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    The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment
    (Elsevier, 2021-03) Jansen van Vuren, E.; Steyn, S.F.; Brink, C.B.; Möller, M.; Viljoen, F.P.; Harvey, B.H.; Brian H. Harvey: South African MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa
    The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses. Several neurological and psychiatric disorders are characterized by immune-inflammatory states, while treatments for these disorders have distinct anti-inflammatory properties and effects. With inflammation being a common contributing factor in SARS-CoV-2, as well as psychiatric disorders, treatment of either condition may affect disease progression of the other or alter response to pharmacological treatment. In this review, we elucidate how viral infections could affect pre-existing psychiatric conditions and how pharmacological treatments of these conditions may affect overall progress and outcome in the treatment of SARS-CoV-2. We address whether any treatment-induced benefits and potential adverse effects may ultimately affect the overall treatment approach, considering the underlying dysregulated neuro-inflammatory processes and potential drug interactions. Finally, we suggest adjunctive treatment options for SARS-CoV-2-associated neuro-psychiatric symptoms.
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    Epidemiology of human metapneumovirus-associated lower respiratory tract infections in African children: Systematic review and meta-analysis
    (Wolters Kluwer, 2021-05-01) Ramocha, L.M.; Mutsaerts, E.A.M.L.; Verwey, C.; Madhi, S.; Lesego M Ramocha: South African Medical Research Council: Vaccines and Infectious Diseases Analytical Research Unit (VIDA), University of the Witwatersrand, Faculty of Health Science, Johannesburg, South Africa
    Background: Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the epidemiology of hMPV-associated LRTI, including severe acute respiratory infection (SARI) hospitalization or clinically diagnosed severe pneumonia, in African children under 5 years of age. Methods: We searched Science Direct, PubMed, Cochrane Central, Scopus, and WHO regional databases using the terms "("Human metapneumovirus" AND "Africa") OR ("hMPV" AND "Africa")" up to September 17, 2020. Other sources included ClinicalTrials.gov to obtain unpublished data. Studies were included if children were less than 5 years of age and hospitalized with hMPV-associated LRTI, SARI or if clinically diagnosed with severe pneumonia in the community. The main outcomes were prevalence of hMPV identified among children with hospitalized LRTI or SARI. We further calculated odds ratios for hMPV in cases with LRTI compared with non-LRTI controls. Pooled results were calculated using a random-effects model. Results: Thirty studies were eligible for inclusion in the review. The prevalence of hMPV-LRTI/SARI among hospitalized and severe pneumonia cases was 4.7% [95% confidence interval (CI): 3.9-5.6, I2 = 95.0]. The case-control studies indicated that hMPV was 2.0-fold (95% CI: 0.9-4.4) more likely to be identified in LRTI cases (10.3%) than controls (6.0%). Three of 5 studies reported hMPV-associated LRTI case fatality risk, with a pooled estimate of 1.3% (95% CI: 0.3-2.9; I2 = 49). Conclusions: hMPV was associated with approximately 5% of LRTI/SARI hospitalizations or severe pneumonia cases in Africa.
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    Colorectal cancer genetics, incidence and risk factors: In search for targeted therapies
    (DovePress, 2020-10-09) Hull, R.; Francies, F.Z.; Oyomno, M.; Dlamini, Z.; Rodney Hull, Flavia Zita Francies, Zodwa Dlamini: SAMRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Hatfield 0028, South Africa.
    Each year, colorectal cancers (CRCs) affect over a quarter of a million people. The risk of developing CRC in industrialized nations is approximately 5%. When the disease is localised, treatment success rates range from 70-90%; however, advanced CRC has a high mortality rate, consistently ranking in the top three causes of cancer-related deaths. There is a large geographic difference in global distribution, and CRC is predominantly associated with developed countries and a Western lifestyle and diet. As such, the developed world accounts for more than 63% of all cases of CRC. Geographic variations also predict cancer outcomes, which differ between racial and ethnic groups. This variation is due to inequalities in wealth, differences in the exposure to risk factors and barriers to high-quality cancer prevention, early detection and treatment. The aim of this paper was to review CRC in low- and middle-income countries such as South Africa, India, Brazil and China, and compare them with high-income countries such as the United States of America and the United Kingdom. It is important to note that these economically less developed countries, with historically low CRC rates, are experiencing an increased frequency of CRC. The review also discusses biological markers and genetic pathways involved in the development of colorectal cancer. Genes known to be responsible for the most common forms of inherited CRCs have also been identified but more remain to be identified. This would provide more candidate genes to be added to known biomarkers. CRC burden can be controlled through the widespread application of existing knowledge, such as reduced smoking habits, vaccination, early detection and promoting physical activity, accompanied by a healthy diet. An increased understanding of the molecular mechanisms and events underlying colorectal carcinogenesis will enable the development of new targets and therapeutic drugs.
