Grant Funded: Journal Articles

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https://hdl.handle.net/11288/583121

All papers that are published (or in the process of being published) in a scientific journal by SAMRC staff.

Now showing 1 - 5 of 5

Motivations for Relationships as Sources of Meaning: Ghanaian and South African Experiences
(Frontiers, 2020-08-21) Wissing, M.P.; Fadiji, A.W.; Schutte, L.; Chigeza, S.; Schutte, W.D.; Temane, Q.M.
Afrocentric paradigms reflect assumptions of the overarching importance of interconnectedness and social bonds in meaningful experiences. It is, however, not known if types of relatedness vary in importance as meaning sources in the subjective experiences of laypeople, or what the reasons are that they ascribe to the importance of relationships. The empirical and theoretical substantiation of philosophical assumptions is needed to provide a scientific basis for appropriate well-being interventions in African contexts. Therefore, this study aimed to empirically explore the relative importance of various types of relationships as sources of meaning and in particular why relationships are important to laypeople in relatively collectivist African contexts. Using a bottom-up qualitative approach with quantification of responses, this study explored how prominently relationships featured as meaning sources compared to other domains of life and then, in particular, the motivations for the importance of various types of relationships as found in four African samples: a Ghanaian urban group (n = 389), a South African multicultural, English-speaking urban group (n = 585), and two South African Setswana-speaking groups (n = 512 rural, n = 380 urban). Findings showed that the relational domains of life, namely, family, interpersonal relations, spirituality/religion, and community/society, made up a large proportion of responses on what provides meaning in life-in particular family and spirituality/religion with community/society occurring the least. The reasons for meaning experienced in various relationship types included domain-typical relational descriptors, such as contributions made or rewards received. However, many intrapersonal motives also emerged: inner well-being, happiness, joy, a sense of competence, and own growth. Material needs and harmony also surfaced as motivations for relational importance. Findings are aligned with African philosophical perspectives as far as the importance of relationships and the value attached to spirituality/religion are concerned, but contributed additionally by showing that different types of relationships vary in importance: close relationships are more important than community/societal relationships. Unearthing the reasons for the importance of relationships points toward a dialectic pattern of African individualism-collectivism in which independent and interdependent orientations flow together. Such knowledge is vital for the promotion of mental health and well-being in these contexts.
SAFE pathway and conditioning: from discovery to its effectiveness in the presence of cardiovascular risk factors
(Open access, 2020-05-05) Imamdin, A.; Hadebe, N.; Lecour, S.; South African Medical Research Council, Cape Town, South Africa
Although ischemic conditioning has been described as the most powerful strategy to protect against ischemia-reperfusion injury, its translation to the clinical setting has proved to be challenging, possibly due, at least in part, to the presence of different cardiovascular risk factors in patients, which are known to affect its efficacy. Ischemic conditioning confers cardioprotection via the activation of multiple prosurvival pathways, including the activation of the survivor activating factor enhancement (SAFE) path, which involves mediators of the innate immune system (i.e. tumor necrosis factor alpha) and key transcription factors such as the signal transducer and activator of transcription 3 (STAT3). Here, we describe the origin of the SAFE path as a key pathway in ischemic conditioning and we explore how the activation of this path may be affected in the presence of different cardiovascular risk factors.
Effectiveness of reactive focal mass drug administration and reactive focal vector control to reduce malaria transmission in the low malaria-endemic setting of Namibia: A cluster-randomised controlled, open-label, two-by-two factorial design trial
(The Lancet, 2020-04-25) Hsiang, M.S; Ntuku, H; Roberts, K.W; Dufuor, M.K; Whittemore, B; Munyaradzi, T; McCreesh, P; Medzhihradsky, O.F; Prach, L.M; Siloka, G; Siame, N; Smith Gueye, C; Schrubbe, L; Wu, L; Scott, V; Tessema, S; Greenhouse, B; Erlank, E; Koekemoer, L.L; Sturrock, H.J.W; Mwilima, A; Katokele, S; Uusiku, P; Bennett, A; Smith, J.L; Kleinschmidt, I; Mumbengegwi, D; Gosling, R; Wits Collaborating Centre for Multi-disciplinary Research on Malaria
Background: In low malaria-endemic settings, screening and treatment of individuals in close proximity to index cases, also known as reactive case detection (RACD), is practised for surveillance and response. However, other approaches could be more effective for reducing transmission. We aimed to evaluate the effectiveness of reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in the low malaria-endemic setting of Zambezi (Namibia). Methods: We did a cluster-randomised controlled, open-label trial using a two-by-two factorial design of 56 enumeration area clusters in the low malaria-endemic setting of Zambezi (Namibia). We randomly assigned these clusters using restricted randomisation to four groups: RACD only, rfMDA only, RAVC plus RACD, or rfMDA plus RAVC. RACD involved rapid diagnostic testing and treatment with artemether-lumefantrine and single-dose primaquine, rfMDA involved presumptive treatment with artemether-lumefantrine, and RAVC involved indoor