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Yalka Dayanand,1 Reveshni Pather,1 Nombuso Xulu,1 Irvin Booysen,2 Ntethelelo Sibiya,3 Andile Khathi,1 Phikelelani Ngubane1 1School of Laboratory Medicine and Medical Science, University of Kwazulu-Natal, Durban, South Africa; 2School of Chemistry and Physics, University of Kwazulu-Natal, Pietermaritzburg, South Africa; 3Pharmacology Division, Faculty of Pharmacy, Rhodes University, Grahamstown, South AfricaCorrespondence: Reveshni Pather, Department of Human Physiology School of Laboratory Medicine and Medical Sciences College of Health Sciences, University of KwaZulu-Natal, E-Block, Level 4, University Road, Chiltern Hills, Westville Campus, Private Bag X54001, Westville, Durban, 4000, South Africa, Tel +27826570642, Email reveshnipather1@gmail.comAbstract: The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium’s toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts’ therapeutic and toxic effects, highlight vanadium complexes’ research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver.Keywords: diabetes mellitus, hyperglycaemia, dioxidovanadium, toxicity

Nombuso Xulu,1 Phikelelani Ngubane,1 Andile Khathi,1 Irvin Booysen,2 Ntethelelo Sibiya3 1School of Laboratory Medicine and Medical Sciences, University of KwaZulu Natal, Durban, South Africa; 2School of Chemistry and Physics, College of Agriculture, Engineering and Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa; 3Pharmacology Division, Faculty of Pharmacy, Rhodes University, Grahamstown, South AfricaCorrespondence: Phikelelani NgubaneDepartment of Human Physiology University of KwaZulu Natal, E-Block, Level 4, University Road, Chiltern Hills, Westville Campus, 3629 Private Bag X54001, Westville, Durban, 4000, South AfricaEmail ngubanep1@ukzn.ac.zaBackground: Despite the effective maintenance of glucose homeostasis by insulin in type 1 diabetes mellitus, the drug has been implicated as one of the causes of haematological disturbances, which give rise to cardiovascular complications. As a result, research into alternative therapies for diabetes is needed. In our laboratory, an anti-hyperglycaemic novel vanadium complex has been synthesized using organic heterocyclic ligands. The complex has been shown and improve glycaemic control. The effects of this complex on haematological function, however, have not yet been established. Therefore, this study sought to investigate the haematological effects of dioxidovanadium(V) complex in (STZ)-induced diabetic rats.Methods: Diabetic rats received vanadium complex (40 mg kg − 1 p.o), diabetic untreated (H2O) and insulin treated (0.175 mg kg− 1 s.c), groups acted as a negative and positive control, respectively. Vanadium complex was administered twice daily, and blood glucose concentration was monitored weekly for 5 weeks. Thereafter, the animals were sacrificed followed by blood and kidneys collection for haematological (full blood count and Annexin V), hormonal (EPO) and oxidative status (SOD and GPx) analysis.Results: After 5 weeks, untreated diabetic rats presented with hyperglycaemia compared to non-diabetic rats which was attenuated by vanadium complex administration. Furthermore, vanadium treated groups presented with an augmented RBC count, haematocrit, haemoglobin concentration, MCHC, MCV, and (EPO) levels compared to diabetic control. An increase in annexin V expression hence cell survival was observed in vanadium complex treated rats. Lastly, the administration of the complex improved antioxidant status as evidenced by increases in SOD and GPx concentration in plasma and in the kidneys.Conclusion: The administration of the anti-hyperglycaemic dioxidovanadium(V) complex improved haematological parameters, cell survival and the antioxidant status displayed by the diabetic rats. These results give an indication that the complex might be an effective alternative therapeutic drug for the treatment of hyperglycaemia in DM.Keywords: hyperglycaemia, vanadium complex, haematological, cardiovascular

This article explores and describes primary health care (PHC) post-basic nursing students' experiences during clinical placements so as to address the challenges that are faced within the clinical settings. Work integrated learning (WIL), like in any other nursing course, is essential in PHC education as required by the South African Nursing Council (SANC). In the clinical setting, students develop clinical skills which they will need as qualified PHC practitioners. This is achieved through instruction and guidance by lecturers, mentors and clinical staff. However, the clinical learning environment can confront students with many challenges. During a qualitative study, purposive sampling selected nine students registered for Clinical Nursing Science, Health Assessment, Treatment and Care at a university. Students were placed in the clinical settings of Health Districts A and B in KwaZulu-Natal, South Africa. In-depth interviews were conducted and the following five themes emerged during data analysis: shortage of staff; inadequate material/non-human resources; lack of supervision in the clinical facilities; distant clinical facilities; and insufficient practice in the clinical skills laboratory. These themes related to the challenges that students experience while engaged in their WIL placement. [ABSTRACT FROM AUTHOR]

