A data management plan for the NESHIE observational study

With regard to the use and transfer of research participants’ personal information, samples and other data nationally and internationally, it is necessary to construct a data management plan. One of the key objectives of a data management plan is to explain the governance of clinical, biochemical, laboratory, molecular and other sources of data according to the regulations and policies of all relevant stakeholders. It also seeks to describe the processes involved in protecting the personal information of research participants, especially those from vulnerable populations. In most data management plans, the framework therefore consists of describing the collection, organization, use, storage, contextualization, preservation, sharing and access of/to research data and/or samples. It may also include a description of data management resources, including those associated with analyzed samples, and identifies responsible parties for the establishment, implementation and overall management of the data management strategy. Importantly, the data management plan serves to highlight potential problems with the collection, sharing, and preservation of research data. However, there are different forms of data management plans and requirements may vary due to funder guidelines and the nature of the study under consideration. This paper leverages the detailed data management plans constructed for the ‘NESHIE study’ and is a first attempt at providing a comprehensive template applicable to research focused on vulnerable populations, particularly those within LMICs, that includes a multi-omics approach to achieve the study aims. More particularly, this template, available for download as a supplementary document, provides a modifiable outline for future projects that involve similar sensitivities, whether in clinical research or clinical trials. It includes a description of the management not only of the data generated through standard clinical practice, but also that which is generated through the analysis of a variety of samples being collected from research participants and analyzed using multi-omics approaches

A data management plan for the NESHIE observational study

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.With regard to the use and transfer of research participants’ personal information, samples and other data nationally and internationally, it is necessary to construct a data management plan. One of the key objectives of a data management plan is to explain the governance of clinical, biochemical, laboratory, molecular and other sources of data according to the regulations and policies of all relevant stakeholders. It also seeks to describe the processes involved in protecting the personal information of research participants, especially those from vulnerable populations. In most data management plans, the framework therefore consists of describing the collection, organization, use, storage, contextualization, preservation, sharing and access of/to research data and/or samples. It may also include a description of data management resources, including those associated with analyzed samples, and identifies responsible parties for the establishment, implementation and overall management of the data management strategy. Importantly, the data management plan serves to highlight potential problems with the collection, sharing, and preservation of research data. However, there are different forms of data management plans and requirements may vary due to funder guidelines and the nature of the study under consideration. This paper leverages the detailed data management plans constructed for the ‘NESHIE study’ and is a first attempt at providing a comprehensive template applicable to research focused on vulnerable populations, particularly those within LMICs, that includes a multi-omics approach to achieve the study aims. More particularly, this template, available for download as a supplementary document, provides a modifiable outline for future projects that involve similar sensitivities, whether in clinical research or clinical trials. It includes a description of the management not only of the data generated through standard clinical practice, but also that which is generated through the analysis of a variety of samples being collected from research participants and analyzed using multi-omics approaches.The South African Medical Research Council and the Bill and Melinda Gates Foundation.http://www.frontiersin.org/Geneticsam2024ImmunologyNon

Adverse effects of copper, manganese and mercury, alone and in mixtures on the aorta and heart of Spraque-Dawley rats

