Browsing by Author "Abrahams, Shameemah"

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    Open Access
    Exploring the potential for biomarkers to aid forensic diagnosis of traumatic brain injury (TBI) – a systematic literature review and meta-analysis
    (2024) Velcich, Carly; Abrahams, Shameemah; Heathfield, Laura; Molefe, Itumeleng
    Background: Traumatic brain injury (TBI) is a prevalent condition worldwide. Understanding its pathophysiology is imperative for clinical diagnosis, treatment, and cause of death determination. Biomarkers could offer potential insight. Proteins involved in neuroinflammation, such as systemic inflammatory biomarkers interleukin (IL)-1β, IL-6, and IL-10 and astroglia-associated biomarkers S100 Calcium-Binding Protein B (S100β) and Glial Fibrillary Acidic Protein (GFAP), have been assessed as potential TBI biomarkers. The aim of this review was to evaluate recent articles that investigated these biomarkers in relation to TBI and relate this to a forensic diagnostic context. Methods: This review included 44 peer-reviewed articles from three major literature databases published from 2018 onwards, that investigated either IL-1β, IL-6, IL-10, GFAP, S100β, or a combination thereof, in relation to TBI. Studies conducted in a clinical or forensic setting were included. A meta-analysis was conducted on a subset of these studies. Results: Majority of the biomarkers were elevated in TBI versus control groups. The most promising biomarkers were GFAP and S100β, which in addition to being elevated also correlated with unfavourable outcomes and TBI severity. GFAP alone was increased in TBI patients with positive CT scans. The ILs had inconclusive results due to minimal studies and inconsistent study designs. A wide range of biomarker expression levels were noted across all articles (from 0.01 to 1.5 million pg/mL). The meta-analysis yielded a pooled effect size of 0.97. Discussion: Inconsistencies in results could potentially be explained by heterogenous TBI and control groups, various body specimens, and different immunoassays used. Thus, each biomarker should be investigated systematically whilst keeping other variables consistent to ensure definitive conclusions. Overall, none of the proteins could function as biomarkers of TBI alone. However, the meta-analysis did indicate a moderately significant association between biomarker levels and TBI occurrence. Future studies are needed to corroborate the findings.
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    Open Access
    The correlation between cranial fractures and brain trauma: a retrospective study
    (2024) Sakambana, Sinoyolo; Mole, Calvin; Abrahams, Shameemah
    Traumatic brain injury (TBI) is a global public health concern. TBI has been noted to co-occur with cranial fractures, however this is not always case. At present, there is a gap in literature regarding the correlative relationship between the presence of cranial fracture and brain trauma. The knowledge and understanding of this correlation is imperative for autopsy examinations where pathologists have to determine the cause of death of an individual. Furthermore, in cases where the skeleton is the only tissue that is available for examination, anthropologists will be able to apply this knowledge to infer the presence of brain trauma at death. Therefore, the current study aimed to assess the correlation of cranial fracture and brain injury in cases of blunt force trauma. This was achieved through a retrospective review of blunt force head injury cases of blunt force head injury examined at Salt River Mortuary, Cape Town between 01 January 2015 and 31 December 2019. Co-occurrence of cranial fractures with brain trauma was prevalent in the current study, accounting for 64% of the recorded cases. A significant association was found between age at death and the presence of brain trauma (p = 0.042), with majority of individuals with brain trauma ranging between 18 to 49 years of age. Similarly, a significant association was found between the presence of cranial fractures and age (p = <0.001). A significant association was found between the presence of cranial fractures and brain trauma to the frontal, parietal and temporal lobes (p = <0.001). Moreover, fracture type was significantly associated with the presence of brain trauma. Fractures of the cranial base have an increased risk of being associated with traumatic brain injury compared to the fractures in other regions. Individuals presenting with cranial fracture are 4.48 times more likely to have TBI, compared to those without cranial fracture. Specifically, individuals with fracture of the basal region of the cranium are 3.77 times more likely to have co-occurring TBI. Notably, all cases of hinge fractures had associated brain trauma. The data presented in this study can be used for the prediction of the presence of brain trauma, where the presence of cranial fracture is noted.
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    Open Access
    Towards molecular autopsies: Internal validation of the Qubit 1 X dsDNA HS Assay Kit
    (2024) Naidoo, Adele; Abrahams, Shameemah
    Molecular autopsies are post-mortem genetic analyses that can be used to aid in cause of death determination, especially in sudden unexpected death cases. Molecular autopsies involve analysing the decedent's DNA to identify potential pathogenic genetic variants. Accurate quantification of the DNA and associated sequencing libraries is essential, however, no validation studies have been published on the recommended fluorometric quantification methods. The aim of this study was to internally validate the Qubit™ 1X dsDNA HS Assay Kit on the Qubit™ 4 Fluorometer as part of a molecular autopsy workflow for forensic applications. The Qubit™ 1X dsDNA HS Assay workflow was optimised and then used to assess the DNA concentration of control Lambda DNA, extracted DNA from forensic samples and DNA sequencing libraries. The accuracy, precision, dynamic range, and sensitivity were established in accordance with ISO 17025 standards. All parameters met the manufacturer's criteria of acceptance except for the precision of measurements for samples with DNA concentrations ≥ 0.5 ng/µl which were expected to be < 1% CV. The precision of the measurements (1.54% CV – 2.47 % CV), however, was deemed acceptable for our laboratory, as downstream DNA sequencing results surpassed quality thresholds. Additionally, DNA concentration measurements obtained from this DNA quantification workflow were similar to those obtained from other methods that have previously been validated in our laboratory. Overall, the Qubit™ 1X dsDNA HS Assay Kit was considered internally validated for DNA quantification in our laboratory and deemed fit for purpose. This study has enabled the use of this assay in the forensic setting for the first time and has advanced our progression towards implementing a molecular autopsy sequencing workflow in South Africa