Predictive modelling and identification of critical variables of mortality risk in COVID-19 patients.

South Africa was the most affected country in Africa by the coronavirus disease 2019 (COVID-19) pandemic, where over 4 million confirmed cases of COVID-19 and over 102,000 deaths have been recorded since 2019. Aside from clinical methods, artificial intelligence (AI)-based solutions such as machine learning (ML) models have been employed in treating COVID-19 cases. However, limited application of AI for COVID-19 in Africa has been reported in the literature.

Detecting the most critical clinical variables of COVID-19 breakthrough infection in vaccinated persons using machine learning.

Background: COVID-19 vaccines offer different levels of immune protection but do not provide 100% protection. Vaccinated persons with pre-existing comorbidities may be at an increased risk of SARS-CoV-2 breakthrough infection or reinfection. The aim of this study is to identify the critical variables associated with a higher probability of SARS-CoV-2 breakthrough infection using machine learning.

Pathology-supported genetic testing presents opportunities for improved disability outcomes in multiple sclerosis.

Lipid metabolism may impact disability in people with multiple sclerosis (pwMS). Fifty-one pwMS entered an ultrasound and MRI study, of whom 19 had followed a pathology-supported genetic testing program for more than 10 years (pwMS-ON). Genetic variation, blood biochemistry, vascular blood flow velocities, diet and exercise were investigated.

Disability in multiple sclerosis is associated with vascular factors: An ultrasound study.

Background: Although multiple sclerosis (MS) is an immune-related disorder, pharmaceutical interventions targeting the immune system do not stop or reverse disability progression; the major challenge for this condition. Studies show that disability progression in MS is associated with vascular comorbidity and brain volume loss, indicating that a multi-targeted approach is required to prevent debilitation. The aim of the present study was to examine the associations between vascular ultrasound, disability, biochemistry and lifestyle data in people with MS (pwMS).

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part I. Targeting a metabolic model rather than autoimmunity.

In this Review (Part I), we investigate the scientific evidence that multiple sclerosis (MS) is caused by the death of oligodendrocytes, the cells that synthesize myelin, due to a lack of biochemical and nutritional factors involved in mitochondrial energy production in these cells. In MS, damage to the myelin sheaths surrounding nerve axons causes disruption of signal transmission from the brain to peripheral organs, which may lead to disability. However, the extent of disability is not deterred by the use of MS medication, which is based on the autoimmune hypothesis of MS.

-3 long-chain PUFA promote antibacterial and inflammation-resolving effects in -infected C3HeB/FeJ mice, dependent on fatty acid status.

Non-resolving inflammation is characteristic of tuberculosis (TB). Given their inflammation-resolving properties, n-3 long-chain PUFA (n-3 LCPUFA) may support TB treatment. This research aimed to investigate the effects of n-3 LCPUFA on clinical and inflammatory outcomes of Mycobacterium tuberculosis-infected C3HeB/FeJ mice with either normal or low n-3 PUFA status before infection.

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases.

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases.

Identification of an iron-responsive subtype in two children diagnosed with relapsing-remitting multiple sclerosis using whole exome sequencing.

Background: Multiple sclerosis is a disorder related to demyelination of axons. Iron is an essential cofactor in myelin synthesis. Previously, we described two children (males of mixed ancestry) with relapsing-remitting multiple sclerosis (RRMS) where long-term remission was achieved by regular iron supplementation.

Fractional anisotropy of white matter, disability and blood iron parameters in multiple sclerosis.

Unlabelled: Multiple sclerosis (MS) is a disorder related to myelin damage, which can be investigated by neuroimaging techniques such as fractional anisotropy (FA), a measure of microstructural white matter properties. The objectives of this study were to investigate (1) the relationship between FA and disability using an extremes of outcome approach, and (2) whether blood iron parameters were associated with FA and/or disability. Patients diagnosed with MS (n = 107; 14 males and 93 females) had iron parameter tests and disability determinations using the Expanded Disability Status Scale (EDSS).

Efficacy of antipsychotics for irritability and aggression in children: a meta-analysis.

Background: Aggression and irritability in children occur across a range of diagnoses, and are associated with both economic cost and negative psychosocial outcomes. Antipsychotics are frequently prescribed in these cases.

Methods: A random effects meta-analysis of 14 random controlled trials was conducted.

Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway.

Panel-based next generation sequencing (NGS) is currently preferred over whole exome sequencing (WES) for diagnosis of familial breast cancer, due to interpretation challenges caused by variants of uncertain clinical significance (VUS). There is also no consensus on the selection criteria for WES. In this study, a pathology-supported genetic testing (PSGT) approach was used to select two mutation-negative breast cancer patients from the same family for WES.