Cervical cancer is a significant problem in KwaZulu-Natal, South Africa. However, the implementation of the provincial cervical screening programme has been slow. Registered nurses need to be knowledgeable about the disease and comply with the screening programme. The purpose of this study was to determine the perceptions of registered nurses in the public sector primary health care clinics in KwaZulu-Natal, regarding the cervical screening programme, problems experienced and their compliance with the criteria for selecting clients for screening. An exploratory, descriptive and qualitative design was used. The sample consisted of all consenting registered nurses from the selected clinics (n = 21), who participated in focus group discussions. Data were analysed using thematic content analysis. Although appreciative of the screening programme, the nurses disagreed with the starting age of 30 and 10 year intervals for Pap smears, believing that younger women are at risk due to HIV and AIDS and sexually transmitted infections. Further education of registered nurses should ensure that they understand the natural course of the disease and the rationale for the guideline policy. [ABSTRACT FROM AUTHOR]

Employing a capping agent during the synthesis of nanoparticles has been reported to play a role in controlling size and shape of the nanoparticles. Due to this reason, this study reports the synthesis of silver selenide nanoparticles using different environmentally friendly capping agents (green tea, glucose, ascorbic acid and chitosan) in order to investigate their effect on the size and shape of the nanoparticles. Transmission electron microscopy (TEM) results showed that the nanoparticles have different shapes (rods, spheres and cubes) with an average size of 8–96 nm depending on the capping agent used. Fourier transformer infrared (FTIR) spectroscopy confirmed that the capping of nanoparticles was successful, while X-ray diffraction (XRD) showed that the nanoparticles have an orthorhombic phase.

Background: Prediabetes (PD) is associated with intermediate hyperglycaemia, dyslipidaemia, reduced nitric oxide (NO) bioavailability and moderate hypertension. All these factors are risk factor for preeclampsia (PE). However, the effects of the PD on placental function have not been shown. Accordingly, this study sought to investigate a possible link between maternal PD and the risk of developing PE., Methods: Pregnant female Sprague-Dawley rats ( N  = 18) were divided into normal, preeclamptic and prediabetic groups ( n  = 6 in each group) to study the effects of maternal PD on placenta function over the period of 19 days. Blood glucose and blood pressure were measured on gestational day (GND) 0, 9 and 18. Placental vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) mRNA expression were measured terminally. Data were analysed using ANOVA followed by the Tukey-Kramer post hoc test. Values of p  < .05 were used to indicate statistical significance., Results: Maternal PD and PE significantly increased blood glucose, decrease NO concentration and increase in MAP by comparison to the normal pregnant control group. Maternal PD significantly decreased VEGF, PlGF mRNA expression with a slight increase in sFlt-1 mRNA expression comparison to the normal pregnant control group., Conclusions: Maternal PD is associated with placental dysfunction due to impaired glucose handling, endothelial dysfunction and an imbalance in angiogenic and antiangiogenic factors. Therefore, maternal PD is a risk factor of PE.

Efavirenz, tenofovir, rifampicin, simvastatin, lamotrigine and clarithromycin are known potential mitochondrial toxicants. Mitochondrial toxicity has been reported to disrupt the chain of events in the insulin signalling pathway. Considering the upward trajectory of diabetes mellitus prevalence, studies which seek to uncover probable risk factors for developing diabetes should be encouraged. This study aimed to evaluate the intracellular mechanisms leading to the development of insulin resistance in the presence of various conventional pharmacological agents reported as potential mitochondrial toxicants in skeletal muscle cell line. Differentiated C2C12 preparations were exposed to multiple concentrations of efavirenz, tenofovir, rifampicin, simvastatin, lamotrigine, and clarithromycin, separately. Glucose handling was evaluated by observing the changes in insulin-stimulated glucose uptake and assessing the changes in GLUT4 translocation, GLUT4 expression and Akt expression. The changes in mitochondrial function were evaluated by assessing mitochondrial membrane integrity, cellular ATP production, generation of intracellular reactive oxygen species, expression of tafazzin and quantification of medium malonaldehyde. Insulin stimulated glucose uptake was perturbed in C2C12 pre-treated with potential mitotoxicants. Additionally, ATP synthesis, alterations in mitochondrial membrane potential, excessive accumulation of ROS and malonaldehyde were observed in the presence of potential mitotoxicants. Particularly, we observed suppression of proteins involved in the insulin signalling pathway and maintenance of mitochondrial function namely GLUT4, Akt and tafazzin. Mitochondrial toxicants can potentially induce insulin resistance emanating from mitochondrial dysfunction. These new findings will contribute to the understanding of underlying mechanisms involved in the development of insulin resistance linked to mitochondrial dysfunction., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Kuretu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite evidence demonstrating the risks of developing diabetes mellitus because of SARS-CoV-2, there is, however, insufficient scientific data available to elucidate the relationship between diabetes mellitus and COVID-19. Research indicates that SARS-CoV-2 infection is associated with persistent damage to organ systems due to the systemic inflammatory response. Since COVID-19 is known to induce these conditions, further investigation is necessary to fully understand its long-term effects on human health. Consequently, it is essential to consider the effect of the COVID-19 pandemic when predicting the prevalence of diabetes mellitus in the future, especially since the incidence of diabetes mellitus was already on the rise before the pandemic. Additional research is required to fully comprehend the impact of SARS-CoV-2 infection on glucose tolerance and insulin sensitivity. Therefore, this article delves deeper into the current literature and links the perceived relationship between SARS-CoV-2 and diabetes. In addition, the article highlights the necessity for further research to fully grasp the mechanisms that SARS-CoV-2 utilises to induce new-onset diabetes. Where understanding and consensus are reached, therapeutic interventions to prevent the onset of diabetes could be proposed. Lastly, we propose advocating for the regular screening of diabetes and pre-diabetes, particularly for the high-risk population with a history of COVID-19 infection.

