviral DNA from either Gag-Pol expression vector. Viral particles derived from cells with altered Gag/Gag-Pol ratios via overexpression of PR(−) Gag-Pol showed a ratio-dependent defect in their virion protein profiles. However, the defects in virion infectivity were independent of the nature of the Gag-Pol expression vector, i.e., PR(+) or PR(−). Based on equivalent input of reverse transcriptase activity, we estimated that HIV_-1 infectivity was reduced 250- to 1,000-fold when the Gag/Gag-Pol ratio in the virion-producing cells was altered from 20:1 to 20:21. Although virion RNA packaging was not affected by altering Gag/Gag-Pol ratios, changing the ratio from 20:1 to 20:21 progressively reduced virion RNA dimer stability. The impact of the Gag/Gag-Pol ratio on virion RNA dimerization was amplified when the Gag-Pol PR(−) expression vector was expressed in virion-producing cells. Virions produced from cells expressing Gag and Gag-Pol PR(−) in a 20:21 ratio contained mainly monomeric RNA. Our observations provide the first direct evidence that, in addition to proteolytic processing, the ratio of Gag/Gag-Pol proteins is also important for RNA dimerization and that stable RNA dimers are not required for encapsidation of genomic RNA in HIV_-1.

A study of voluntary disclosure of listed Chinese firms - a stakeholder perspective

Purpose – The aim of this paper is to investigate stakeholder power changes and their impact on firms' disclosure decisions in the Chinese stock market. Using legitimacy theory and stakeholder theory, the paper identifies newly emerged stakeholder groups for listed Chinese firms during three distinguished periods of the development of the Chinese stock market.

Design/methodology/approach – Panel data analysis was undertaken over a period from 1995-2006 with an aim to examine the influence of stakeholder power changes on voluntary disclosures made by 297 listed firms in their 12 years of annual reports. A voluntary disclosure checklist has been used for hand-collecting data from annual reports.

Findings – The finding shows that different stakeholder groups exert different degrees of influence on firms' decision-making in respect of information disclosure during different stages of the development of the Chinese stock market.

Research limitations/implications – The impact of a stakeholder power changes on corporate disclosure has not been well addressed and how listed Chinese firms respond to these changes is still a significant gap in the Chinese corporate disclosure literature. In this study, the paper uses proxies to represent each stakeholder group, discuss power changes of each group and predict the impact of power changes on firms' voluntary disclosure.

Originality/value – The paper identifies the new content of the “social contract” between listed firms and Chinese society and identifies various stakeholder groups of listed Chinese firms in the context of a new “social contract”. The paper predicts that voluntary corporate disclosure is the result of stakeholder pressures and firms use voluntary disclosure as one of their strategies to manage the firm-stakeholder relationship.

Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

Macrophages in the olfactory neuroepithelium are thought to play major roles in tissue homeostasis and repair. However, little information is available at present about possible heterogeneity of these monocyte-derived cells, their turnover rates, and the role of chemokine receptors in this process. To start addressing these issues, this study used Cx3cr1gfp mice, in which the gene sequence for eGFP was knocked into the CX3CR1 gene locus in the mutant allele. Using neuroepithelial whole-mounts from Cx3cr1gfp/+ mice, we show that eGFP+ cells of monocytic origin are distributed in a loose network throughout this tissue and can be subdivided further into two immunophenotypically distinct subsets based on MHC-II glycoprotein expression. BM chimeric mice were created using Cx3cr1gfp/+ donors to investigate turnover of macrophages (and other monocyte-derived cells) in the olfactory neuroepithelium. Our data indicate that the monocyte-derived cell population in the olfactory neuroepithelium is actively replenished by circulating monocytes and under the experimental conditions, completely turned over within 6 months. Transplantation of Cx3cr1gfp/gfp (i.e., CX3CR1-deficient) BM partially impaired the replenishment process and resulted in an overall decline of the total monocyte-derived cell number in the olfactory epithelium. Interestingly, replenishment of the CD68lowMHC-II+ subset appeared minimally affected by CX3CR1 deficiency. Taken together, the established baseline data about heterogeneity of monocyte-derived cells, their replenishment rates, and the role of CX3CR1 provide a solid basis to further examine the importance of different monocyte subsets for neuroregeneration at this unique frontier with the external environment.

