The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice

Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals

Inviting backchat: how schools and communities in Ghana, Swaziland and Kenya support children to contextualize knowledge and create agency through sexuality education

Education about sex, relationships and HIV and AIDS in African contexts is riddled with socio-cultural complexity. In this paper the authors argue that in extreme contexts education can lead change further by developing young people as significant actors in their own lives and in the lives of the community by bringing bring about change in attitudes in the community, as well as practices in schools. A qualitative study was undertaken in eight primary schools of the use of student knowledge and voice to change attitudes, impact upon socio cultural beliefs, adult-child dialogue and drive changes in practice in AIDS education. Drawing on a contextual framework that includes a socio-cultural approach to education, Basil Bernstein’s well established theories of everyday and school knowledge and Catherine Campbell’s notion of AIDS competent communities, it shows how this initiative variably unfolded in six sub-Saharan countries (Botswana, Ghana, Kenya, South Africa, Swaziland and Tanzania, – although only the latter three are discussed in detail) and analyses the potential of schools to operate for the benefit of children in difficult circumstances, especially with regard to poverty, gender, sexual violence and health. Participation, dialogue and agency were the key factors

Blood, sex and trust: : The limits of the population-based risk management paradigm

Blood screening is imperfect so Donor Health Check questionnaires (DHC) are used to defer those whose ‘behaviour’ suggests disproportionate risk of Blood Borne Infection (BBI). Taking the UK case, we compare deferment of three sub-populations with different HIV prevalence; Men-who-have-Sex-with-Men (4.7%), black-Africans (3.7%) and ‘the-general-(heterosexual)-population’ (c.0.09%) arguing that, with respect to STIs, DHC assesses risk based on broad population-level risk-groups not behaviour. This approach relies on an imaginative geography that distances heterosexual risk from the domestic population. Most DHCs knowingly commit the ecological fallacy allowing population-level statistics to obscure within-group diversity, inadequately identifying the risk posed by ‘low-risk-groups’. The disjuncture between ontological risk phenomenon (diverse sexual practice) and the epistemological grid used to map risk (homogenised risk-groups) needs examination. Unpacking the category ‘heterosexual’ would both better differentiate risk within this group and change the relative-risk calculated for ‘high-risk groups’. We call for piloting of practice-based questions and a mixed-method approach to DHCs to more accurately assess all potential donors.PostprintPeer reviewe

The efficiency and effectiveness of utilizing diagrams in interviews: an assessment of participatory diagramming and graphic elicitation

Abstract Background This paper focuses on measuring the efficiency and effectiveness of two diagramming methods employed in key informant interviews with clinicians and health care administrators. The two methods are 'participatory diagramming', where the respondent creates a diagram that assists in their communication of answers, and 'graphic elicitation', where a researcher-prepared diagram is used to stimulate data collection. Methods These two diagramming methods were applied in key informant interviews and their value in efficiently and effectively gathering data was assessed based on quantitative measures and qualitative observations. Results Assessment of the two diagramming methods suggests that participatory diagramming is an efficient method for collecting data in graphic form, but may not generate the depth of verbal response that many qualitative researchers seek. In contrast, graphic elicitation was more intuitive, better understood and preferred by most respondents, and often provided more contemplative verbal responses, however this was achieved at the expense of more interview time. Conclusion Diagramming methods are important for eliciting interview data that are often difficult to obtain through traditional verbal exchanges. Subject to the methodological limitations of the study, our findings suggest that while participatory diagramming and graphic elicitation have specific strengths and weaknesses, their combined use can provide complementary information that would not likely occur with the application of only one diagramming method. The methodological insights gained by examining the efficiency and effectiveness of these diagramming methods in our study should be helpful to other researchers considering their incorporation into qualitative research designs

Effects of HIV/TAT protein expression and chronic selegiline treatment on spatial memory, reversal learning and neurotransmitter levels in mice

Neurotoxic viral protein TAT may contribute to deficits in dopaminergic and cognitive function in individuals infected with human immunodeficiency virus. Transgenic mice with brain-specific doxycycline-induced TAT expression (TAT+, TAT- control) show impaired cognition. However, previously reported TAT-induced deficits in reversal learning may be compromised by initial learning deficits. We investigated the effects of TAT expression on memory retention/recall and reversal learning, and neurotransmitter function. We also investigated if TAT-induced effects can be reversed by improving dopamine function with selegiline, a monoamine oxidase inhibitor. Mice were tested in the Barnes maze and TAT expression was induced after the task acquisition. Selegiline treatment continued throughout behavioral testing. Dopamine, serotonin and glutamate tissue levels in the prefrontal/orbitofrontal cortex, hippocampus and caudate putamen were measured using high performance liquid chromatography. Neither TAT expression nor selegiline altered memory retention. On day 2 of reversal learning testing, TAT+ mice made fewer errors and used more efficient search strategies than TAT- mice. TAT expression decreased dopamine turnover in the caudate putamen, increased serotonin turnover in the hippocampus and tended to increase the conversion of glutamate to glutamine in all regions. Selegiline decreased dopamine and serotonin metabolism in all regions and increased glutamate levels in the caudate putamen. In the absence of impaired learning, TAT expression does not impair spatial memory retention/recall, and actually facilitates reversal learning. Selegiline-induced increases in dopamine metabolism did not affect cognitive function. These findings suggest that TAT-induced alterations in glutamate signaling, but not alterations in monoamine metabolism, may underlie the facilitation of reversal learning

