Glutathione and growth inhibition of Mycobacterium tuberculosis in healthy and HIV infected subjects

Intracellular levels of glutathione are depleted in patients with acquired immunodeficiency syndrome in whom the risk of tuberculosis, particularly disseminated disease is many times that of healthy individuals. In this study, we examined the role of glutathione in immunity against tuberculosis infection in samples derived from healthy and human immunodeficiency virus infected subjects. Our studies confirm that glutathione levels are reduced in peripheral blood mononuclear cells and in red blood cells isolated from human immunodeficiency virus-infected subjects (CD4>400/cumm). Furthermore, treatment of blood cultures from human immunodeficiency virus infected subjects with N-acetyl cysteine, a glutathione precursor, caused improved control of intracellular M. tuberculosis infection. N-acetyl cysteine treatment decreased the levels of IL-1, TNF-α, and IL-6, and increased the levels of IFN-γ in blood cultures derived from human immunodeficiency virus-infected subjects, promoting the host immune responses to contain M. tuberculosis infection successfully

The multilingual university: language ideology, hidden policies and language practices in Malawian universities

Globalisation is increasingly affecting universities worldwide. In African contexts, language policies exhibit an inheritance situation in which countries continue to implement policies which favour colonial languages in education. This paper investigates the Malawian higher education context and the ways in which staff engage with multilingualism. It examines the implementation of language policies by staff in their classrooms and explores the attitudes of staff members towards the current monolingual language policy and practices in higher education in the country. The paper draws on a 4-month ethnography carried out in eight Malawian universities. Findings indicate that the language ‘rules’ imposed by staff are highly variable and that diverse language ‘policies’ are implemented and enforced by staff, some of whom operate strictly monolingual approaches while others adopt multilingual approaches. Staff display a range of attitudes towards multilingualism, influenced by competing pressures of ensuring students comprehend the subject matter while also seeking to improve their English skills against the broader backdrop of language practices and expectations in the country

The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes

Context: Obesity-associated inflammation is a contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM); the mechanisms underlying the progression to T2DM are unclear. The adipokine resistin has demonstrated pro-inflammatory properties in relation to obesity and T2DM. Objective: To characterize resistin expression in human obesity and address the role of resistin in the innate immune pathway. Furthermore, examine the influence of lipopolysaccharide, recombinant human resistin (rhResistin), insulin and rosiglitazone in human adipocytes. Finally, analyze the effect of rhResistin on the expression of components of the NF-κB pathway and insulin signaling cascade. Methods: Abdominal subcutaneous adipose tissue was obtained from patients undergoing elective liposuction surgery (n = 35, aged: 36-49 yr; BMI: 26.5 ± 5.9 kg/m2). Isolated adipocytes were cultured with rhResistin (10-50 ng/ml). The level of cytokine secretion from isolated adipocytes was examined by ELISA. The effect of rhResistin on protein expression of components of the innate immune pathway was examined by Western blot. Results: In-vitro studies demonstrated that antigenic stimuli increase resistin secretion (P < 0.001) from isolated adipocytes. Pro-inflammatory cytokine levels were increased in response to rhResistin (P < 0.001); this was attenuated by rosiglitazone (P < 0.01). When examining components of the innate immune pathway, rhResistin stimulated Toll-like receptor-2 protein expression. Similarly, mediators of the insulin signaling pathway, phosphospecific JNK1 and JNK2, were upregulated in response to rhResistin. Conclusion: Resistin may participate in more than one mechanism to influence pro-inflammatory cytokine release from human adipocytes; potentially via the integration of NF-κB and JNK signaling pathways

‘Languages don’t have bones, so you can just break them’: rethinking multilingualism in education policy and practice in Africa

Multilingualism is widespread amongst individuals and communities in African countries. However, language-in-education policies across the continent continue to privilege monolingual approaches to language use in the classroom. In this paper we highlight the colonial origins of these monolingual ideologies and discuss the detrimental effects which arise when learners’ linguistic repertoires are not welcomed within the education system. We draw attention to major themes within education across a range of contexts: policy vagueness, teachers as policy implementers, and the creation and imposition of boundaries. We advocate for a language-in-education approach which brings the outside in, which welcomes individuals’ lived multilingual realities and which values these as resources for learning. We highlight the ways in which translanguaging could represent a positive shift to the way in which multilingual language practices are talked about, and can contribute to decolonising language policy in African contexts. We conclude by calling to action those working on education and policy to ensure that learners and teachers are better supported. We call ultimately for a rethinking of multilingualism

Glycerol monolaurate prevents mucosal SIV transmission

Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection1, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission2–4. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)–rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry5,6. Here we show in this SIV–macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α (also known as CCL20), plasmacytoid dendritic cells and CCR5+ cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4+ T cells to fuel this obligate expansion. We then show that glycerol monolaurate—a widely used antimicrobial compound7with inhibitory activity against the production of MIP-3α and other proinflammatory cytokines8—can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to blockHIV-1 mucosal transmission

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Hearing loss in the pediatric patient

Objective To provide recommendations for the workup of hearing loss in the pediatric patient. Methods Expert opinion by the members of the International Pediatric Otolaryngology Group. Results Consensus recommendations include initial screening and diagnosis as well as the workup of sensorineural, conductive and mixed hearing loss in children. The consensus statement discusses the role of genetic testing and imaging and provides algorithms to guide the workup of children with hearing loss. Conclusion The workup of children with hearing loss can be guided by the recommendations provided herein

Emerging principles for researching multilingually in linguistic ethnography: Reflections from Botswana, Tanzania, the UK, and Zambia

This paper discusses collaborative ethnographic work investigating multilingualism within education in Botswana, Tanzania, and Zambia. The paper takes a reflective perspective on how research is conducted and the role that multilingualism and collaboration can play in the research process itself. As a team of thirteen individuals, working across four countries, we bring a range of multilingual repertoires to the project. In this paper we discuss three principles which have been important in guiding our thinking and practice. These are: researching multilingually; researching collaboratively; and researching responsively. We discuss the rationale behind these principles and the role they play in our work. We then discuss challenges and successes which have emerged from implementing these principles in practice and use these to outline a framework that those interested in conducting similar work can use to guide their own thinking and practices. The data discussed in this article consist of a corpus of vignettes from members of the project team. Ten vignettes have been collaboratively analysed adopting a thematic analysis. Tasked with reflecting on, and evaluating, the principles the vignette data provide insight into the opportunities and challenges of working multilingually, collaboratively, and responsively within a team with diverse linguistic repertoires

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART