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    Comparing rates of mycobacterial clearance in sputum smear-negative and smear-positive adults living with HIV
    (BMC (part of Springer Nature), 2021-05-22) Machowski, Edith E.; Letutu, Matebogo; Lebina, Limakatso; Waja, Ziyaad; Msandiwa, Reginah; Milovanovic, Minja; Gordhan, Bhavna G.; Otwombe, Kennedy; Friedrich, Sven O.; Chaisson, Richard; Diacon, Andreas H.; Kana, Bavesh; Martinson, Neil
    Background: Pulmonary tuberculosis (TB) in people living with HIV (PLH) frequently presents as sputum smearnegative. However, clinical trials of TB in adults often use smear-positive individuals to ensure measurable bacterial responses following initiation of treatment, thereby excluding HIV-infected patients from trials. Methods: In this prospective case cohort study, 118 HIV-seropositive TB patients were assessed prior to initiation of standard four-drug TB therapy and at several time points through 35 days. Sputum bacillary load, as a marker of treatment response, was determined serially by: smear microscopy, Xpert MTB/RIF, liquid culture, and colony counts on agar medium. Results: By all four measures, patients who were baseline smear-positive had higher bacterial loads than those presenting as smear-negative, until day 35. However, most smear-negative PLH had significant bacillary load at enrolment and their mycobacteria were cleared more rapidly than smear-positive patients. Smear-negative patients’ decline in bacillary load, determined by colony counts, was linear to day 7 suggesting measurable bactericidal activity. Moreover, the decrease in bacterial counts was comparable to smear-positive individuals. Increasing cycle threshold values (Ct) on the Xpert assay in smear-positive patients to day 14 implied decreasing bacterial load. Conclusion: Our data suggest that smear-negative PLH can be included in clinical trials of novel treatment regimens as they contain sufficient viable bacteria, but allowances for late exclusions would have to be made in sample size estimations. We also show that increases in Ct in smear-positive patients to day 14 reflect treatment responses and the Xpert MTB/RIF assay could be used as biomarker for early treatment response.
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    Integrated knowledge translation to advance noncommunicable disease policy and practice in South Africa : application of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework
    (BioMed Central, 2021-05-17) Jessani, Nasreen S.; Rohwer, Anke; Schmidt, Bey-Marrie; Delobelle, Peter
    Background: In response to the “know–do” gap, several initiatives have been implemented to enhance evidenceinformed decision-making (EIDM). These include individual training, organizational culture change management, and legislative changes. The importance of relationships and stakeholder engagement in EIDM has led to an evolution of models and approaches including integrated knowledge translation (IKT). IKT has emerged as a key strategy for ensuring that engagement is equitable, demand-driven, and responsive. As a result, the African-German Collaboration for Evidence-Based Healthcare and Public Health in Africa (CEBHA+) incorporated an IKT approach to influence noncommunicable diseases (NCD) policy and practice. We documented the phased process of developing, implementing, and monitoring the IKT approach in South Africa; and explored the appropriateness of using the exploration, preparation, implementation, and sustainment (EPIS) framework for this purpose. Methods: We mapped the South Africa IKT approach onto the EPIS framework using a framework analysis approach. Notes of team meetings, stakeholder matrices, and engagement strategies were analysed and purposefully plotted against the four phases of the framework in order to populate the different constructs. We discussed and finalized the analysis in a series of online iterations until consensus was reached. Results: The mapping exercise revealed an IKT approach that was much more iterative, dynamic, and engaging than initially thought. Several constructs (phase-agnostic) remained important and stable across EPIS phases: stable and supportive funding; committed and competent leadership; skilled and dedicated IKT champions; diverse and established personal networks; a conducive and enabling policy environment; and boundary-spanning intermediaries. Constructs such as “innovations” constantly evolved and adapted to the changing inner and outer contexts (phase-specific). Conclusions: Using the EPIS framework to interrogate, reflect on, and document our IKT experiences proved extremely relevant and useful. Phase-agnostic constructs proved critical to ensure resilience and agility of NCD deliberations and policies in the face of highly dynamic and changing local contexts, particularly in view of the current coronavirus disease 2019 (COVID-19) pandemic. Bridging IKT with a framework from implementation science helps to reflect on this process and can guide the development and planning of similar interventions and strategies.
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    Systematic review and narrative synthesis of suicide prevention in high-schools and universities : a research agenda for evidence-based practice
    (BMC (part of Springer Nature), 2021-06-10) Breet, Elsie; Matooane, Matsie; Tomlinson, Mark; Bantjes, Jason
    Background: Youth suicide prevention in high-schools and universities is a public health priority. Our aim was to propose a research agenda to advance evidence-based suicide prevention in high-schools and universities by synthesizing and critically reviewing the research focus and methodologies used in existing intervention studies. Methods: Fourteen databases were systematically searched to identify studies which evaluate suicide prevention interventions delivered on high-school or university campuses, with before and after measures. Data from included studies (n = 43) were extracted to identify what, where, how and for whom interventions have been tested. Narrative synthesis was used to critically evaluate research focus and methodology. Study quality was assessed. Results: Research has focused primarily on selective interventions, with less attention on indicated and universal interventions. Most evidence comes from North America and high-income countries. The target of interventions has been: non-fatal suicidal behaviour; confidence and ability of staff/students to intervene in a suicidal crisis; suicide-related knowledge and attitudes; and suicide-related stigma. No studies included suicide deaths as an outcome, evaluated eco-systemic interventions, explored how context influences implementation, used multisite study designs, or focused explicitly on LGBTQ+ youth. Two studies evaluated digital interventions. Quality of the majority of studies was compromised by lack of methodological rigour, small samples, and moderate/high risk of bias. Interventions often assume the existence of an external well-functioning referral pathway, which may not be true in low-resource settings. Conclusion: To advance evidence-based suicide prevention in educational settings we need to: conduct more high-quality clinical and pragmatic trials; promote research in low- and middle-income countries; test targeted interventions for vulnerable populations (like LGBTQ+ youth), evaluate interventions where death by suicide is the primary outcome; include translational studies and use implementation science to promote intervention uptake; evaluate the potential use of digital and eco-systemic interventions; and conduct multisite studies in diverse cultural settings.