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    Bacillus sp. CSK2 produced thermostable alkaline keratinase using agro-wastes: Keratinolytic enzyme characterization
    (BMC, 2020-12-14) Nnolim, N.E.; Nwodo, U.U.; Uchechukwu U Nwodo: SAMRC Microbial Water Quality Monitoring Centre, University of Fort Hare, Alice, 5700, South Africa.
    Background: Chicken feathers are the most abundant agro-wastes emanating from the poultry processing farms and present major concerns to environmentalists. Bioutilization of intractable feather wastes for the production of critical proteolytic enzymes is highly attractive from both ecological and biotechnological perspectives. Consequently, physicochemical conditions influencing keratinase production by Bacillus sp. CSK2 on chicken feathers formulation was optimized, and the keratinase was characterized. Results: The highest enzyme activity of 1539.09 ± 68.14 U/mL was obtained after 48 h of incubation with optimized conditions consisting of chicken feathers (7.5 g/L), maltose (2.0 g/L), initial fermentation pH (5.0), incubation temperature (30 °C), and agitation speed (200 rpm). The keratinase showed optimal catalytic efficiency at pH 8.0 and a temperature range of 60 °C - 80 °C. The keratinase thermostability was remarkable with a half-life of above 120 min at 70 °C. Keratinase catalytic efficiency was halted by ethylenediaminetetraacetic acid and 1,10-phenanthroline. However, keratinase activity was enhanced by 2-mercaptoethanol, dimethyl sulfoxide, tween-80, but was strongly inhibited by Al3+ and Fe3+. Upon treatment with laundry detergents, the following keratinase residual activities were achieved: 85.19 ± 1.33% (Sunlight), 90.33 ± 5.95% (Surf), 80.16 ± 2.99% (Omo), 99.49 ± 3.11% (Ariel), and 87.19 ± 0.26% (Maq). Conclusion: The remarkable stability of the keratinase with an admixture of organic solvents or laundry detergents portends the industrial and biotechnological significance of the biocatalyst.
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    Foam cells control Mycobacterium tuberculosis infection
    (Frontiers, 2020-07-09) Agarwal, P.; Combes, T.W.; Shojaee-Moradie, F.; Fielding, B.; Gordon, S.; Mizrahi, V.; Martinez, F.O.; South African Medical Research Council/National Health Laboratory Service/University of Cape Town, Molecular Mycobacteriology Research Unit, Division of Medical Microbiology, Department of Pathology, Department of Science and Innovation/National Research Foundation, Centre of Excellence for Biomedical TB Research and Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
    Mycobacterium tuberculosis (Mtb) infects macrophages and macrophage-derived foam cells, a hallmark of granulomata in tuberculous lesions. We analyzed the effects of lipid accumulation in human primary macrophages and quantified strong triglyceride and phospholipid remodeling which depended on the dietary fatty acid used for the assay. The enrichment of >70% in triglyceride and phospholipids can alter cell membrane properties, signaling and phagocytosis in macrophages. In conventional macrophage cultures, cells are heterogeneous, small or large macrophages. In foam cells, a third population of 30% of cells with increased granularity can be detected. We found that foam cell formation is heterogenous and that lipid accumulation and foam cell formation reduces the phagocytosis of Mtb. Under the conditions tested, cell death was highly prevalent in macrophages, whereas foam cells were largely protected from this effect. Foam cells also supported slower Mtb replication, yet this had no discernible impact on the intracellular efficacy of four different antitubercular drugs. Foam cell formation had a significant impact in the inflammatory potential of the cells. TNF-α, IL-1β, and prototypical chemokines were increased. The ratio of inflammatory IL-1β, TNF-α, and IL-6 vs. anti-inflammatory IL-10 was significantly higher in response to Mtb vs. LPS, and was increased in foam cells compared to macrophages, suggestive of increased pro-inflammatory properties. Cytokine production correlated with NF-κB activation in our models. We conclude that foam cell formation reduces the host cell avidity for, and phagocytosis of, Mtb while protecting the cells from death. This protective effect is associated with enhanced inflammatory potential of foam cells and restricted intracellular growth of Mtb.

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