Heme Mediated STAT3 Activation in Severe Malaria

The mortality of severe malaria [cerebral malaria (CM), severe malaria anemia (SMA), acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)] remains high despite the availability associated with adequate treatments. Recent studies in our laboratory and others have revealed a hitherto unknown correlation between chemokine CXCL10/CXCR3, Heme/HO-1 and STAT3 and cerebral malaria severity and mortality. Although Heme/HO-1 and CXCL10/CXCR3 interactions are directly involved in the pathogenesis of CM and fatal disease, the mechanism dictating how Heme/HO-1 and CXCL10/CXCR3 are expressed and regulated under these conditions is still unknown. We therefore tested the hypothesis that these factors share common signaling pathways and may be mutually regulated.We first clarified the roles of Heme/HO-1, CXCL10/CXCR3 and STAT3 in CM pathogenesis utilizing a well established experimental cerebral malaria mouse (ECM, P. berghei ANKA) model. Then, we further determined the mechanisms how STAT3 regulates HO-1 and CXCL10 as well as mutual regulation among them in CRL-2581, a murine endothelial cell line.The results demonstrate that (1) STAT3 is activated by P. berghei ANKA (PBA) infection in vivo and Heme in vitro. (2) Heme up-regulates HO-1 and CXCL10 production through STAT3 pathway, and regulates CXCL10 at the transcriptional level in vitro. (3) HO-1 transcription is positively regulated by CXCL10. (4) HO-1 regulates STAT3 signaling.Our data indicate that Heme/HO-1, CXCL10/CXCR3 and STAT3 molecules as well as related signaling pathways play very important roles in the pathogenesis of severe malaria. We conclude that these factors are mutually regulated and provide new opportunities to develop potential novel therapeutic targets that could be used to supplement traditional prophylactics and treatments for malaria and improve clinical outcomes while reducing malaria mortality. Our ultimate goal is to develop novel therapies targeting Heme or CXCL10-related biological signaling molecules associated with development of fatal malaria

Health risk behaviours among adolescents in the English-speaking Caribbean: a review

<p>Abstract</p> <p>Background</p> <p>The aim of this paper was to review and summarize research on prevalence of health risk behaviours, their outcomes as well as risk and protective factors among adolescents in the English-speaking Caribbean.</p> <p>Methods</p> <p>Searching of online databases and the World Wide Web as well as hand searching of the <it>West Indian Medical Journal </it>were conducted. Papers on research done on adolescents aged 10 – 19 years old and published during the period 1980 – 2005 were included.</p> <p>Results</p> <p>Ninety-five relevant papers were located. Five papers were published in the 1980s, 47 in the 1990s, and from 2000–2005, 43 papers. Health risk behaviours and outcomes were divided into seven themes. Prevalence data obtained for these, included lifetime prevalence of <b>substance use</b>: cigarettes-24% and marijuana-17%; <b>high risk sexual behaviour</b>: initiation of sexual activity ≤ 10 years old-19% and those having more than six partners-19%; <b>teenage pregnancy</b>: teens account for 15–20% of all pregnancies and one-fifth of these teens were in their second pregnancy; <b>Sexually-Transmitted Infections (STIs)</b>: population prevalence of gonorrhoea and/or chlamydia in 18–21 year-olds was 26%; <b>mental health</b>: severe depression in the adolescent age group was 9%, and attempted suicide-12%; <b>violence and juvenile delinquency</b>: carrying a weapon to school in the last 30 days-10% and almost always wanting to kill or injure someone-5%; <b>eating disorders and obesity</b>: overweight-11%, and obesity-7%. Many of the risk behaviours in adolescents were shown to be related to the adolescent's family of origin, home environment and parent-child relationships. Also, the protective effects of family and school connectedness as well as increased religiosity noted in studies from the United States were also applicable in the Caribbean.</p> <p>Conclusion</p> <p>There is a substantial body of literature on Caribbean adolescents documenting prevalence and correlates of health risk behaviours. Future research should emphasize the designing and testing of interventions to alleviate this burden.</p

The new covenant of employability

Purpose – Changing career patterns and the erosion of job security have led to a growing emphasis on employability as a basis for career and employment success. The written and psychological contracts between employer and employer have become more transactional and less relational, and loyalty is no longer a guarantee of ongoing employment. Individuals are thus expected to take primary responsibility for their own employability rather than relying on the organisation to direct and maintain their careers. The purpose of this paper is to identify and examine the assumptions underpinning the concept of employability and evaluate the extent to which employability has been adopted as a new covenant in the employment relationship. Design/methodology/approach – Through a review of relevant literature the paper discusses current research on careers and employability and examines the available evidence regarding its adoption as a basis for contemporary employment relationships. Findings – The paper finds that the transfer of responsibility for employability from organisation to individual has not been widespread. There is still an expectation that organisations will manage careers through job-specific training and development. Employability has primarily benefitedemployees with highly developed or high-demand skills. Employability is not a guarantee of finding suitable employment. Practical implications – Employers can assist their employees by clarifying changes to the psychological contract, highlighting the benefits of career self-management, and providing training and development in generic employability skills. Originality/value – The paper questions underlying assumptions about employability and explores issues of relevance to human resource managers, policy-makers, employers and employees.Marilyn Clarke and Margaret Patrickso

Human resource management in Australia

Marilyn Clark and Margaret Patrickso

Implementation of evidence-based healthcare in Papua New Guinea

AIM: The aim of this research was to understand how health workers in developing countries reach diagnostic and treatment decisions. In developing countries, health workers are often forced to make diagnostic and treatment decisions based on limited knowledge, unhelpful information, infrequent and low technology back-up services and without the support of more senior staff. Yet patients continue to be treated. This paper investigates how primary healthcare workers in such contexts reach these diagnostic and treatment decisions. METHOD: Using a qualitative methodology, 58 primary healthcare workers from the three primary healthcare facilities in Papua New Guinea – aid posts, sub-health centres and health centres – participated in an in-depth interview, in order to investigate how diagnostic and treatment decisions were made. RESULTS:  Although participants were originally trained in the biomedical model, they lived and worked in a context where other belief systems operated to diagnose and treat illness. This led to the coexistence of at least three models of treatment: the biomedical model, traditional indigenous health practices and Christian beliefs. Thus, a homogenous biomedical understanding of health and well-being was not possible in this setting, and treatment options did not always follow the biomedical recommendations. CONCLUSIONS: In developing countries where competing medical frame works exist, evidence-based practices may be more difficult to implement. Although the skill and knowledge of the provider and availability of treatment resources are still important, belief in the accuracy of the diagnosis and the potency of the treatment by the patient and the patient's community as well as the health provider may be just as significant.Carol Patricia Davy and Margaret Patrickso

Multi-user interactive drama : the macro view - three structural layers

Narrative is generally crafted around a Three Act structure that dates back to Aristotle's Poetics. This paper asks to what extent the beginning, middle and end of a linear story remain relevant in interactive environments where drama can result as much from the interplay of rules and multi user participation. In this context drama appears to build through short, yet ongoing cycles of variable engagement. This allows for an alternative, structural approach to the application of Aristotle's Poetics in multi-user interactive environments involving three component layers, rather than three linear acts: The Source Drama, The User Drama and The Multi Drama.5 page(s