Cardiovascular diseases (CVD) are a common global cause of death and are therefore a major health concern. Inhaled or ingested environmental heavy metals contribute to the development of CVD. The aim of this study was to address the limited information available on the effect of relevant dosages of metals in mixtures. Three metals with reported effects on the cardiovascular system (CVS) were identified, and these metals were copper (Cu), manganese (Mn) and mercury (Hg). In Sprague-Dawley rats, the adverse effects of copper (Cu), manganese (Mn) and mercury (Hg), alone and as part of mixtures, on the blood parameters, the aorta and heart were investigated. Forty-eight male Sprague-Dawley rats were randomly divided into eight groups (n = 6): control, Cu, Mn, Hg, Cu + Mn, Cu + Hg, Mn + Hg and Cu, Mn + Hg. The seven experimental groups received the metal mixtures at 100 times the World Health Organisation (WHO) safety limit for drinking water (2 mg/L for Cu, 0.4 mg/L for Mn and 0.06 mg/L for Hg) via oral gavage for 28 days. After 28 days, compared with the control, red blood cell levels were increased for Cu + Hg. All other measured blood parameters were unchanged. Morphological changes in the tunica media were connective tissue deposition and an abundance of collagen type I in the metal exposed aortic tissues. In the cardiac tissue of metal-exposed rats, changes in the cardiomyocyte and myofibrillar arrangement, with an increase in collagen type I and III was observed. Ultrastructurally, the aortic collagen and elastin band arrangement and the cardiac mitochondrial and myofibrillar arrangement and structures were altered in the experimental groups. These changes indicated that exposure to these metals in rats caused minor changes in the blood parameters, however, the changes in tissue and cellular structure indicated an increased risk for the development of CVD.https://journals.sagepub.com/home/tihhj2023AnatomyPhysiologySDG-03:Good heatlh and well-bein

Open access and its potential impact on public health – a South African perspective

Traditionally, access to research information has been restricted through journal subscriptions. This means that research entities and individuals who were unable to afford subscription costs did not have access to journal articles. There has however been a progressive shift toward electronic access to journal publications and subsequently growth in the number of journals available globally. In the context of electronic journals, both open access and restricted access options exist. While the latter option is comparable to traditional, subscription-based paper journals, open access journal publications follow an “open science” publishing model allowing scholarly communications and outputs to be publicly available online at no cost to the reader. However, for readers to enjoy open access, publication costs are shifted elsewhere, typically onto academic institutions and authors. SARS-CoV-2, and the resulting COVID-19 pandemic have highlighted the benefits of open science through accelerated research and unprecedented levels of collaboration and data sharing. South Africa is one of the leading open access countries on the African continent. This paper focuses on open access in the South African higher education research context with an emphasis on our Institution and our own experiences. It also addresses the financial implications of open access and provides possible solutions for reducing the cost of publication for researchers and their institutions. Privacy in open access and the role of the Protection of Personal Information Act (POPIA) in medical research and secondary use of data in South Africa will also be discussed.The South African Medical Research Council Extramural Unit for Stem Cell Research and Therapy and the University of Pretoria through the Institute for Cellular and Molecular Medicine and the Bill and Melinda Gates Foundation.https://www.frontiersin.org/journals/research-metrics-and-analyticshj2022Immunolog

Oxidative and haemostatic effects of copper, manganese and mercury, alone and in combination at physiologically relevant levels: an ex vivo study

Water contamination with metals due to anthropogenic activity is increasing and subsequent exposure increases the risk of associated toxicity. Exposure is not limited to a single metal but usually involves mixtures of different metals at different concentrations. Little is known about the contribution of this type of exposure, in humans, to the development of non-communicable diseases such as cardiovascular disease, and an increased risk to thrombosis. The World Health Organization has established limits for metal levels in drinking water and this includes levels for copper (Cu), manganese (Mn) and mercury (Hg). In this study, at 100X these limits, the ability of the metals’ oxidative effects as catalysts of the Fenton reaction and/or ability to bind glutathione (GSH) were determined. The haemostatic effects of these metals, alone and in combination, at the World Health Organization limit were then evaluated. The ultrastructural and viscoelastic alterations of exposed ex vivo whole blood were also evaluated using scanning electron microscopy and thromboelastography® (TEG), respectively. Cu, alone and in combination with Mn and/or Hg, induced hydroxyl radical formation and reduced GSH levels. Ex vivo exposure caused deformation of erythrocytes and accelerated platelet activation especially for Cu, alone and in combination, with Mn. Reduction in the lysis potential of the clot was also observed for all combinations, especially Cu in combination with Hg as well as Mn alone. Although the TEG findings were not statistically significant, the trends indicate that the exposure to these metals, alone and in combination, adversely affects thrombus formation in ex vivo blood, thereby potentially increasing the risk in exposed individuals for thrombosis.The National Research Foundation under grant number 92768.https://journals.sagepub.com/home/hethj2019AnatomyPhysiolog