In light of the expected increase in the prevalence of diabetes mellitus due to an aging population, sedentary lifestyles, an increase in obesity, and unhealthy diets, there is a need to identify potential pharmacological agents that can heighten the risk of developing diabetes. Similarly, it is equally important to also identify those agents that show blood glucose-lowering properties. Amongst these agents are tyrosine kinase inhibitors used to treat certain types of cancers. Over the last two decades, there has been an increase in the use of targeted chemotherapy for cancers such as renal cell carcinoma, chronic leukaemia, and gastrointestinal stromal tumours. Small molecule tyrosine kinase inhibitors have been at the forefront of targeted chemotherapy. Studies have shown that small molecule tyrosine kinase inhibitors can alter glycaemic control and glucose metabolism, with some demonstrating hypoglycaemic activities whilst others showing hyperglycaemic properties. The mechanism by which small molecule tyrosine kinase inhibitors cause glycaemic dysregulation is not well understood, therefore, the clinical significance of these chemotherapeutic agents on glucose handling is also poorly documented. In this review, the effort is directed at mapping mechanistic insights into the effect of various small molecule tyrosine kinase inhibitors on glycaemic dysregulation envisaged to provide a deeper understanding of these chemotherapeutic agents on glucose metabolism. Small molecule tyrosine kinase inhibitors may elicit these observed glycaemic effects through preservation of β-cell function, improving insulin sensitivity and insulin secretion. These compounds bind to a spectrum of receptors and proteins implicated in glucose regulation for example, non-receptor tyrosine kinase SRC and ABL. Then receptor tyrosine kinase EGFR, PDGFR, and FGFR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mugiya, Mothibe, Khathi, Ngubane and Sibiya.)

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Khumalo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mitochondrial impairment has been associated with the development of insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM). However, the relationship between mitochondrial impairment and insulin resistance is not fully elucidated due to insufficient evidence to support the hypothesis. Insulin resistance and insulin deficiency are both characterised by excessive production of reactive oxygen species and mitochondrial coupling. Compelling evidence states that improving the function of the mitochondria may provide a positive therapeutic tool for improving insulin sensitivity. There has been a rapid increase in reports of the toxic effects of drugs and pollutants on the mitochondria in recent decades, interestingly correlating with an increase in insulin resistance prevalence. A variety of drug classes have been reported to potentially induce toxicity in the mitochondria leading to skeletal muscle, liver, central nervous system, and kidney injury. With the increase in diabetes prevalence and mitochondrial toxicity, it is therefore imperative to understand how mitochondrial toxicological agents can potentially compromise insulin sensitivity. This review article aims to explore and summarise the correlation between potential mitochondrial dysfunction caused by selected pharmacological agents and its effect on insulin signalling and glucose handling. Additionally, this review highlights the necessity for further studies aimed to understand drug-induced mitochondrial toxicity and the development of insulin resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kuretu, Arineitwe, Mothibe, Ngubane, Khathi and Sibiya.)

Diabetes mellitus (DM) and related complications continue to exert a significant burden on health care systems globally. Although conventional pharmacological therapies are beneficial in the management of this metabolic condition, it is still necessary to seek novel potential molecules for its management. On this basis, we have synthesised and evaluated the anti-diabetic properties of four novel thiazolidinedione (TZD)-derivatives. The TZD derivatives were synthesised through the pharmacophore hybridisation strategy based on N -arylpyrrole and TZD. The resultant derivatives at different concentrations were screened against key enzymes of glucose metabolism and glucose utilisation in the liver (HEP-G2) cell line. Additionally, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. Docking of these molecules against PPAR-γ predicted strong binding, similar to that of rosiglitazone. Hence, TZDD2 was able to increase glucose uptake in the liver cells as compared to the control. The enzymatic inhibition assays showed a relative inhibition activity; with all four derivatives exhibiting ≥ 50% inhibition activity in the α-amylase inhibition assay and a concentration dependent activity in the α-glucosidase inhibition assay. All four derivatives exhibited ≥30% inhibition in the aldose reductase inhibition assay, except TZDD1 at 10 µg/mL. Interestingly, TZDD3 showed a decreasing inhibition activity. In the dipeptidyl peptidase-4 inhibition assay, TZDD2 and TZDD4 exhibited ≥20% inhibition activity.

