High-sensitivity C-reactive protein among people living with HIV on highly active antiretroviral therapy: a systemic review and meta-analysis.

The pathological consequences of inflammation persist in people living with the human immunodeficiency virus (PLWH), regardless of the positive outcomes of highly active antiretroviral therapy (HAART). The current systematic review and meta-analysis aims to understand and explore the levels of high-sensitivity C-reactive protein (hs-CRP) and other cardiovascular disease (CVD)-risk factors including lipid profiles among PLWH on HAART. Major electronic databases including PubMed, Scopus, and Web of Science were searched to retrieve relevant global literature reporting on hs-CRP levels in PLWH on HAART. A total of twenty-two studies with an average participant age of 40 years were eligible for this systematic review and meta-analysis. Majority of the included studies were from Africa (n = 11), the United States (n = 6), and Europe (n = 5). Our systemic review showed that most studies reported increased levels of hs-CRP among PLWH on HAART when compared to controls (PLWH not on HAART or those without HIV), especially in studies from Africa. This was supported by a meta-analysis showing significantly elevated levels of hs-CRP in PLWH on HAART when compared to PLWH not on HAART (standardised mean difference [SMD] = 0.56; 95% CI = 0.10­1.01, z = 2.41; p = 0.02) or those without HIV (SMD = 1.19; 95% CI = 0.76­1.63, z = 5.35; p < 0.001). Where lipid profiles, as a major predictor for CVD risk, were also impaired in PLWH on HAART when compared to PLWH not on HAART and HIV-negative participants. In conclusion, elevated levels of hs-CRP and lipid levels are prevalent in PLWH on HAART, this may increase the risk of CVD complications, especially for those people living in Africa. However, more evidence in larger population studies is required to confirm these outcomes and unveil any possible clinical implications of HAART-induced modulation of hs-CRP levels in PLWH.

A systematic review assessing the association of inflammatory markers with kidney dysfunction in people living with HIV on highly active antiretroviral therapy.

Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.

High-dose oral contraceptives induce hyperinsulinemia without altering immune activation in diet-induced obesity which persists even following a dietary low-fat diet intervention.

Combined oral contraceptives (COCs) are known to cause weight gain and alter metabolic and immunological pathways. However, modifications in arterial or venous thrombotic risk profiles of women of reproductive ages on COC remain unclear. The study aimed at assessing the impact of COC on immune activation in diet-induced obesity. We further established whether the dietary intervention of switching from a high-fat diet (HFD) to a low-fat diet (LFD) attenuates immunological responses. Twenty (n=20) five-week-old female Sprague Dawley rats were randomly divided into two diet groups of HFD (n=15) and LFD (n=5) and were monitored for eight weeks. After eight weeks, animals in the HFD group switched diets to LFD and were randomly assigned to receive high-dose COC (HCOC) or low-dose COC (LCOC) for six weeks. Animals on HFD significantly gained weight and had a higher lee index when compared to the LFD group (p < 0.05). Moreover, the triglyceride-glucose index, insulin, and other metabolic parameters also increased in the HFD group compared to the LFD group (p < 0.001). Consistently, the levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), were elevated in the HFD group when compared to the LFD group (p < 0.05). Upon switching from a high-fat to a low-fat diet, insulin levels persistently increased in animals receiving HCOC treatment compared to the LFD and HFD/LFD groups (p < 0.05). Thus, in a rat model of HFD-feeding, short-term HCOC treatment induces long-term metabolic dysregulation, which persists despite dietary intervention. However, further studies are recommended to confirm these findings.

Effect of combined oral contraceptive on cardiorespiratory function and immune activation in premenopausal women involved in exercise: A systematic review protocol.

BACKGROUND: The use of combined oral contraceptive (COC) is common among women of reproductive age despite the potential risk of them developing thrombotic events. There is a need to understand how COC affects cardiorespiratory function and markers of immune activation in premenopausal women involved in exercise. This highlights a need for a systematic review to enhance our understanding of how the use of COC affects cardiovascular health in premenopausal women subjected to exercise. METHOD: This systematic review protocol was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 statement. An extensive search of relevant literature by two independent reviewers will be conducted through the EBSCOhost interface to access databases such as MEDLINE, EMBASE, and CINAHL. Other health sources, including Cochrane CENTRAL, unpublished studies and grey literature, will also be searched. The search will include all studies that report the effect of COC on essential parameters of cardiorespiratory function and markers of immune activation in premenopausal women involved in exercise. All included studies will be appraised using appraisal tools, while appropriate extraction tools will be used for data extraction. Where possible, eligible studies will be pooled for meta-analysis. If statistical pooling is not feasible, our findings will be presented in a narrative format. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation Assessment (GRADE) tool. TRIAL REGISTRATION: PROSPERO registration number: CRD42021265257.