The NESHIE and CP Genetics Resource (NCGR): A database of genes and variants reported in neonatal encephalopathy with suspected hypoxic ischemic encephalopathy (NESHIE) and consequential cerebral palsy (CP)

DATA AVAILABILTY : All data generated or analysed during this study are included in this published article, supplementary information files, and the NCGR database repository. Access to the NCGR database is available at http://ncgr.bi.up.ac.za/. Additional data will be made available on request.SUPPLEMENTARY DATA : SUPPLEMENTARY FIG. 1. User input for a complex query generated using NCGR's filter functionality to prioritise genes likely to predispose individuals to NESHIE. Abbreviations: CP: cerebral palsy; NESHIE: neonatal encephalopathy with suspected hypoxic ischemic encephalopathy; HPO: human phenotype ontology; NCGR: NESHIE and CP genetics resource.SUPPLEMENTARY FIG. 2. Protein-protein interaction network constructed using genes that were prioritised based on evidence of potential involvement in a genetic predisposition to neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE). Protein products of the input set of genes are represented by blue nodes. Additional direct and secondary interactors of the input set are represented in grey.SUPPLEMENTARY DATA A. Methods used to perform gene ontology enrichment and protein-protein interaction network analyses.SUPPLEMENTARY DATA B. Gene Ontology enrichment resultsSUPPLEMENTARY TABLE 1. Variant Details table data.SUPPLEMENTARY TABLE 2. Ensembl Variant Effect Prediction table data.SUPPLEMENTARY TABLE 3. Gene Details table data.SUPPLEMENTARY TABLE 4. Gene Human Phenotype Ontology table data.SUPPLEMENTARY TABLE 5. MutationTaster Variant Effect Prediction table data.SUPPLEMENTARY TABLE 6. Study Details table data.SUPPLEMENTARY TABLE 7. Study Findings table data.Neonatal encephalopathy (NE) with suspected hypoxic ischaemic encephalopathy (HIE) (NESHIE) is a complex syndrome occurring in newborns, characterised by altered neurological function. It has been suggested that genetic variants may influence NESHIE susceptibility and outcomes. Unlike NESHIE, for which a limited number of genetic studies have been performed, many studies have identified genetic variants associated with cerebral palsy (CP), which can develop from severe NESHIE. Identifying variants in patients with CP, as a consequence of NESHIE, may provide a starting point for the identification of genetic variants associated with NESHIE outcomes. We have constructed NCGR (NESHIE and CP Genetics Resource), a database of genes and variants reported in patients with NESHIE and CP (where relevant to NESHIE), for the purpose of collating and comparing genetic findings between the two conditions. In this paper we describe the construction and functionality of NCGR. Furthermore, we demonstrate how NCGR can be used to prioritise genes and variants of potential clinical relevance that may underlie a genetic predisposition to NESHIE and contribute to an understanding of its pathogenesis.The Bill & Melinda Gates Foundation, Seattle, USA; the South African Medical Research Council, Cape Town, South Africa; and the University of Pretoria through the Institute for Cellular and Molecular Medicine.https://www.elsevier.com/locate/ygenohj2023BiochemistryGeneticsImmunologyMicrobiology and Plant Patholog

Conservation conundrum – red listing of subtropical-temperate coastal forested wetlands of South Africa