Background: Diabetes mellitus and prediabetes have been shown to be associated with high rates of developing severe COVID 19 complications resulting in morbidity and mortality. Emerging reports suggest that COVID 19 is associated with glycaemic control aberrations, although the extent is not clear at present. Accordingly, in this review, the efforts are directed to shed light on why we can anticipate an increase in diabetes cases amid or post-COVID 19 pandemic., Methods: Articles reviewed were identified using the Google Scholar database, and the search was done using the English language., Results: Previous studies have shown that viral inflammation triggers insulin resistance, which can progress to overt diabetes. SARS-CoV-2 has also been shown to cause acute pancreatitis, which can increase the risk of developing diabetes mellitus. The control of the COVID 19 pandemic partly relied on non-pharmaceutical measures, which included lockdowns. This resulted in a lack of physical activity and unhealthy eating behaviour, which could contribute to obesity and, ultimately, insulin resistance., Conclusion: While no concrete data has been established on the possibility of seeing an increase in diabetes prevalence due to COVID 19, studies are necessary to establish the link. Despite the unavailability of data at present, we suggest that frequent screening of diabetes and prediabetes should be encouraged, especially in those individuals with a history of COVID 19 infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nalidixic acid is a synthetic antibiotic discovered in the 1960s during the synthesis of chloroquine, an effective drug for treating malaria. Nalidixic acid became the backbone for developing quinolones that are now widely used clinically for the treatment of various bacterial infections. The mechanism of action of quinolone involves the inhibition of topoisomerase II and topoisomerase IV. In attempts to improve the potency of fluoroquinolones, modifications were made; these modifications resulted in the emergence of newer generations of fluoroquinolones. Also, due to these modifications, several side effects were noted, including blood glucose control aberrations. Among fluoroquinolones that disrupt glucose homeostasis is gatifloxacin, which is in the third-generation category. Fluoroquinolones have been demonstrated to induce glycaemic aberrations by enhancing pancreatic cells' insulin secretion and interaction with antidiabetic agents via inhibition of cytochrome P450 enzymes. Considering their ability to induce hypoglycaemia, few studies have reported repurposing of quinolones as antidiabetic agents. Hyperglycaemia has also been reported to often precede hypoglycaemia. Due to the ability to decrease blood glucose, it is not surprising that some authors have reported novel quinolone derivates with antidiabetic properties in experimental studies. However, there is still a paucity of data regarding the effect of quinolones derivatives on glycaemic control. Understanding how fluoroquinolones lower blood glucose concentration could serve as the basis for developing novel quinolone derivatives with the sole purpose of lowering blood glucose concentrations. Although there are various conventional anti-hyperglycaemic agents, due to their associated shortfalls as well as an increase in the prevalence of diabetes, the discovery and development of new antidiabetics are warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Since the discovery of insulin, continuous developments of this peptide have led to better management of diabetes mellitus, thus leading to a decrease in diabetes-related mortality. Despite these developments, we have seen an increase in diabetes cases, which has further necessitated more innovative methods for diabetes management. The subcutaneous administration of insulin remains the mainstay therapy for type 1 diabetes mellitus. However, despite the availability of insulin analogues with improved pharmacokinetics, challenges with conventional administration exist. The challenges associated with insulin injections include hypoglycaemic episodes, needle phobia, and injection-site inflammation, which all have been reported to reduce patient compliance. Ongoing research on diabetes management strives to develop therapies that provide improved glycaemic control with minimal side effects. In part, for these reasons, we have seen an increase in the search and development of alternative insulin delivery systems that are envisaged to circumvent the shortfalls associated with the conventional administration route. Several alternative drug delivery systems, such as oral, pulmonary, buccal, nasal, and transdermal, have been explored in the last century. These efforts have not been without victory, as we have seen the emergence of pulmonary (Exubera and Afrezza) and buccal insulin delivery systems licenced for therapeutic use. Despite the success seen in these two systems, their marketability and popularity have been severely compromised due to reported safety concerns. Although oral insulin delivery has always shown promise in the past decades; however, it was only limited to preclinical trials. The main challenge associated with this delivery route is poor bioavailability, which necessitates high insulin concentration to be administered. Due to recent developments, oral insulin has reached phase 3 clinical trials. It is believed that patients would prefer oral insulin as their preference is often observed for oral antidiabetics over injected ones. In the last decade, transdermal insulin has also gained interest, where delivery of insulin with a concomitant reduction in blood glucose concentration has been demonstrated in vivo. However, at present, there are no clinical studies that have reported the efficacy of transdermal insulin administration. With technological advancement, there is a potential to develop yet another insulin delivery system that would likely enter the markets. As these novel delivery systems have been found to be effective, emerging competing products should be welcome and appreciated., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Mycobacterium tuberculosis bloodstream infection is a leading cause of death in people living with HIV and disseminated bacillary load might be a key driver of disease severity. We aimed to assess Xpert MTB/RIF Ultra (Xpert Ultra) testing of blood as a diagnostic for M tuberculosis bloodstream infection and investigate cycle threshold as a quantitative disease biomarker., Methods: In this cohort study, we obtained biobanked blood samples from a large and well characterised cohort of adult patients admitted to hospital in Western Cape, South Africa with suspected HIV-associated tuberculosis and a CD4 count less than 350 cells per μL. Patients already receiving antituberculosis therapy were excluded. Samples were obtained on recruitment within 72 h of admission to hospital, and patients were followed up for 12 weeks to determine survival. We tested the biobanked blood samples using the Xpert Ultra platform after lysis and wash processing of the blood. We assessed diagnostic yield (proportion of cases detected, with unavailable test results coded as negative) against a microbiological reference, both as a function of markers of critical-illness and compared with other rapid diagnostics (urine lipoarabinomannan and sputum Xpert). Quantitative blood Xpert Ultra results were evaluated as a disease biomarker by assessing association with disease phenotype defined by principal component analysis of 32 host-response markers. Prognostic value compared to other tuberculosis biomarkers was assessed using likelihood ratio testing of nested models predicting 12-week mortality., Findings: Between Jan 16, 2014, and Oct 19, 2016, of the 659 participants recruited to the parent study, 582 had an available biobanked blood sample. 447 (77%) of 582 met the microbiological reference standard for tuberculosis diagnosis. Median CD4 count was 62 (IQR 221-33) cells per μL, and 123 (21%) of participants died by 12-weeks follow-up. Blood Xpert Ultra was positive in 165 (37%) of 447 participants with confirmed tuberculosis by the microbiological reference standard, with a diagnostic yield of 0·37 (95% CI 0·32-0·42). Diagnostic yield increased with lower CD4 count or haemoglobin, and outperformed urine lipoarabinomannan testing in participants with elevated venous lactate. Quantitative blood Xpert Ultra results were more closely associated with mortality than other tuberculosis biomarkers including blood culture, and urine lipoarabinomannan, or urine Xpert (all p<0·05). A principal component of clinical phenotype capturing markers of inflammation, tissue damage, and organ dysfunction was strongly associated with both blood Xpert-Ultra positivity (associated with a SD increase of 1·1 in PC score, p<0·0001) and cycle threshold (r= -0·5; p<0·0001)., Interpretation: Xpert Ultra testing of pre-processed blood could be used as a rapid diagnostic test in critically ill patients with suspected HIV-associated tuberculosis, while also giving additional prognostic information compared with other available markers. A dose-response relationship between quantitative blood Xpert Ultra results, host-response phenotype, and mortality risk adds to evidence that suggests M tuberculosis bloodstream infection bacillary load is causally related to outcomes., Funding: Wellcome Trust, National Institute of Health Fogarty International Center, South African MRC, UK National Institute of Health Research, National Research Foundation of South Africa., Translations: For the Xhosa and Afrikaans translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Vanadium has demonstrated antihyperglycemic effects in diabetes mellitus (DM) but is, however, associated with toxicity. Therefore, new vanadium complexes envisaged to possess heightened therapeutic potency while rendering less toxicity are being explored. Accordingly, the aim of the study was to investigate the effects of a dioxidovanadium (V) complex, cis-[VO2 (obz) py], on selected glucose metabolism markers in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were treated orally with cis-[VO2 (obz) py] (10, 20, and 40 mg/kg) twice every 3rd day for 5 weeks. Blood glucose concentrations, body weight, and food and water intake were monitored weekly, for 5 weeks. Rats were then euthanized after which blood, liver, and muscle tissues were collected for biochemical analysis. The administration of dioxidovanadium complex significantly decreased blood glucose concentrations throughout the 5-week period in comparison with the diabetic control (DC). The attenuation of hyperglycemia was accompanied by an increased glycogen concentration in both liver and muscle tissues in the treated groups. Furthermore, a significant increase was observed in the expression of glucose transporter type 4 (GLUT4) in the skeletal muscle tissues and glycogen synthase in the liver tissues. These findings indicate that our vanadium complex cis-[VO2 (obz) py] may exert antihyperglycemic effects through increased glucose uptake, glycogen synthesis, and increased GLUT4 and glycogen synthase expression., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Bonisiwe Mbatha et al.)

