PLoS medicine
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A pathogenic hallmark of rheumatoid arthritis (RA) is persistent inflammatory responses in target tissues and organs. Immune responses mediated by T cells and autoantibodies are known to play pivotal roles. A possible interpretation for this observation is a loss of negative regulation of autoimmune responses. Here we sought to investigate whether B7-H4, a cell surface inhibitory molecule of the B7-CD28 signaling pathway, may play a role in the pathogenesis of RA. ⋯ Our findings in mice indicate that sH4 acts as a decoy molecule to block the inhibitory functions of cell-surface B7-H4, leading to exacerbation of collagen-induced arthritis. If the preliminary correlation between sH4 levels and disease activity in patients with RA can be confirmed to reflect a similar mechanism, these findings suggest a novel target for treatment approaches. Please see later in the article for the Editors' Summary.
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There is international interest in enhancing recruitment of minority ethnic people into research, particularly in disease areas with substantial ethnic inequalities. A recent systematic review and meta-analysis found that UK South Asians are at three times increased risk of hospitalisation for asthma when compared to white Europeans. US asthma trials are far more likely to report enrolling minority ethnic people into studies than those conducted in Europe. We investigated approaches to bolster recruitment of South Asians into UK asthma studies through qualitative research with US and UK researchers, and UK community leaders. ⋯ Most researchers and community leaders view the broadening of participation in research as important and are reasonably optimistic about the feasibility of recruiting South Asians into asthma studies provided that the barriers can be overcome. Suggested strategies for improving recruitment in the UK included a considerably improved support structure to provide academics with essential contextual information (e.g., languages of particular importance and contact with local gatekeepers), and the need to ensure that care is taken to engage with the minority ethnic communities in ways that are both culturally appropriate and sustainable; ensuring reciprocal benefits was seen as one key way of avoiding gatekeeper fatigue. Although voluntary measures to encourage researchers may have some impact, greater impact might be achieved if UK funding bodies followed the lead of the US National Institutes of Health requiring recruitment of ethnic minorities. Such a move is, however, likely in the short- to medium-term, to prove unpopular with many UK academics because of the added "hassle" factor in engaging with more diverse populations than many have hitherto been accustomed to.
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In the fourth in a series of six articles on packages of care for mental disorders in low- and middle-income countries, Vivek Benegal and colleagues discuss the treatment of alcohol use disorders.
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In the second in a series of six articles on packages of care for mental health disorders in low- and middle-income countries, Caroline Mbuba and Charles Newton discuss treatment for epilepsy.
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Data from HIV treatment programs in resource-limited settings show extensive rates of loss to follow-up (LTFU) ranging from 5% to 40% within 6 mo of antiretroviral therapy (ART) initiation. Our objective was to project the clinical impact and cost-effectiveness of interventions to prevent LTFU from HIV care in West Africa. ⋯ Interventions that prevent LTFU in resource-limited settings would substantially improve survival and would be cost-effective by international criteria with efficacy of at least 12%-41%, depending on the cost of intervention, based on a reported 18% cumulative incidence of LTFU at 1 y after ART initiation. The commitment to start ART and treat HIV in these settings should include interventions to prevent LTFU.