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.

Exploring the complexity of the implementation determinants of human papillomavirus vaccination in Africa through a systems thinking lens: A rapid review.

A rapid review was conducted to explore the implementation determinants of human papillomavirus (HPV) vaccination in the World Health Organization African Region and describe their dynamic relationship. PubMed and Google Scholar were searched in October 2023 to find relevant literature. A total of 64 published studies that reported factors affecting HPV vaccination were identified. Analysis of identified factors yielded 74 implementation determinants of HPV vaccination across the five domains of the Consolidated Framework for Implementation Research (CFIR): two (2.70%) were in the innovation domain, seven (9.46%) were in the outer setting domain, 14 (18.92%) were in the inner setting domain, 37 (50%) were in the individual domain and 14 (18.92%) were in the implementation process domain. A causal loop diagram of these implementation determinants revealed four balancing and seven reinforcing loops. Applying systems lens promoted a more holistic understanding of the implementation determinants of HPV vaccination, exposing leverage points for interventions.

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.

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.

Socio-Demographic Factors Influencing Malaria Vaccine Acceptance for Under-Five Children in a Malaria-Endemic Region: A Community-Based Study in the Democratic Republic of Congo.

Two novel vaccines against malaria are proposed as a complementary control tool to prevent and reduce Plasmodium falciparum related disease and death in under-five children from moderate to high malaria transmission regions. The Democratic Republic of Congo (DRC) has committed to eradicate malaria by 2030, and significant efforts have been deployed to strengthen control and elimination measures. We aimed to understand factors influencing the malaria vaccine acceptability among the general population in eastern DRC. We conducted a survey among adult Congolese in Bukavu in March 2022. The questionnaire was adapted from the Behavioral and Social Drivers of vaccine uptake (BeSD) framework and was administered online and physically. Multivariate logistic regressions were built, and estimates were represented as adjusted odds ratios (aOR) and corresponding 95% confidence intervals (95%CI). Out of 1612 adults (median age: 39 years, 46.15% female) surveyed, only 7.26% were aware of the malaria vaccine. However, 46.53% expressed willingness to vaccinate themselves, and 52.60% were open to vaccinating their under-five children. Adjusting for confounding factors, non-student/non-healthcare worker professions (aOR = 0.58, 95%CI [0.42-0.78]) and middle-income status (aOR = 1.87, 95%CI [1.25-2.80]) were significantly associated with self-vaccination acceptance. Age played a role in under-five child vaccination acceptability, with 25 to over 64 years showing increased acceptability compared to the 18-24 age group. Additionally, non-student/non-healthcare worker professions (aOR = 1.88, 95%CI [1.37-2.59]), medium education levels (aOR = 2.64, 95%CI [1.29-5.79]), and residing in semi-rural areas (aOR = 1.63, 95%CI [1.27-2.10]) were predictors of under-five child vaccination acceptance. The acceptability of the malaria vaccine for self and for under-five children was suboptimal for effective malaria control in this community in the DRC. Our study constitutes a call for the Expanded Program on Immunization to closely work with various stakeholders to strengthen risk communication for community engagement prior to and during the introduction of this novel and lifesaving tool, malaria vaccination.

COVID-19 Vaccine Hesitancy and Associated Oral Cholera Vaccine Hesitancy in a Cholera-Endemic Country: A Community-Based Cross-Sectional Study in the Democratic Republic of Congo.

COVID-19 vaccine hesitancy and its enablers shape community uptake of non-covid vaccines such as the oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera-endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included demographics, intention to take OCV and COVID-19 vaccines, reasons for COVID-19 hesitancy, and thoughts and feelings about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude prevalence ratio, [cPR] = 1.12, 95%CI [1.03-1.21]). Independent predictors of OCV hesitancy were living in a semi-urban area (adjusted prevalence ratio [aPR] = 1.10, 95%CI [1.03-1.12]), religious refusal of vaccines (aPR = 1.06, 95%CI [1.02-1.12]), concerns about vaccine safety (aPR = 1.05, 95%CI [1.01-1.11]) and adverse effects (aPR = 1.06, 95%CI [1.01-1.12]), as well as poor vaccine literacy (aPR = 1.07, 95%CI [1.01-1.14]). Interestingly, the belief in COVID-19 vaccine effectiveness reduced OCV hesitancy by 24% (aPR = 0.76, 95%CI [0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibited a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy and trust-building interventions would likely improve the introduction of novel non-COVID-19 vaccines in the post-COVID-19 era.

Informal health sector and routine immunization: making the case for harnessing the potentials of patent medicine vendors for the big catch-up to reduce zero-dose children in sub-Saharan Africa.

