Recent Submissions

  • Publication
    Synthesis and biological evaluation of 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones
    (Elsevier, 2019) Olawode, E.O; Tandlich, R; Prinsloo, E; Isaacs, M; Hoppe, H; Seldon, R; Warner, D.F; Steenkamp, V; Kaye, P.T; Digby F Warner: Molecular Mycobacteriology Research Unit, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town
  • Publication
    Comparison of major depression diagnostic classification probability using the SCID, CIDI, and MINI diagnostic interviews among women in pregnancy or postpartum: An individual participant data meta-analysis
    (Wiley, 2019-12) Levis, B; Mcmillan, D; Ying, Sun; He, Che; Rice, D.B; Krishnan, A; Wu, Y; Azar, M; Sanchez, T.A; Chiovitti, M.J; Bhandari, P.M; Neupane, D; Saadat, N; Riehm, K.E; Imran, M; Boruff, J.T; Cuijpers, P; Gilbody, S; Loannidis, J.P.A; Kloda, L.A; Patten, S.B; Shrier, I; Ziegelstein, R.C; Comeau, L; Mitchell, N.D; Tonelli, M; Vigod, S.N; Aceti, F; Alvarado, R; Alvarado-Esquivel, C; Bakare, M.O; Barnes, J; Beck, C.T; Bindt, C; Boyce, P.M; Bunevicius, A; Couto, T.C.E; Chaudron, L.H; Correa, H; Pinheiro de Figueiredo, F; Eapen, V; Fernandes, M; Figueiredo, B; Fisher, J.R.W; Garcia-Esteve, L; Giardinelli, L; Helle, N; Howard, L.M; Khalifa, D.S; Kohlhoff, J; Kusminskas, L; Kozinszky, Z; Lelli, L; Leonardou, A.A; Lewis, B.A; Maes, M; Meuti, V; Nakić Radoš 59, S; García, P.N; Nishi, D; Andjafono, D.O.L.E; Robertson-Blackmore, E; Rochat, T.J; Rowe, H.J; Siu, B.W.M; Skalkidou, A; Stein, A; Stewart, R.C; Su, K.P; Sundström-Poromaa, I; Tadinac, M; Tandon, S.D; Tendais, I; Thiagayson, P; Töreki, A; Torres-Giménez, A; Tran, T.D; Trevillion, K; Turner, K; Vega-Dienstmaier, J.M; Wynter, K; Yonkers, K.A; Benedetti, A; Thombs, B.D; MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. Results: Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased.
  • Publication
    Structure elaboration of isoniazid: Synthesis, in silico molecular docking and antimycobacterial activity of isoniazid–pyrimidine conjugates
    (Springer Nature, 2019-10-18) Kaur, H; Singh, L; Chibale, K; Singh, K; Kelly Chibale: South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, 701, South Africa.
    Designing small molecule-based new drug candidates through structure modulation of the existing drugs has drawn considerable attention in view of inevitable emergence of resistance. A new series of isoniazid-pyrimidine conjugates were synthesized in good yields and evaluated for antitubercular activity against the H37Rv strain of Mycobacterium tuberculosis using the microplate Alamar Blue assay. Structure-anti-TB relationship profile revealed that conjugates 8a and 8c bearing a phenyl group at C-6 of pyrimidine scaffold were most active (MIC99 10 µM) and least cytotoxic members of the series. In silico docking of 8a in the active site of bovine lactoperoxidase as well as a cytochrome C peroxidase mutant N184R Y36A revealed favorable interactions similar to the heme enzyme catalase peroxidase (KatG) that activates isoniazid. This investigation suggests a rationale for further work on this promising series of antitubercular agents.
  • Publication
    Human leukocyte antigen (HLA) diversity and clinical applications in South Africa
    (South African Medical Journal (SAMJ), 2019-09-10) Mellet, J; Tshabalala, M; Agbedare, O; Meyer, P.W.A; Gray, C.M; Pepper, M.S; Mellet J, Tshabalala M, Agbedare O: Institute for Cellular and Molecular Medicine, Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, South Africa.
    The major histocompatibility complex, known as the human leukocyte antigen (HLA) complex in humans, forms an integral component of adaptive T cell immunity by presenting self and non-self peptides to the T cell receptor, thereby allowing clonal expansion of responding peptide-specific CD4+ and CD8+ T cells. HLA likewise forms an integral part of the innate immune response through the binding of killer-cell immunoglobulin-like receptor (KIR) molecules, which regulate the response of natural killer (NK) cells. The HLA complex is found on the short arm of chromosome 6 and is the most polymorphic region in the human genome. Africans are genetically more diverse than other populations; however, information on HLA diversity among southern Africans, including South African populations, is limited. Paucity of African HLA data limits our understanding of disease associations, the ability to identify donor-recipient matches for transplantation and the development of disease-specific vaccines. This review discusses the importance of HLA in the clinical setting in South Africans and highlights how tools such as HLA imputation might augment standard HLA typing methods to increase our understanding of HLA diversity in our populations, which will better inform disease association studies, donor recruitment strategies into bone marrow registries and our understanding of human genetic diversity in South Africa.
  • Publication
    Associations of early-life growth with health using an allostatic load score in young, urban African adults: Birth to twenty plus cohort
    (Cambridge University Press, 2019-08) McGowan, C.J; Norris, S.A; Craig J McGowan & SAMRC Shane A Norris: Developmental Pathways for Health Research Unit, Department of Paediatrics, University of the Witwatersrand, Johannesburg, South Africa.
    Growth in early life is associated with various individual health outcomes in adulthood, but limited research has been done on associations with a more comprehensive measure of health. Combining information from multiple biological systems, allostatic load (AL) provides such a quantitative measure of overall physiological health. We used longitudinal data from the Birth to Twenty Plus cohort in South Africa to calculate an AL score at age 22 years and examined associations with birth weight and linear growth and weight gain from age 0 to 2 years and 2 to 5 years, as attenuated by trajectories of body mass index and pubertal development in later childhood and adolescence. Differences in total AL score between males and females were small, though levels of individual biological factors contributing to AL differed by sex. Increased weight gain from age 2 to 5 years among males was associated with an increased risk of high AL, but no other early-life measures were associated with AL. Increased adiposity through childhood and adolescence in females was associated with higher AL in early adulthood. These results illustrate that patterns of early-life growth are not consistently associated with higher AL. While more research is needed to link AL in young adulthood to later health outcomes, these results also suggest increased adiposity during childhood and adolescence represents a potential early sign of later physiological risk.

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