Diabetes mellitus has been identified as a major risk factor for developing severe COVID 19 complications. In this review article, the efforts were directed to provide insights and the possible extent to which some diabetic pharmacological interventions may exacerbate COVID 19 or may not be idyllic options for COVID 19 patients. Articles reviewed were identified using the Google scholar database, and search was done using the English language. Anti-hyperglycemic is associated with undesirable effects including episodes of hypoglycemia, diarrhea, lactic acidosis, and increased risks of cardiovascular and hepatic hazards. These undesirable effects associated with the anti-hyperglycemic agents possess a threat of developing severe COVID19 complications Therefore, this calls for more studies to understand the extent of the risks these agents possess in diabetic COVID 19 patients. Almost all the anti-hyperglycemic agents have the potential to worsen COVID 19, despite their class. COVID 19 may limit the options in terms of available anti-hyperglycemic agents which may not heighten the risk of developing severe COVID 19 complications. The research towards the discovery and development of new compounds and also new therapeutic targets for hyperglycemia should be encouraged and welcome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Malaria remains a public health problem decimating vulnerable populace especially in resource-constrained areas in Zimbabwe. Significant progress towards malaria elimination has beenik made in the previous decades through intensified and improved malaria control measures such as indoor residual spraying (IRS), distribution of long-lasting insecticidal nets (LLIN), artemisinin-based combination therapy and administration of intermittent preventive treatment in pregnancy. However, the outbreak of pandemics like coronavirus disease (COVID-19), cyclones and tropical storms, lack of funding, porous political environment, dearth of resources for vector control, changes in vector behaviour, vector resistance to insecticides, community behavioural change and lack of feasible and sustainable digital technologies for managing malaria control interventions retards progress made towards malaria elimination. Also, arbitrary political environment and unstable economic situation often interfere with health programmes which subsequently lead to malaria outbreaks. Most recently, the country recorded a sharp increase in malaria incidences in malaria-endemic areas especially during the pandemic due to some factors such as movement restrictions, temporary cancellation of IRS activities, delayed delivery of IRS chemicals and recursive lockdown. Therefore, we propose ways to mitigate future malaria outbreaks and advocate for reconsidering malaria elimination strategies to addresses emerging challenges in eradicating malaria in Zimbabwe., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Despite the success of antidiabetic drugs in alleviation of hyperglycaemia, diabetic complications, including renal dysfunction, continue to be a burden. This raises the need to seek alternative therapies that will alleviate these complications. Accordingly, the aim of this study was to investigate the effects of dioxidovanadium(V) complex cis -[VO 2 (obz)py] on renal function in diabetic rats. Streptozotocin-induced diabetic rats were treated with cis -[VO 2 (obz)py] (40 mg·kg -1 ) twice every third day for five weeks. Diabetic untreated and insulin-treated rats served as the diabetic control and positive control, respectively. Blood glucose concentrations, water intake, urinary output, and mean arterial pressure (MAP) were monitored weekly for five weeks. Rats were then euthanized, and blood and kidney tissues were collected for biochemical analysis. Significant decreases in blood glucose concentrations, MAP, glomerular filtration rate (GFR), and SGLT2 expression, as well as plasma angiotensin and aldosterone concentrations, were observed in the treated groups compared with the diabetic control. The complex also increased urinary glucose concentrations, antioxidant enzymes GPx and SOD concentrations, and decreased MDA concentrations and kidney injury molecule (KIM-1) concentrations. These findings suggest that the anti-hyperglycaemic effects of this vanadium complex may ameliorate kidney dysfunction in diabetes.

Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus (DM). Despite the anti-hyperglycemic effects of various anti-diabetic therapeutic agents like insulin, some of these drugs are implicated in precipitating cardiovascular dysfunction. There is therefore an imperative need to seek alternative drugs that may ameliorate these complications. Accordingly, the aim of the study was to investigate the effects of a dioxidovanadium (V) complex, cis-[VO 2 (obz)py]) on selected cardiovascular function markers in STZ-induced diabetic rats. The vanadium complex (40 mg kg) was administered orally twice every 3rd day 5 weeks, non-diabetic and diabetic control groups received distilled water whereas the insulin group received subcutaneous insulin injections twice daily for 5 weeks. Blood glucose concentrations, mean arterial pressure (MAP), heart rate, triglycerides (TG) and total cholesterol concentrations were monitored weekly for 5 weeks. Rats were then euthanised and blood and hearts were collected for biochemical analysis. There was a significant decrease in blood glucose, triglycerides, cholesterol concentrations as well as blood pressure of vanadium treated rats compared to the untreated diabetic animals. Vanadium treatment also attenuated cardiac oxidative stress and decreased the expression of transforming growth factor β1 (TGFβ1) and Smad7. Lastly, the administration of the vanadium complex significantly decreased C reactive protein (CRP) and cardiotropin 1(CT-1) concentrations in the plasma and heart tissues. The administration of the dioxidovanadium(V) complex to diabetic rats culminated into cardio-protective effects. Taken together, these observations suggest that this metal complex exhibit a significant potential as an alternative therapeutic drug for DM management.

In this study, three coagulants (ferromagnetite (F), alum (A), and eggshells (E)) and their hybrids (FA, FE, and FEA) were investigated as possible cost-effective coagulants for the treatment of industrial wastewater. Scanning electron microscopy (SEM) coupled with energy-dispersive X-ray (EDX) was used to characterize the morphological and elemental compositions of the coagulants. The effects of coagulant dosage (10-60 mg/L) and settling time were investigated for the removal of turbidity, color, and total suspended solids. A jar tester (JTL6) operating at conditions of 150 rpm for 2 min (rapid mixing) and 30 rpm for 15 min (slow mixing) was employed. Results from the characterized supernatant showed about 80% removal of the contaminants. The prospects of F were proven to be the most effective as compared to the binary (FA > FE) and the ternary hybridized (FEA) coagulants. At an optimum dosage and settling time of 20 mg/L and 30 min, respectively, the treatability performance of F was clearly proven to be viable for wastewater treatment.

Background: Altered function of the hypothalamic-pituitary-adrenal (HPA) axis in type 2 diabetic patients, a condition preceded by pre-diabetes, has been shown to increase the risk of depression as well as cause downstream effects resulting in upregulation of gluconeogenesis and dyslipidemia. In addition, stress, either psychological from managing diabetes or lifestyle related, further activates the HPA axis causing an exaggerated stress response. This study investigated the activity of the HPA axis in selected markers of glucose handling, and the stress response relative to components of the HPA axis in a diet-induced pre-diabetic rat model., Methods: Sprague Dawley Rats were randomly divided into non-pre-diabetic group (NPD) and pre-diabetic group (PD) (n = 6, per group) over a 20-week induction period and a further 12-week experimental period to get 32 weeks. At the end of the 20 and 32-week periods, glucose handling using the Homeostasis Model Assessment indices, adrenocorticotropic (ACTH) and corticosterone (CORT) concentrations were measured. Stress was induced and the forced swim test were performed in the 12-week experimental week. At the end of 32 weeks glucocorticoid and mineralocorticoid hippocampal receptors were also measured., Results: Impaired glucose handling in the PD group as well as increase in corticosterone was observed at the end of both 20 and 32-week periods by comparison to NPD groups. No changes were observed in ACTH concentration at week 20 while, at week 32, a decrease in plasma ACTH concentration was observed in the PD group by comparison to the NPD group. The stressed-induced animals were stressed using the forced swim test: the behaviour observed showed an increase in immobility time in the PD stressed group by comparison to the NPD group. This was followed by the observation of a decrease in ACTH and CORT concentration in the PD stressed group by comparison to the NPD stressed group. Mineralocorticoid and glucocorticoid receptors gene expression were elevated in the stressed PD group relative to the stressed NPD group., Conclusion: These observations, together, suggest that diet-induced pre-diabetes is associated with impaired HPA axis activity and deteriorating response to stress.