The COVID-19 pandemic caused a surge in the number of unimmunized and under-immunized children in Africa. The majority of unimmunized (or zero-dose) children live in hard-to-reach rural areas, urban slums, and communities affected by conflict where health facilities are usually unavailable or difficult to access. In these settings, people mostly rely on the informal health sector for essential health services. Therefore, to reduce zero-dose children, it is critical to expand immunization services beyond health facilities to the informal health sector to meet the immunization needs of children in underserved places. In this perspective article, we propose a framework for the expansion of immunization services through the informal health sector as one of the pillars for the big catch-up plan to improve coverage and equity. In African countries like Nigeria, Ethiopia, Tanzania, and the Democratic Republic of Congo, patent medicine vendors serve as an important informal health sector provider group, and thus, they can be engaged to provide immunization services. A hub-and-spoke model can be used to integrate patent medicine vendors into the immunization system. A hub-and-spoke model is a framework for organization design where services that are provided by a central facility (hub) are complimented by secondary sites (spokes) to optimize access to care. Systems thinking approach should guide the design, implementation, and evaluation of this model.

Positioning implementation science in national immunization programmes to improve coverage equity and advance progress toward Immunization Agenda 2030: An urgent global health imperative.

Despite the availability of effective vaccines for preventing common childhood infectious diseases, there is still significant disparities in access and utilization across many low- and middle-income countries (LMIC). The factors that drive these disparities are often multilevel, originating from individuals, health facilities, health systems and communities, and also multifaceted. Implementation science has emerged as a field to help address "know-do" gaps in health systems, and can play a significant role in strengthening immunization systems to understand and solve implementation barriers that limit access and uptake within their contexts. This article presents a reflexive perspective on how to position implementation research in immunization programmes to improve coverage equity. Furthermore, key points of synergy between implementation research and vaccination are highlighted, and some potential practice changes that can be applied within specific contexts were proposed. Using a human rights lens, it was concluded that the cost that is associated with implementation failure in immunization programmes is significant and unjust, and future directions for implementation research to optimize its application in practice settings have been recommended.

Assessing the Implementation Determinants of Pilot Malaria Vaccination Programs in Ghana, Kenya, and Malawi through a Complexity Lens: A Rapid Review Using a Consolidated Framework for Implementation Research.

In 2019, national immunization programs in Ghana, Kenya, and Malawi commenced the implementation of RTS,S/AS01 vaccination in large-scale pilot schemes. Understanding the implementation context of this malaria vaccination in the pilot countries can provide useful insights for enhancing implementation outcomes in new countries. There has not yet been a proper synthesis of the implementation determinants of malaria vaccination programs. A rapid review was conducted to identify the implementation determinants of the pilot malaria vaccination programs in Ghana, Kenya, and Malawi, and describe the mechanism by which these determinants interact with each other. A literature search was conducted in November 2023 in PubMed and Google Scholar to identify those studies that described the factors affecting malaria vaccine implementation in Ghana, Kenya, and Malawi. Thirteen studies conducted between 2021 and 2023 were included. A total of 62 implementation determinants of malaria vaccination across all five domains of the consolidated framework for implementation research (CFIR) were identified. A causal loop diagram showed that these factors are interconnected and interrelated, identifying nine reinforcing loops and two balancing loops. As additional countries in Africa prepare for a malaria vaccine roll-out, it is pertinent to ensure that they have access to adequate information about the implementation context of countries that are already implementing malaria vaccination programs so that they understand the potential barriers and facilitators. This information can be used to inform context-specific systems enhancement to maximize implementation success. Going forward, primary implementation studies that incorporate the causal loop diagram should be integrated into the malaria vaccine implementation program to enable immunization program managers and other key stakeholders to identify and respond to emerging implementation barriers in a timely and systematic manner, to improve overall implementation performance.

Sustainable financing for vaccination towards advancing universal health coverage in the WHO African region: The strategic role of national health insurance.

There is a growing political interest in health reforms in Africa, and many countries are choosing national health insurance as their main financing mechanism for universal health coverage. Although vaccination is an essential health service that can influence progress toward universal health coverage, it is not often prioritized by these national health insurance systems. This paper highlights the potential gains of integrating vaccination into the package of health services that is provided through national health insurance and recommends practical policy actions that can enable countries to harness these benefits at population level.

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.

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.

The impact of DNA methylation as a factor of Adverse Pregnancy and Birth Outcomes (APBOs): a systematic review protocol.

