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Background: Core temperature changes during obstetric spinal anaesthesia are likely underestimated because monitoring is challenging and often not performed. This study aimed to describe the incidence and severity of perioperative hypothermia in patients undergoing caesarean delivery under spinal anaesthesia in a resource-limited setting. Methods: We performed a prospective observational study of parturients undergoing either elective or emergency caesarean delivery under spinal anaesthesia in a South African regional hospital. We used dual-sensor heat flux technology to monitor their core temperature during the perioperative period. The primary outcome was the incidence of clinically relevant hypothermia (defined as core temperature decrease from baseline of > 1 °C) following spinal anaesthesia. Smoothing splines were used to estimate maximum changes in core temperature. Results: We included 166 patients in our analysis. A decrease of > 1 °C occurred in 49% of participants (95% CI 40-63%) while hypothermia (temperature < 36 °C) occurred in 67% (49-78%). Discharge from recovery room with core temperature < 35 °C occurred in 26% (20-34%) of the participants. There was a higher incidence of vomiting in those participants who experienced temperature decreases of > 1 °C (18% vs 6%, p = 0.03). Conclusion: In this resource-constrained environment, clinically relevant hypothermia during obstetric spinal anaesthesia occurred in half of participants. Hypothermia was often severe and participants did not recover by the time of discharge from anaesthesia care. Monitoring of a patient's core temperature should be a standard of care, and further research into the clinical impact of perioperative hypothermia and warming strategies in these settings is warranted. [ABSTRACT FROM AUTHOR]

Abstract Tuberculous meningitis (TBM)—the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture—an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified—1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol—which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Abstract Background The pathogenesis of tuberculous meningitis (TBM) involves infection by Mycobacterium tuberculosis in the meninges and brain. However, recent studies have shown that the immune response and inflammatory processes triggered by TBM can have significant effects on gut microbiota. Disruptions in the gut microbiome have been linked to various systemic consequences, including altered immunity and metabolic dysregulation. Inflammation caused by TBM, antibiotic treatment, and changes in host immunity can all influence the composition of gut microbes. This complex relationship between TBM and the gut microbiome is of great importance in clinical settings. To gain a deeper understanding of the intricate interactions between TBM and the gut microbiome, we report innovative insights into the development of the disease in response to treatment. Ultimately, this could lead to improved outcomes, management strategies and quality of life for individuals affected by TBM. Method We used a targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) approach to investigate metabolites associated with gut metabolism in paediatric participants by analysing the urine samples collected from a control group (n = 40), and an experimental group (n = 35) with confirmed TBM, which were subdivided into TBM stage 1 (n = 8), stage 2 (n = 11) and stage 3 (n = 16). Findings Our metabolomics investigation showed that, of the 78 initially selected compounds of microbiome origin, eight unique urinary metabolites were identified: 2-methylbutyrlglycine, 3-hydroxypropionic acid, 3-methylcrotonylglycine, 4-hydroxyhippuric acid, 5-hydroxyindoleacetic acid, 5-hydroxyhexanoic acid, isobutyrylglycine, and phenylacetylglutamine as urinary markers of dysbiosis in TBM. Conclusion These results – which are supported by previous urinary studies of tuberculosis – highlight the importance of gut metabolism and of identifying corresponding microbial metabolites as novel points for the foundation of improved management of TBM patients.

BackgroundHIV can invade the central nervous system (CNS) early during infection, invading perivascular macrophages and microglia, which, in turn, release viral particles and immune mediators that dysregulate all brain cell types. Consequently, children living with HIV often present with neurodevelopmental delays.MethodsIn this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to analyze the neurometabolic profile of HIV infection using cerebrospinal fluid samples obtained from 17 HIV+ and 50 HIV− South African children.ResultsNine metabolites, including glucose, lactate, glutamine, 1,2-propanediol, acetone, 3-hydroxybutyrate, acetoacetate, 2-hydroxybutyrate, and myo-inositol, showed significant differences when comparing children infected with HIV and those uninfected. These metabolites may be associated with activation of the innate immune response and disruption of neuroenergetics pathways.ConclusionThese results elucidate the neurometabolic state of children infected with HIV, including upregulation of glycolysis, dysregulation of ketone body metabolism, and elevated reactive oxygen species production. Furthermore, we hypothesize that neuroinflammation alters astrocyte–neuron communication, lowering neuronal activity in children infected with HIV, which may contribute to the neurodevelopmental delay often observed in this population.

Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate severe cases of paediatric TBM from controls, through non-invasive urine collection. Urine samples selected for this study were from two paediatric groups. Group 1: controls (n = 44): children without meningitis, no neurological symptoms and from the same geographical region as group 2. Group 2: TBM cases (n = 13): collected from paediatric patients that were admitted to Tygerberg Hospital in South Africa on the suspicion of TBM, mostly severely ill; with a later confirmation of TBM. Untargeted 1H NMR-based metabolomics data of urine were generated, followed by statistical analyses via MetaboAnalyst (v5.0), and the identification of important metabolites. Twenty nine urinary metabolites were identified as characteristic of advanced TBM and categorized in terms of six dysregulated metabolic pathways: 1) upregulated tryptophan catabolism linked to an altered vitamin B metabolism; 2) perturbation of amino acid metabolism; 3) increased energy production–metabolic burst; 4) disrupted gut microbiota metabolism; 5) ketoacidosis; 6) increased nitrogen excretion. We also provide original biological insights into this biosignature of urinary metabolites that can be used to characterize paediatric TBM patients in a South African cohort.

Abstract Background The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease. Methods In this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions. Results HIV/TB co-infection induced significant changes to the host’s lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls. Conclusion This study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.

Most plants have developed unique mechanisms to cope with harsh environmental conditions to compensate for their lack of mobility. A key part of their coping mechanisms is the synthesis of secondary metabolites. In addition to their role in plants’ defense against pathogens, they also possess therapeutic properties against diseases, and their use by humans predates written history. Viruses are a unique class of submicroscopic agents, incapable of independent existence outside a living host. Pathogenic viruses continue to pose a significant threat to global health, leading to innumerable fatalities on a yearly basis. The use of medicinal plants as a natural source of antiviral agents has been widely reported in literature in the past decades. Metabolomics is a powerful research tool for the identification of plant metabolites with antiviral potentials. It can be used to isolate compounds with antiviral capacities in plants and study the biosynthetic pathways involved in viral disease progression. This review discusses the use of medicinal plants as antiviral agents, with a special focus on the metabolomics evidence supporting their efficacy. Suggestions are made for the optimization of various metabolomics methods of characterizing the bioactive compounds in plants and subsequently understanding the mechanisms of their operation.