Africa’s range-restricted and transitional subtropical-temperate coastal forested wetlands are facing interlinking threats of climate and anthropogenic pressures. We assessed their conservation status using the criteria of the International Union for Conservation of Nature (IUCN). Their total areal extent was hind-casted to the reference epoch 2000, followed by the quantification of subsequent total losses in areal extents for the epochs 2005, 2008, 2011 and 2017. South Africa had 120 km2 of coastal swamp and floodplain forests in 2000 of which the majority (116.5 km2) occurred on the Maputaland Coastal Plain (MCP). By 2011, 20% of the areal extent was lost, and at the lowest rate of decline we estimate that ≥ 80% of the rest will be lost in the next 50 years. An ecosystem collapse assessment therefore indicated that the habitat is very likely Critically Endangered. Fragmentation and types of transformations were used as degradation indices to show functional collapse. These results showed that forest patches became increasingly fragmented, from 511 to 1 145 patches between 2000 and 2017 and that > 23% of the areal extent showed severe transformation. Several faunal species, with a close association to the forested wetlands of the MCP, are considered threatened with numbers declining because of transformation to timber plantations or agriculture and coupled with a prolonged drought. Of these, a sub-species of the Samango monkey, Cercopithecus mitis erythrarchus, considered to be a primary ecosystem engineer of the habitat, was red listed with a restricted distribution, being endemic, Near Threatened and declining. Also under pressure, because of habitat fragmentation and degradation is the Peregrine crab (Varuna litterata), a euryhaline species requiring connectivity across the land-seascape, ranging from freshwater forested wetlands to estuarine and off-shore environments. Functionally, these coastal forested wetlands are therefore also considered Critically Endangered. The final IUCN conservation status of South Africa’s subtropical-temperate coastal forested wetlands are recommended to be very likely Critically Endangered. Irrespective of 62% of the areal extent of these forested wetlands being within protected areas, severe degradation (metrics of fragmentation and transformation) were observed even inside these areas for the past two decades. The conservation conundrum is that despite existing legislation and management measures, there has been no stop or reversal of the negative trends to date. As a supplementary method, we therefore recommend a transdisciplinary community-based approach to conservation practice, continued and improved monitoring of the habitat losses, the identifying priority areas for rehabilitation and addressing data deficiencies in important species associations.CSIR’s Parliamentary Grant Project P1BEO00/P1CCS02, titled “Marine Observational and Predictive System Capabilities (MAROPS)”; as well as the African Union Commission (AUC) Global Monitoring for Environment and Security (GMES) MARCOSOUTH (K8MARCO). The Department of Science and Innovation (DSI) and National Research Foundation (NRF) Chair in Shallow Water Ecosystems (UID 84375) supported time of Prof. Janine Adams.https://www.elsevier.com/locate/ecolindam2022Geography, Geoinformatics and Meteorolog

Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy should not be discontinued in low- and middle-income countries

Perinatal asphyxia is a major cause of death and disability in children. Therapeutic hypothermia (TH) has become a standard of care for newborn infants who have sustained hypoxic ischaemic encephalopathy (HIE) due to perinatal asphyxia. There is compelling evidence to support this approach. A Cochrane systematic review of 11 prospective randomised controlled trials including 1 505 newborns showed that TH started within 6 hours of birth in infants with HIE significantly decreased mortality and neurodevelopmental disability in survivors.http://www.samj.org.zadm2022ImmunologyPaediatrics and Child Healt

Rarefaction as a tool to determine variant diversity in monogenetic disorders

Genetic diversity is a well-described concept within many biological disciplines. However, mathematical models determining genetic diversity are often applied within ecological disciplines and are rarely explored within the medical field. Given that genetically associated disorders and complications can occur at high frequency in developing countries, the primary aim of this study was to determine whether or not diversity theory could be applied to disease-associated variants. Two monogenic disorders were selected for this purpose one commonly observed disorder known as cystic fibrosis (CF), and one rare disorder known as metachromatic leukodystrophy (MLD). Despite being a common monogenic disorder, the clinical and molecular presentation of CF in the different population groups of South Africa is largely unknown. Thus, the medical records of 45 CF patients attending the Steve Biko Academic Hospital CF clinic were investigated to better understand the manifestation of this disorder in these patients. Additionally, molecular data was collected for both CF and MLD through published reports and analysed via the Shannon-Weaver, Simpson, Simpson Diversity, and rarefaction diversity methods. The rarefaction method was found to be the most informative measure of diversity and a potentially powerful tool to employ in the development and/or refinement of population-specific screening panels.Dissertation (MSc)--University of Pretoria, 2015.ImmunologyMScUnrestricte