The adaptor protein Cindr regulates JNK activity to maintain epithelial sheet integrity.

Epithelia are essential barrier tissues that must be appropriately maintained for their correct function. To achieve this a plethora of protein interactions regulate epithelial cell number, structure and adhesion, and differentiation. Here we show that Cindr (the Drosophila Cin85 and Cd2ap ortholog) is required to maintain epithelial integrity.

Multiple sclerosis-like diagnosis as a complication of previously treated malaria in an iron and vitamin D deficient Nigerian patient.

In contrast to malaria, multiple sclerosis (MS) is infrequently found in Black Africans. We describe a 29 year old Nigerian female who developed an MS-like condition with symptoms similar to relapsing-remitting MS following malaria infection, leading to a diagnosis of MS. However, absence of hyperintense lesions in the brain and spinal cord presented a conundrum since not all the diagnostic criteria for MS were met.

Apolipoprotein E genotyping and questionnaire-based assessment of lifestyle risk factors in dyslipidemic patients with a family history of Alzheimer's disease: test development for clinical application.

The cholesterol-raising properties of the apolipoprotein E (APOE) epsilon-4 (ε-4) allele has been validated in the South African population. Mounting evidence supports the added value of APOE genotyping for the evaluation of cardiovascular risk in dyslipidemic patients beyond its established role in the diagnosis of late-onset Alzheimer's disease (AD). The aim of this study was to determine the potential benefits of combining AD family history with questionnaire-based lifestyle assessment to facilitate the clinical interpretation of APOE genotyping results.

Apolipoprotein E ε-4 as a genetic determinant of Alzheimer's disease heterogeneity.

Alzheimer's disease (AD) displays a high degree of heterogeneity in terms of its etiology, presentation, prognosis, and treatment response. This can partly be explained by high-penetrance mutations in the amyloid precursor protein, presenilin 1 and presenilin 2 genes causing amyloid beta aggregation, which is a major pathogenic mechanism in the development of early-onset AD in a small subgroup of patients. Late-onset AD is considered a polygenic disorder in which cumulative risk resulting from interaction with modifiable environmental risk factors may be responsible for the majority of cases.

Clinical relevance of apolipoprotein E genotyping based on a family history of Alzheimer's disease.

Having a family history of Alzheimer' s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -4 (rs429358) in 537 South African individuals participating in a chronic disease screening program, in order to establish whether AD family history modulates the expression of their dyslipidemic effects. Significant differences in the genotype distribution for APOE ε-2 (p=0.

Genomic medicine and risk prediction across the disease spectrum.

Genomic medicine is based on the knowledge that virtually every medical condition, disease susceptibility or response to treatment is caused, regulated or influenced by genes. Genetic testing may therefore add value across the disease spectrum, ranging from single-gene disorders with a Mendelian inheritance pattern to complex multi-factorial diseases. The critical factors for genomic risk prediction are to determine: (1) where the genomic footprint of a particular susceptibility or dysfunction resides within this continuum, and (2) to what extent the genetic determinants are modified by environmental exposures.

Patient-provider communication over social media: perspectives of adolescents with psychiatric illness.

Background: Social media is an increasingly dominant platform for communication, especially among adolescents. Statements from professional bodies and a growing body of empirical evidence support a role for social media in improving provider-patient interactions. In psychiatry, particular concerns exist about the suitability of this style of communication.

A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia.

Background: While antipsychotics are effective in the maintenance treatment of schizophrenia they have safety and tolerability risks. We investigated whether a combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and a metabolic antioxidant, alpha-lipoic acid (α-LA), is effective in preventing relapse after antipsychotic discontinuation in subjects who were successfully treated for 2-3 years after a first-episode of schizophrenia, schizo-affective or schizophreniform disorder.

Methods: In this randomized, double-blind, placebo controlled study antipsychotic treatment was tapered and discontinued and participants received either ω-3 PUFAs (eicosapentaenoic acid 2g/day and docosahexaenoic acid 1g/day)+α-LA 300 mg/day or placebo.

The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors.

Unlabelled: The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene.

Aim: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism.

Pathology-supported genetic testing directed at shared disease pathways for optimized health in later life.

Several chronic, noncommunicable diseases share common genetic risk factors. These include cardiovascular disease and several neurological and psychiatric disorders, as well as some forms of cancer. Clinical compartmentalization and the challenges of translational research have delayed the implementation of personalized medicine.