Low circulating levels of neuregulin 4 as a potential biomarker associated with the severity and prognosis of obesity-related metabolic diseases: a systematic review.

BACKGROUND: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases. AIM: To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). METHODS: A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines. RESULTS: Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD. CONCLUSION: Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.

Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies.

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.

Brown adipose tissue-derived metabolites and their role in regulating metabolism.

The discovery and rejuvenation of metabolically active brown adipose tissue (BAT) in adult humans have offered a new approach to treat obesity and metabolic diseases. Beyond its accomplished role in adaptive thermogenesis, BAT secretes signaling molecules known as "batokines", which are instrumental in regulating whole-body metabolism via autocrine, paracrine, and endocrine action. In addition to the intrinsic BAT metabolite-oxidizing activity, the endocrine functions of these molecules may help to explain the association between BAT activity and a healthy systemic metabolic profile. Herein, we review the evidence that underscores the significance of BAT-derived metabolites, especially highlighting their role in controlling physiological and metabolic processes involving thermogenesis, substrate metabolism, and other essential biological processes. The conversation extends to their capacity to enhance energy expenditure and mitigate features of obesity and its related metabolic complications. Thus, metabolites derived from BAT may provide new avenues for the discovery of metabolic health-promoting drugs with far-reaching impacts. This review aims to dissect the complexities of the secretory role of BAT in modulating local and systemic metabolism in metabolic health and disease.

A systematic review assessing the potential use of cystatin c as a biomarker for kidney disease in people living with HIV on antiretroviral therapy.

The introduction of antiretroviral therapy (ART) has significantly prolonged the lifespan of people living with human immunodeficiency virus (PLWH). However, the sustained use of this drug regimen has also been associated with a cluster of metabolic anomalies, including renal toxicity, which can lead to the development of kidney diseases. In this study, we reviewed studies examining kidney disease in PLWH sourced from electronic databases such as PubMed/MEDLINE, Scopus, and Google Scholar, as well as gray literature. The narrative synthesis of data from these clinical studies demonstrated that the serum levels of cystatin C remained unchanged or were not affected in PLWH on ART, while the creatinine-based glomerular filtration rate (GFR) fluctuated. In fact, some of the included studies showed that the creatinine-based GFR was increased in PLWH taking tenofovir disoproxil fumarate-containing ART, perhaps indicating that the use of both cystatin C- and creatinine-based GFRs is vital to monitor the development of kidney disease in PLWH. Clinical data summarized within this study indicate the potential detrimental effects of tenofovir-based ART regimens in causing renal tubular injury, while highlighting the possible beneficial effects of dolutegravir-based ART on improving the kidney function in PLWH. However, the summarized literature remains limited, while further clinical studies are required to provide insights into the potential use of cystatin C as a biomarker for kidney disease in PLWH.

Low levels and partial exposure to palmitic acid improves mitochondrial function and the oxidative status of cultured cardiomyoblasts.

Lipid overload or metabolic stress has gained popularity in research that explores pathological mechanisms that may drive enhanced oxidative myocardial damage. Here, H9c2 cardiomyoblasts were exposed to various doses of palmitic acid (0.06 to 1 mM) for either 4 or 24 h to study its potential physiological response to cardiac cells. Briefly, assays performed included metabolic activity, cholesterol content, mitochondrial respiration, and prominent markers of oxidative stress, as well as determining changes in mitochondrial potential, mitochondrial production of reactive oxygen species, and intracellular antioxidant levels like glutathione, glutathione peroxidase and superoxide dismutase. Cellular damage was probed using fluorescent stains, annexin V and propidium iodide. Our results indicated that prolonged exposure (24-hours) to palmitic acid doses ≥ 0.5 mM significantly impaired mitochondrial oxidative status, leading to enhanced mitochondrial membrane potential and increased mitochondrial ROS production. While palmitic acid dose of 1 mM appeared to induce prominent cardiomyoblasts damage, likely because of its capacity to increase cholesterol content/ lipid peroxidation and severely suppressing intracellular antioxidants. Interestingly, short-term (4-hours) exposure to palmitic acid, especially for lower doses (≤ 0.25 mM), could improve metabolic activity, mitochondrial function and protect against oxidative stress induced myocardial damage. Potentially suggesting that, depending on the dose consumed or duration of exposure, consumption of saturated fatty acids such as palmitic acid can differently affect the myocardium. However, these results are still preliminary, and in vivo research is required to understand the significance of maintaining intracellular antioxidants to protect against oxidative stress induced by lipid overload.