Voluntary demand for auditing by farm businesses: an Australian perspective

 This study investigates voluntary demand for auditing by Australian farm businesses, a significant but relatively unexplored segment of the economy. Most farms operate as family partnerships or sole proprietors and we thus focus on incentives to audit arising from internal sources (owner-manager), controlling for traditional incentives arising from external contractual constraints (i.e., debt), organisational characteristics (i.e., size), and agency conflict. We hypothesise that an external audit assists management in enhancing internal control by complementing the process of profit planning and control (budgeting) and that increased family conflict provides an incentive to engage external audit. Of the 457 survey questionnaire respondents, 27% voluntarily engage an external auditor and 66% conduct some formal written planning. Results from logistic regression analyses support the predicted impact of both size and debt on audit, and further support the hypothesised impact of budgeting. The positive association between budgeting and audit confirms the complementary relationship. More importantly, this relationship is not confounded by the combined impact of size and budgeting and debt and budgeting on voluntary audit. In addition, family conflict has no impact on voluntary demand for auditing by farm business.

Finding a place for personal growth in an Australian community singing group for older people

As in many countries, Australia is faced with an aging population. This creates challenges for the maintenance of well-being which can be enhanced by active engagement in society. Music engagement encompasses a range of social participation and has the potential to recognise the contribution of older people to their local communities. Engagement in music by older people (50+) is positively related to individual and community well-being.  Music participation can contribute to a better quality of life, particularly in relation to health and happiness. The possible forms of music engagement are myriad.

This paper focuses on two members of a mixed voluntary singing group formed by older residents of an outer suburban community in Melbourne, Australia.  This study frames music as a positive way for older people to find a place for personal growth and fulfilment in a singing group. This phenomenological qualitative single case study focuses on two members of a small singing ensemble, the Skylarkers, formed to perform at retirement villages, nursing homes and facilities for senior citizens. In this study, data were gathered by interviews and analysed using interpretative phenomenological analysis.

Two significant themes emerged. The first concerned the nature of the choir and its fluid membership and notions of self-identity. The second theme concerns the validation offered to individual members by active music participation through which they gained a sense of purpose, fulfilment and personal growth. This emphasis is unusual in discussions of community music engagement that ordinarily identify the importance of social connections. Groups such as the Skylarkers provide a place for members to continue their active engagement with music performance and music learning.

Maintenance of cultural identity

The aim of this qualitative study is to explore the transmission of health beliefs among three generations of Greek families in Melbourne, Australia and the way they understand both health and disease as an aspect of cultural maintenance in the context of the larger Australian society. More specifically this paper will discuss the extent to which the immigrant generation has created a memory culture and how this has affected the sense of cultural identity of the first and second generation Greek Australians. Unlike the mainstream Australian community, the Greek population has so far maintaned a traditional framework due to the importance they ascribe to both culture and traditions that have been handed down from from the immigrant generation to the first and second generation Greek Australians. However, it is not only the immigrant generation that holds on to these traditions. More and more the first and second generation Greek Australians are set on maintaining their Hellenic heritage, and many community organizations in Melbourne, Australia are now largely supported by the younger generations. The results of this study have practical applications in elucidating how the memory culture that has been created by the immigrant generation may impact this cultural group’s conceptualization of health and the potential this may have to impact the use of health care by providin insight into the role of culture in forming individual or group conceptulizations of health in this community.

Are voluntary wheel running and open-field behavior correlated in mice? Different answers from comparative and artificial selection approaches

Voluntary wheel running and open-field behavior are probably the two most widely used measures of locomotion in laboratory rodents. We tested whether these two behaviors are correlated in mice using two approaches: the phylogenetic comparative method using inbred strains of mice and an ongoing artificial selection experiment on voluntary wheel running. After taking into account the measurement error and phylogenetic relationships among inbred strains, we obtained a significant positive correlation between distance run on wheels and distance moved in the open-field for both sexes. Thigmotaxis was negatively correlated with distance run on wheels in females but not in males. By contrast, mice from four replicate lines bred for high wheel running did not differ in either distance covered or thigmotaxis in the open field as compared with mice from four non-selected control lines. Overall, results obtained in the selection experiment were generally opposite to those observed among inbred strains. Possible reasons for this discrepancy are discussed.

Attrition and maintenance of the Berber language in Tunisia

In this article, I examine the situation of Tunisian Berber from a linguistic and sociolinguistic perspective. The prolonged institutional marginalization of this language, the lack to date of a comprehensive documentation, and the passive attitude of the speakers themselves are contributing factors to its current decline. Present predictions as to its immediate extinction are alarming. However, conclusions drawn in other studies are not adequately supported and evidence from data recently collected in southern Tunisia partially refutes the claim that the decline of Tunisian Berber is irreversible. Even though attrition is evident in borrowing en masse from Arabic, grammatical evidence shows little structural change. After many years of neglect, efforts to document fully the remaining vernaculars are a positive step towards the revival of this variety of Berber. In this article I have three goals. First, to give an assessment of the problems and the challenges facing Tunisian Berber. Second, to describe the extent of attrition of this language based on field-collected data and, third, to suggest some directions for future studies of Tunisian Berber and strategies to stimulate its revival. Complete oral narratives, the first to be published, will be appended to the text in order to allow the linguistic community access to materials in its language.