Determining the performance of a Diffuser Augmented Wind Turbine using a combined CFD/BEM method

Traditionally, the optimisation of a Diffuser Augmented Wind Turbine has focused on maximising power output. However, due to the often less than ideal location of small-scale turbines, cut-in speed and starting time are of equal importance in maximising Annual Energy Production, which is the ultimate goal of any wind turbine design. This paper proposes a method of determining power output, cut-in speed and starting time using a combination of Computational Fluid Dynamics and Blade Element Momentum theory. The proposed method has been validated against published experimental data

The appropriateness of empirical antibiotic therapy in the management of symptomatic urinary tract infection patients—a cross-sectional study in Nairobi County, Kenya

Funding: Global Challenges Research Fund (GCRF PhD scholarship).Background: In low- and middle-income countries, symptomatic urinary tract infection (UTI) patients are often prescribed antibiotics without microbiological confirmation. UTIs caused by antibiotic-resistant bacteria are increasingly common, and this heightens the risk of empirical treatment failure. This study evaluates the appropriateness of empirical antibiotic therapy to UTI patients in Nairobi County, Kenya. Methods: A hospital-based, cross-sectional study was conducted in Nairobi County, Kenya, amongst symptomatic adult and child patients. UTI was defined as a monoculture growth with colony counts of ≥104 cfu/mL. Antimicrobial susceptibility testing was performed by the Kirby–Bauer disc diffusion method. Empirical therapy was considered appropriate if the pathogen isolated was susceptible to the prescribed antibiotic and inappropriate if the pathogen was resistant to the prescribed antibiotic. Results: A total of 552 participants were enrolled with a median age of 29 years (interquartile range: 24–36). The majority were female, 398 (72%). Of the 552, 274 (50%) received empirical antibiotic therapy, and 95/274 (35%) were confirmed to have UTI by culture. The antibiotics most frequently prescribed were fluoroquinolones [ciprofloxacin in 80 (30%) and levofloxacin 43 (16%)], amoxicillin–clavulanic acid in 48 (18%) and nitrofurantoin in 32 (12%). Amongst the 95 patients with bacteriological confirmation of UTI, 50 (53%) received appropriate empirical antibiotic therapy, whilst for 38 (40%) participants, the therapy was inappropriate. Conclusions: The complexity of appropriate empirical treatment for UTIs is compounded by high levels of resistance in UTI pathogens. Antimicrobial resistance surveillance strategies that could help in designing appropriate empirical regimens in resource constrained settings should be adopted for optimal empiric therapy.Peer reviewe

Adult vitamin D deficiency leads to behavioural and brain neurochemical alterations in C57BL/6J and BALB/c mice

Epidemiological evidence suggests that low levels of vitamin D may predispose people to develop depression and cognitive impairment. While rodent studies have demonstrated that prenatal vitamin D deficiency is associated with altered brain development, there is a lack of research examining adult vitamin D (AVD) deficiency. The aim of this study was to examine the impact of AVD deficiency on behaviour and brain function in the mouse. Ten-week old male C57BL/6J and BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We assessed a broad range of behavioural domains, excitatory and inhibitory neurotransmission in brain tissue, and, in separate groups of mice, locomotor response to d-amphetamine and MK-801. Overall, AVD deficiency resulted in hyperlocomotion in a novel open field and reduced GAD65/67 levels in brain tissue. AVD-deficient BALB/c mice had altered behaviour on the elevated plus maze, altered responses to heat, sound and shock, and decreased levels of glutamate and glutamine, and increased levels of GABA and glycine. By contrast C57BL/6J mice had a more subtle phenotype with no further behavioural changes but significant elevations in serine, homovanillic acid and 5-hydroxyindoleacetic acid. Although the behavioural phenotype of AVD did not seem to model a specific disorder, the overall reduction in GAD65/67 levels associated with AVD deficiency may be relevant to a number of neuropsychiatric conditions. This is the first study to show an association between AVD deficiency and prominent changes in behaviour and brain neurochemistry in the mouse