BACKGROUND: Deoxyribonucleic acid (DNA) methylation is one of the epigenetic modifications that has gained a lot of interest as a factor influencing fetal programming and as a biomarker for adverse pregnancy and birth outcomes (APBOs). Epidemiological studies have demonstrated that DNA methylation can result in adverse pregnancy and birth outcomes (APBOs) including miscarriage, intrauterine growth restriction (IUGR), low birth weight (LBW), sepsis, and preterm birth (PTB), which may later result in diseases in adulthood. However, the mechanism by which DNA methylation influences these APBOs remains unclear. The systematic review will assess the association between global and gene-specific DNA methylation with adverse pregnancy outcomes. METHOD: The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 checklist will be followed when conducting this systematic review. To develop the search strategy the PI(E)COS (population, intervention/exposure, comparator/control, outcome, and study designs) framework will be followed. Thus far, the research team has retrieved 4721 from Cochrane Library, PubMed, Web of Sciences, and MEDLINE. Out of these, 584 studies have been screened for eligibility, and approximately 124 studies meet the inclusion criteria. Pending the search results identified from the grey literature. For identification of unpublished studies in journals indexed in electronic databases, Google Scholar will be used. I.M and A.S will separately extract data from the articles and screen them, if there are any disagreements between I.M and A.S, then the L.M will resolve them. The methodological quality and bias risk of the included studies will be evaluated using the Critical Appraisal Skill Programme CASP) checklist. [Formula: see text] and [Formula: see text] alpha = 0.10 statistic will be used for assessing statistical heterogeneity between studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess and grade the overall quality of extracted data. ETHICS AND DISSEMINATION: Ethical approval is not required. The systematic review will assess available literature on possible associations between DNA methylation with adverse pregnancy and birth outcomes (APBOs) including LBW, IUGR, miscarriage, sepsis, and PTB. The findings could help guide future research assessing DNA methylation and other APBOs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRCRD42022370647.

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.

Potential Benefits of Coffee Consumption on Improving Biomarkers of Oxidative Stress and Inflammation in Healthy Individuals and Those at Increased Risk of Cardiovascular Disease.

Cardiovascular diseases (CVDs) are considered the predominant cause of death globally. An abnormal increase in biomarkers of oxidative stress and inflammation are consistently linked with the development and even progression of metabolic diseases, including enhanced CVD risk. Coffee is considered one of the most consumed beverages in the world, while reviewed evidence regarding its capacity to modulate biomarkers of oxidative stress and inflammation remains limited. The current study made use of prominent electronic databases, including PubMed, Google Scholar, and Scopus to retrieve information from randomized controlled trials reporting on any association between coffee consumption and modulation of biomarkers of oxidative stress and inflammation in healthy individuals or those at increased risk of developing CVD. In fact, summarized evidence indicates that coffee consumption, mainly due to its abundant antioxidant properties, can reduce biomarkers of oxidative stress and inflammation, which can be essential in alleviating the CVD risk in healthy individuals. However, more evidence suggests that regular/prolonged use or long term (>4 weeks) consumption of coffee appeared to be more beneficial in comparison with short-term intake (<4 weeks). These positive effects are also observed in individuals already presenting with increased CVD risk, although such evidence is very limited. The current analysis of data highlights the importance of understanding how coffee consumption can be beneficial in strengthening intracellular antioxidants to alleviate pathological features of oxidative stress and inflammation to reduce CVD risk within the general population. Also covered within the review is essential information on the metabolism and bioavailability profile of coffee, especially caffeine as one of its major bioactive compounds.

Bioactive Properties, Bioavailability Profiles, and Clinical Evidence of the Potential Benefits of Black Pepper (Piper nigrum) and Red Pepper (Capsicum annum) against Diverse Metabolic Complications.

The consumption of food-derived products, including the regular intake of pepper, is increasingly evaluated for its potential benefits in protecting against diverse metabolic complications. The current study made use of prominent electronic databases including PubMed, Google Scholar, and Scopus to retrieve clinical evidence linking the intake of black and red pepper with the amelioration of metabolic complications. The findings summarize evidence supporting the beneficial effects of black pepper (Piper nigrum L.), including its active ingredient, piperine, in improving blood lipid profiles, including reducing circulating levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in overweight and obese individuals. The intake of piperine was also linked with enhanced antioxidant and anti-inflammatory properties by increasing serum levels of superoxide dismutase while reducing those of malonaldehyde and C-reactive protein in individuals with metabolic syndrome. Evidence summarized in the current review also indicates that red pepper (Capsicum annum), together with its active ingredient, capsaicin, could promote energy expenditure, including limiting energy intake, which is likely to contribute to reduced fat mass in overweight and obese individuals. Emerging clinical evidence also indicates that pepper may be beneficial in alleviating complications linked with other chronic conditions, including osteoarthritis, oropharyngeal dysphagia, digestion, hemodialysis, and neuromuscular fatigue. Notably, the beneficial effects of pepper or its active ingredients appear to be more pronounced when used in combination with other bioactive compounds. The current review also covers essential information on the metabolism and bioavailability profiles of both pepper species and their main active ingredients, which are all necessary to understand their potential beneficial effects against metabolic diseases.