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    Effects of long-term (42 years) tillage sequence on soil chemical characteristics in a dryland farming system
    (Elsevier, 2021) Tshuma, Flackson; Rayns, Francis; Labuschagne, Johan; Bennett, James; Swanepoel, Pieter Andreas
    No-tillage can improve soil quality but can also increase the stratification of soil chemical parameters. Nutrient uptake by crops might be limited when nutrients are stratified, especially in semi-arid or Mediterranean regions. To reduce stratification, infrequent tillage could be considered. However, there is a paucity of information on the effects of long-term infrequent tillage on the stratification of soil chemical parameters. This study aimed to assess the effects of long-term infrequent tillage on the stratification of selected soil chemical parameters to a depth of 300 mm. The research was conducted on a long-term (42 years) research site at Langgewens Research Farm in South Africa. Seven tillage treatments were investigated: continuous mouldboard ploughing to a depth of 200 mm, tine-tillage to 150 mm, shallow tine-tillage to 75 mm, no-tillage, shallow tine-tillage every second year in rotation with no-tillage, shallow tine-tillage every third year in rotation with no-tillage and shallow tine-tillage every fourth year in rotation with no-tillage. Tillage treatments had differential effects on the distribution of soil chemical parameters. The mouldboard plough prevented stratification of most soil chemical parameters, such as soil acidity, soil organic carbon (SOC), extractable P, exchangeable Ca and Mg and cation exchange capacity (CEC). However, mouldboard ploughing also led to significantly lower SOC stocks and extractable P stocks. The SOC stocks and extractable P stocks of the no-tillage treatment were not significantly different from those of the infrequent tillage treatments. Overall, the infrequent tillage treatments were no better (P > 0.05) than the no-tillage treatment as infrequent tillage could not effectively ameliorate the stratification of most soil chemical parameters and did not increase the stocks and stratification ratios of SOC and extractable P.
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    Microbial function and genital inflammation in young South African women at high risk of HIV infection
    (BMC (part of Springer Nature), 2020-11-21) Alisoltani, Arghavan; Manhanzva, Monalisa T.; Potgieter, Matthys; Balle, Christina; Bell, Liam; Ross, Elizabeth; Iranzadeh, Arash; du Plessis, Michelle; Radzey, Nina; McDonald, Zac; Calder, Bridget; Allali, Imane; Mulder, Nicola; Dabee, Smritee; Barnabas, Shaun; Gamieldien, Hoyam; Godzik, Adam; Blackburn, Jonathan M.; Tabb, David L.; Bekker, Linda-Gail; Jaspan, Heather B.; Passmore, Jo-Ann S.; Masson, Lindi
    Background: Female genital tract (FGT) inflammation is an important risk factor for HIV acquisition. The FGT microbiome is closely associated with inflammatory profile; however, the relative importance of microbial activities has not been established. Since proteins are key elements representing actual microbial functions, this study utilized metaproteomics to evaluate the relationship between FGT microbial function and inflammation in 113 young and adolescent South African women at high risk of HIV infection. Women were grouped as having low, medium, or high FGT inflammation by K-means clustering according to pro-inflammatory cytokine concentrations. Results: A total of 3186 microbial and human proteins were identified in lateral vaginal wall swabs using liquid chromatography-tandem mass spectrometry, while 94 microbial taxa were included in the taxonomic analysis. Both metaproteomics and 16S rRNA gene sequencing analyses showed increased non-optimal bacteria and decreased lactobacilli in women with FGT inflammatory profiles. However, differences in the predicted relative abundance of most bacteria were observed between 16S rRNA gene sequencing and metaproteomics analyses. Bacterial protein functional annotations (gene ontology) predicted inflammatory cytokine profiles more accurately than bacterial relative abundance determined by 16S rRNA gene sequence analysis, as well as functional predictions based on 16S rRNA gene sequence data (p < 0.0001). The majority of microbial biological processes were underrepresented in women with high inflammation compared to those with low inflammation, including a Lactobacillus-associated signature of reduced cell wall organization and peptidoglycan biosynthesis. This signature remained associated with high FGT inflammation in a subset of 74 women 9 weeks later, was upheld after adjusting for Lactobacillus relative abundance, and was associated with in vitro inflammatory cytokine responses to Lactobacillus isolates from the same women. Reduced cell wall organization and peptidoglycan biosynthesis were also associated with high FGT inflammation in an independent sample of ten women. Conclusions: Both the presence of specific microbial taxa in the FGT and their properties and activities are critical determinants of FGT inflammation. Our findings support those of previous studies suggesting that peptidoglycan is directly immunosuppressive, and identify a possible avenue for biotherapeutic development to reduce inflammation in the FGT.