residual spraying with pirimiphos-methyl. Interventions were administered within 500 m of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitoes (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA plus RAVC vs RACD only), an intention-to-treat analysis was done. For each of the three comparisons, the primary outcome was the cumulative incidence of locally acquired malaria cases. This trial is registered with ClinicalTrials.gov, number NCT02610400. Findings: Between Jan 1, 2017, and Dec 31, 2017, 55 enumeration area clusters had 1118 eligible index cases that led to 342 interventions covering 8948 individuals. The cumulative incidence of locally acquired malaria was 30·8 per 1000 person-years (95% CI 12·8-48·7) in the clusters that received rfMDA versus 38·3 per 1000 person-years (23·0-53·6) in the clusters that received RACD; 30·2 per 1000 person-years (15·0-45·5) in the clusters that received RAVC versus 38·9 per 1000 person-years (20·7-57·1) in the clusters that did not receive RAVC; and 25·0 per 1000 person-years (5·2-44·7) in the clusters that received rfMDA plus RAVC versus 41·4 per 1000 person-years (21·5-61·2) in the clusters that received RACD only. After adjusting for imbalances in baseline and implementation factors, the incidence of malaria was lower in clusters receiving rfMDA than in those receiving RACD (adjusted incidence rate ratio 0·52 [95% CI 0·16-0·88], p=0·009), lower in clusters receiving RAVC than in those that did not (0·48 [0·16-0·80], p=0·002), and lower in clusters that received rfMDA plus RAVC than in those receiving RACD only (0·26 [0·10-0·68], p=0·006). No serious adverse events were reported. Interpretation: In a low malaria-endemic setting, rfMDA and RAVC, implemented alone and in combination, reduced malaria transmission and should be considered as alternatives to RACD for elimination of malaria.
Grapefruit juice improves glucose intolerance in streptozotocin-induced diabetes by suppressing hepatic gluconeogenesis.
(Springer, 2016-03) Hayanga, J.A; Ngubane, S.P.; Murunga, A.N.; Owira, P.M; The study was supported by a grant from the Medical Research Council of South African, and there is no conflict of interest to declare.
Purpose Hypoglycemic effects of grapefruit juice (GFJ) are widely recognized, but the mechanism(s) by which GFJ lowers blood glucose levels have not previously been investigated. Methods Wistar rats [250–300 g body weight (BW)] were divided into eight groups (n = 7). Group 1 animals were orally treated with 3.0 ml/kg BW of distilled water for 60 days, while groups 3, 4, 5, 6 were similarly treated with 3.0 ml/kg BW of GFJ. Groups 4 and 7 as well as 2, 5, 6 and 8 were given 45.0 and 60.0 mg/kg BW intraperitoneal injections streptozotocin, respectively, while groups 2 and 6 animals were additionally injected with insulin (4.0 units/kg, S.C., b.d), respectively. Fasting blood glucose (FBG) and glucose tolerance tests were done. Hepatic glycogen content and glucokinase, glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were measured in homogenized liver tissues. Results Diabetic rats, groups 2 and 4–8 exhibited significantly reduced weight gain but increased polydipsia compared to controls. FBG was significantly increased in diabetic rats compared to controls but were significantly improved in GFJ-treated—compared to non-treated—diabetic rats. Similarly, diabetic rats showed significant glucose intolerance compared to controls which was improved by GFJ treatment. GFJ treatment did not improve fasting plasma insulin in diabetic rats. GFJ treatment significantly elevated glucokinase activity and hepatic glycogen concentrations but suppressed the activities of G6Pase and PEPCK, respectively, in diabetic animals. Conclusion These findings show that GFJ is not insulinotropic but improves glucose intolerance in diabetic rats by suppressing hepatic gluconeogenesis.
The use of directed evolution to create a stable and immunogenic recombinant BCG expressing a modified HIV-1 Gag antigen.
(2014-07-25) Chapman, Rosamund; Bourn, William R; Shephard, Enid; Stutz, Helen; Douglass, Nicola; Mgwebi, Thandi; Meyers, Ann; Chin'ombe, Nyasha; Williamson, Anna-Lise
Numerous features make Mycobacterium bovis BCG an attractive vaccine vector for HIV. It has a good safety profile, it elicits long-lasting cellular immune responses and in addition manufacturing costs are affordable. Despite these advantages it is often difficult to express viral antigens in BCG, which results in genetic instability and low immunogenicity. The aim of this study was to generate stable recombinant BCG (rBCG) that express high levels of HIV antigens, by modification of the HIV genes. A directed evolution process was applied to recombinant mycobacteria that expressed HIV-1 Gag fused to the green fluorescent protein (GFP). Higher growth rates and increased GFP expression were selected for. Through this process a modified Gag antigen was selected. Recombinant BCG that expressed the modified Gag (BCG[pWB106] and BCG[pWB206]) were more stable, produced higher levels of antigen and grew faster than those that expressed the unmodified Gag (BCG[pWB105]). The recombinant BCG that expressed the modified HIV-1 Gag induced 2 to 3 fold higher levels of Gag-specific CD4 T cells than those expressing the unmodified Gag (BCG[pWB105]). Mice primed with 10(7) CFU BCG[pWB206] and then boosted with MVA-Gag developed Gag-specific CD8 T cells with a frequency of 1343±17 SFU/10(6) splenocytes, 16 fold greater than the response induced with MVA-Gag alone. Levels of Gag-specific CD4 T cells were approximately 5 fold higher in mice primed with BCG[pWB206] and boosted with MVA-Gag than in those receiving the MVA-Gag boost alone. In addition mice vaccinated with BCG[pWB206] were protected from a surrogate vaccinia virus challenge.

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