Diabetics are susceptible to hepatic dysfunction risks due to hyperglycaemia and insulin therapy. Conventional diabetes treatments improve glycaemic control; however, hepatic hazards associated with these agents remains a challenge. Accordingly, this study sought to investigate the effect of a dioxidovanadium complex (V) on the hepatic function in streptozotocin-induced diabetic rats. Sprague-Dawley rats (240-250 g) were divided into 4 groups ( n = 6): nondiabetic control, diabetic control, insulin-treated, and vanadium complex groups. The dioxidovanadium (10, 20, and 40 mg/kg) was administered twice every 2nd day for 5 weeks and blood glucose concentration was monitored weekly. At the end of the experimental period, all the experimental groups were sacrificed, and then the lipid profile, liver superoxide dismutase, glutathione peroxidase and malondialdehyde, plasma alanine aminotransferase and aspartate aminotransferase, and C-reactive protein (CRP) concentration were measured. The administration of dioxidovanadium significantly alleviated hyperglycaemia with concomitant attenuation in oxidative stress as evidenced by reduced malondialdehyde concentrations. Furthermore, vanadium complex abolished diabetes-induced dyslipidaemia. Lastly, vanadium complex administration attenuated the increase in alanine aminotransferase, aspartate aminotransferase, and plasma C-reactive protein. These findings suggest that this metallo-compound (dioxidovanadium) may ameliorate liver dysfunction often observed in diabetes.

Background: Chronic hyperglycaemia-induced haematological changes increase the risk of cardiovascular complications in diabetic patients. The administration of insulin injection as a bolus is accompanied with increased blood viscosity, which is not recommended for patients with congestive heart failure. Momordica balsamina methanolic extract (MB) has previously been shown to possess anti-hyperglycaemic and renal dysfunction ameliorative effects; however, the haematological effects of MB have not been shown. The current study therefore, investigated the short-term effects MB on selected haematological parameters in streptozotocin (STZ)-induced diabetic rats., Methods: Briefly, the air-dried Momordica balsamina leaves were sequentially extracted with methanol to yield a methanolic extract. STZ-induced diabetic rats were divided into untreated and treated groups with insulin (170 μg kg -1 s.c.) and metformin (500 mg kg -1 p.o.) MB (250 mg kg -1 p.o.). MB was administered twice daily for the 5-week experimental period. Blood glucose concentration was monitored weekly. Animals were sacrificed terminally. Blood and kidneys were collected for haematological and biochemical analysis respectively., Results: Treatment with MB significantly decreased blood glucose concentration and improved erythropoietin secretion, thus significantly increasing red blood cell production in treated diabetic animals by comparison to untreated animals. MB also significantly improved haemoglobin concentrations and moderately increased erythrocyte indices specifically, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) and mean corpuscular haemoglobin (MCH) to no significance by comparison to untreated diabetic animals. MB treatment decreased the oxidative stress evoked by the induction of diabetes while improving the antioxidant status of treated animals by comparison to untreated animals respectively., Conclusions: Administration of Momordica balsamina methanolic extract protects against some injurious haematological changes induced by hyperglycaemia, which may reduce the risks of cardiovascular complications., (Copyright © 2019. Published by Elsevier Masson SAS.)

Peripheral neuropathic condition is amongst the classical symptoms of progressed diabetes. An intensive glycemic control with insulin injections has been shown to delay the onset and the progression of this condition in diabetes. In this study, we investigated the effect of pectin-insulin patch application on peripheral neuropathic symptoms in streptozotocin-induced diabetic rats. Pectin-insulin patches (20.0, 40.8, and 82.9 μg/kg) were daily applied thrice in streptozotocin-induced diabetic rats for 45 days. The diabetic animals sham treated with insulin-free patch served as negative control, while diabetic animals receiving subcutaneous insulin served as positive controls. The locomotor activity, gripping strength, and thermal perception were assessed at day 36, day 40, and day 44, respectively. On the 45th day, the animals were sacrificed, after which the plasma insulin, nitric oxide, C-reactive protein, tumor necrosis factor alpha, and malondialdehyde were measured. The patch application attenuated hyperglycemia with an improvement in the locomotor activity, thermal perception, and gripping strength in diabetic animals. Furthermore, the application of the patch augmented plasma nitric oxide while attenuating plasma malondialdehyde and tumor necrosis factor alpha. The application of pectin-insulin patch delays the onset of peripheral neuropathic-like symptoms in diabetic animals.