Global trends in clinical trials and interventions for the metabolic syndrome: A comprehensive analysis of the WHO International Clinical Trials platform.

Metabolic syndrome has emerged as a significant global public health concern, necessitating comprehensive examination alongside cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D). This study provides a comprehensive analysis of clinical trials, drawing upon data sourced from the International Clinical Trials Registry Platform (ICTRP), until April 2023. Information pertaining to trial attributes and intervention features was gathered and subsequently summarized. Among the 2379 studies found on ICTRP from 18 clinical registries, ClinicalTrials.gov was the most popular with 55 % of the studies, based on data emerging from the United States. Most trials were for treatment (44 %) and prevention (17 %), with fewer focused on basic science, and diagnostic purposes. Diet and exercise were the most prominent, with 710 and 247 studies, respectively. Metformin and statins emerge as leading pharmacological therapies, reflecting the prevalence of CVD and T2D in the context of metabolic syndrome. However, there is growing recognition of other promising interventions, such as Glucagon-Like Peptide-1 agonists and Dipeptidyl Peptidase IV inhibitors, which offer potential in slowing the progression of metabolic syndrome-related conditions. Notably, clinical trials primarily assessed diagnostic markers like lipid profiles, insulin, and blood pressure, rather than body mass and body mass index. These parameters are crucial for evaluating the effectiveness and safety of interventions for metabolic syndrome due to its multi-condition nature. Most studies aimed to address general symptom relief, while highlighting a need for additional well-designed treatment trials with rigorous methodologies in accordance with the World Health Organization's guidance for consistent evaluation and treatment.

Prevalence of chronic kidney disease and associated risk factors among people living with HIV in a rural population of Limpopo Province, South Africa.

Background: Limited evidence informs on the prevalence of chronic kidney disease (CKD) in people living with HIV (PLWH) in South Africa. Thus, this study aimed to determine the prevalence of CKD and its associated risk factors among PLWH within the rural province of Limpopo, South Africa. Methods: We conducted a cross-sectional study of 143 participants, subdivided into groups of PLWH (n = 103) and individuals without HIV (n = 43). Structured questionnaires were used to collect and capture sociodemographic information including age, sex, alcohol intake, smoking status, and educational status. Basic measurements taken included levels of cluster of differentiation 4 (CD4+) count, body mass index (BMI), blood pressure, plasma cystatin C, and fasting serum glucose levels. Plasma cystatin C-based estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD-EPI) estimator to determine the prevalence of CKD. Results: The prevalence of CKD was approximately 7% in PLWH. Multivariate logistic regression analysis showed that it was only diabetes mellitus (odds ratio of 5.795, 95% confidence interval, p = 0.034) and age (odds ratio of 1.078, 95% confidence interval, p = 0.039) that were significantly associated with CKD in PLWH. Conclusion: Chronic kidney disease was prevalent in PLWH, and it was further associated with cardiovascular risk factors, diabetes, and ageing. As PLWH age, the burden of CKD may be increased with the increase in cardiovascular-related comorbidities such as diabetes.

Trends in Vaccine Completeness in Children Aged 0-23 Months in Cape Town, South Africa.

BACKGROUND: We have previously determined that the occurrence of missed vaccination opportunities in children in Cape Town, South Africa, is shaped by both individual and contextual factors. These factors present valuable openings for enhancing quality and implementing broader strategies to enhance the delivery of routine Immunisation services. METHODS: Here, we are further reporting regional-level data on the coverage and factors influencing vaccination completion within a similar study population, based on extensive data analysis from the 2016 South African Demographic and Health Survey. RESULTS AND DISCUSSION: The study reveals commendable vaccination coverage for most vaccines within recommended schedules, with high rates of initial vaccinations at birth and during the primary vaccination schedule. However, there are notable areas for improvement, particularly in ensuring complete coverage for the second measles vaccine and the 18-month vaccine. Socio-demographic factors also play a role, with maternal education and caregiver awareness campaigns showing the potential to positively influence vaccination completeness. This study emphasises the importance of timely vaccinations during the early months of life and underscores the need for interventions to maintain coverage as children age. Specific sub-districts, such as Tygerberg, may require targeted efforts to enhance vaccination completeness. Additionally, assessing caregiver knowledge about child vaccination is deemed vital, as it can impact vaccination decisions and adherence. CONCLUSIONS: The findings provide valuable insights for public health interventions in Cape Town, aimed at reducing the burden of vaccine-preventable diseases and ensuring the health of the region's youngest population.