Background: Studies suggest that Momordica balsamina ( intshungu ) possesses hypoglycaemic effects. The effects of Momordica balsamina on diabetic complications such as DN, however, have not been established. Accordingly, this study seeks to investigate the effects of M. balsamina on kidney function in STZ-induced diabetic rats., Methods: Methanolic extracts (ME) of M. balsamina 's leaves were used in this study. Short-term effects of M. balsamina methanolic extract on kidney function and MAP were studied in STZ-induced diabetic rats treated twice daily with M. balsamina methanolic extract (250 mg/kg), insulin (175  μ g/kg, s.c.), and metformin (500 mg/kg) for 5 weeks., Results: M. balsamina methanolic extract significantly increased Na + excretion outputs in STZ-induced diabetic rats by comparison to STZ-diabetic control rats. M. balsamina methanolic extract significantly increased GFR in STZ-diabetic rats with a concomitant decrease in creatinine concentration and also reduced kidney-to-body ratio, albumin excretion rate (AER), and albumin creatinine ratio (ACR). M. balsamina methanolic extract significantly reduced MAP in STZ-diabetic animals by comparison with STZ-diabetic control animals. These results suggest that M. balsamina methanolic extract not only lowers blood glucose but also has beneficial effects on kidney function and blood pressure., Conclusion: These findings suggest that M. balsamina may have beneficial effects on some processes that are associated with renal derangement in STZ-induced diabetic rats.

Background: Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus. Despite the beneficial effects of subcutaneous insulin, reports suggest that the therapy itself precipitates cardiovascular risks due to the high insulin concentration administered. It is therefore necessary to seek alternative routes of insulin administration that may bypass the undesirable effects associated with high plasma insulin concentrations. Accordingly, the present study investigated the effects of a novel transdermal pectin-insulin patch on selected markers of cardiovascular function in diabetes., Methods: Pectin-insulin matrix patches (20.0, 40.8, and 82.9 μg/kg) were prepared as described previously. The three formulations were applied to streptozotocin-induced diabetic rats thrice daily. Blood glucose concentrations and mean arterial pressure (MAP) were monitored weekly for 5 weeks. Rats were then killed and blood collected for analysis of the lipid profile, cardiotropin-1, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP)., Results: The patches decreased blood glucose concentrations and diabetes-induced disturbances in lipid profile were attenuated by patch application (82.9 μg/kg). The diabetes-induced increase in MAP was also attenuated in patch (82.9 μg/kg)-treated rats. Patch treatment resulted in a decreased heart weight: body weight ratio, as well as reductions in cardiotropin-1, TNF-α, and hsCRP concentrations., Conclusions: Application of the pectin-insulin patch protects against the debilitating cardiovascular effects associated with conventional diabetes treatment. This suggests that the pectin-insulin patch may provide an effective alternative therapeutic approach to the commonly used subcutaneous insulin injections in the management of diabetes., (© 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background/aims: Renal damage and dysfunction is attributed to sustained hyperglycaemia in overt diabetes. Subcutaneous insulin injections are beneficial in delaying the progression of renal dysfunction and damage in diabetics. However, the current mode of administration is associated with severe undesirable effects. In this study, we evaluated the ameliorative effects of pectin-insulin dermal patches on renal dysfunction in diabetes., Methods: Pectin-insulin patches (20.0, 40.8 and 82.9 µg/kg) were applied on the skin of streptozotocin-induced diabetic rats, thrice daily for 5 weeks. Blood glucose concentration, blood pressure and urine output volume were recorded on week 5 after which the animals were sacrificed after which the kidneys and plasma were collected. Kidney nephrin expression and urinary nephrin concentration, albumin excretion rate (AER), creatinine clearance (CC) and albumin creatinine ratio (ACR) were assessed., Results: Patch application resulted in reduced blood glucose concentration and blood pressure. Furthermore, pectin-insulin patch treatment resulted in increased kidney nephrin expression and reduced urinary nephrin concentration. AER, CC ACR were also reduced post patch application., Conclusions: The application of pectin-insulin patch limited diabetes associated kidney damaged and improved kidney function. These observations suggest that pectin-insulin patches may ameliorate kidney dysfunction that is associated with chronic subcutaneous insulin administration., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background: Basic Antenatal Care (BANC) is an approach that is used in the public health institutions of South Africa to provide health care services to pregnant women. The approach was introduced as a quality improvement strategy based on the belief that good quality Antenatal Care (ANC) could reduce maternal and perinatal mortalities and improve maternal health., Aim: The aim of this study was to analyse pregnant women's ANC records for evidence suggesting that the BANC principles of good care and guidelines were being applied., Setting: The study was conducted in the 12 primary health care clinics that were providing ANC services using the BANC approach in eThekwini district, KwaZulu-Natal., Methods: A cross-sectional quantitative design was used to conduct the study. Data were collected through retrospective record review of 1200 maternity case records of the pregnant women who had attended for ANC services three or more times and was analysed using Statistical Package for Social Sciences (SPSS) version 21.0., Results: The majority of the processes detailed in the guidelines and principles of good care were evident in the records. However, several were missing or recorded in few reviews. These included the ANC plan, delivery plan, midwives' counter signatures on the cards, assessment for foetal congenital abnormalities, and consent for HIV testing., Conclusion: The study identified evidence of incomplete application of the BANC principles of good care and guidelines in pregnant women's antenatal care records which indicated that the BANC approach was not being successfully implemented. Recommendations were made with regards to policy development, institutional management and practise, nursing education, and further research to assist in successful implementation of the BANC approach in line with the guidelines and principles of good care.