NAFLD and nutraceuticals: a review of completed phase III and IV clinical trials

BackgroundNonalcoholic Fatty Liver Disease (NAFLD) has become a significant public health concern, affecting approximately one-fourth of the population. Despite its prevalence, no FDA-approved drug treatments specifically target NAFLD.AimTo provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database.MethodsThis review evaluates the current evidence by examining completed phase III and IV clinical trials registered on ClinicalTrials.gov. An exhaustive search was performed on April 17, 2023, using the terms “Nonalcoholic Fatty Liver Disease” and “NAFLD.” Two independent reviewers appraised eligible trials based on pre-defined inclusion and exclusion criteria.ResultsAn initial search yielded 1,226 clinical trials, with 12 meeting the inclusion criteria after filtration. The majority of trials focused on Omega-3 fatty acids (20.0%) and vitamin D (26.7%), followed by caffeine, chlorogenic acid, ginger, phosphatidylcholine, Trigonella Foenum-graecum seed extract, vitamin C, and vitamin E (each 6.7%). Most studies were Phase 3 (75.0%) and used a parallel assignment model (91.7%). Quadruple masking was the most prevalent technique (58.3%), and Iran was the leading country in terms of trial locations (25.0%). These interventions constitute two herbal interventions and nine supplement interventions.ConclusionThis reveals a diverse range of nutraceuticals, with Omega-3 fatty acids and vitamin D being predominant in the management of NAFLD. The global distribution of trials highlights the widespread interest in these therapeutics. However, more rigorous, large-scale trials are needed to establish safety, efficacy, and optimal dosages

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

In Vitro Assessment of Artificial Aging on the Antifungal Activity of PMMA Denture Base Material Modified with ZrO2 Nanoparticles

The antifungal effect of zirconium dioxide nanoparticles (ZrO2NPs) incorporated into denture base material has been inadequately investigated; additionally, to the authors’ knowledge, no studies have assessed the influence of artificial aging on the antifungal activity of these particles. Methodology. Heat-polymerized acrylic resin disks were fabricated and divided into four groups (0%, 1%, 2.5%, and 5% ZrO2NPs by weight). Antifungal activity was assessed using the direct culture and disk diffusion methods. Surface roughness and contact angles were measured using a profilometer and a goniometer, respectively. The artificial aging procedure was performed by repeating all tests at 7, 14, and 30 days following 2 rounds of thermocycling. Data were analyzed using ANOVA and Tukey’s post-hoc test (p<0.05). Results. The addition of ZrO2NPs significantly decreased the adhesion of Candida albicans with and without artificial aging procedures (p<0.001), while the disk diffusion methods did not reveal inhibition zones. ZrO2NP-modified specimens displayed significantly higher surface roughness compared to specimens in the control group (p<0.05) and showed the same behaviors with artificial aging procedures. The contact angle was significantly decreased in all modified groups in comparison to the control group (p<0.05). Conclusion. The addition of ZrO2NPs to polymethylmethacrylate denture base material reduced the adhesion of Candida albicans with a long-term antifungal effect. With the addition of ZrO2NPs, contact angles were decreased and surface roughness was increased; 1% was the most appropriate concentration. Clinical significance. The addition of ZrO2NPs to denture base material confers a long-term antifungal effect and could be used as a possible method for preventing and treating denture stomatitis

Effect of treated zirconium dioxide nanoparticles on the flexural properties of autopolymerized resin for interim fixed restorations: An in vitro study.

STATEMENT OF PROBLEM Fractures of interim fixed restorations are a common complication. The autopolymerized polymethyl methacrylate resin materials used for interim fixed restorations have limited mechanical properties, but whether adding treated zirconium dioxide nanoparticles improves mechanical properties is unclear. PURPOSE The purpose of this in vitro study was to evaluate the effect of treated zirconium dioxide nanoparticles on the flexural strength and elastic modulus of autopolymerized polymethyl methacrylate resin. MATERIAL AND METHODS A split-metal mold (60×10×3.3 mm) was used to fabricate 40 autopolymerized acrylic resin specimens. The specimens were divided into 4 groups (n=10) according to zirconium dioxide nanoparticle concentration: control (unmodified resin) and zirconium dioxide nanoparticle contents of 1, 2.5, and 5 wt%. The specimens were mixed and polymerized according to the manufacturer's instructions and stored in distilled water for 48 ±2 hours at 37 °C. The flexural strength and elastic modulus were evaluated based on the 3-point bend test where data were analyzed by using 1-way analysis of variance and Tukey post hoc tests (α=.05). RESULTS The flexural strength of the 1-wt% zirconium dioxide nanoparticle specimens was significantly higher than that of the control group (P.05). Elastic modulus significantly decreased with 2.5-wt% zirconium dioxide nanoparticles (P=.019), while no significant changes were found with other test groups (P>.05). CONCLUSIONS The addition of treated zirconium dioxide nanoparticles at low concentrations increased the flexural strength of autopolymerized polymethyl methacrylate resins used in fixed interim restorations

Water Sorption, Solubility, and Translucency of 3D-Printed Denture Base Resins

This study aimed to evaluate the water sorption, solubility, and translucency of 3D-printed denture base resins (NextDent, FormLabs, and Asiga), compare them to heat-polymerized acrylic denture base resins, and assess their performance under the effects of thermal cycling. A total of 80 acrylic disc specimens were used in the current study, categorized into four groups (n = 10); in one group, the samples were fabricated conventionally with a heat-polymerizing process (control), while the other three groups were fabricated digitally from different 3D-printed reins (NextDent, FormLabs, and Asiga). Specimens were fabricated according to the manufacturers&rsquo; recommendations and immersed in distilled water for 48 h at 37 &deg;C. Data on water sorption, solubility, and translucency measurements (T1) were obtained. All the specimens were subjected to 5000 thermal cycles, and then the measures were repeated using the same method (T2). Data analysis was attained via ANOVA and the post hoc Tukey test (&alpha; = 0.05). The type of resin significantly affected the values of water sorption, solubility, and translucency (p &lt; 0.001). The water sorption of 3D-printed resins was increased significantly in comparison to control with or without a thermal cycling effect. In terms of solubility, a significant increase in 3D-printed resins before thermocycling was observed; however, after thermocycling, Asiga had a significantly low value compared to the other groups (p &lt; 0.001). Thermal cycling increased the water sorption and solubility of all tested materials. In comparison to control, the translucency of the 3D-printed resins was significantly decreased (p &lt; 0.001). The translucency was significantly decreased per material in terms of the thermal cycling effect (before and after). NextDent showed significantly low translucency values (p &lt; 0.001) compared to the other groups. All 3D-printed resin groups had higher water sorption and solubility and lower translucency values in comparison to the heat-polymerized resin group. Regardless of resin types, thermal cycling adversely affected all tested properties

Influence of Different Conditioning Treatments on the Bond Integrity of Root Dentin to rGO Infiltrated Dentin Adhesive. SEM, EDX, FTIR and MicroRaman Study

The present study aimed to synthesize and equate the mechanical properties and dentin interaction of two adhesives; experimental adhesive (EA) and 5 wt.% reduced graphene oxide rGO) containing adhesive. Scanning electron microscopy (SEM)-Energy-dispersive X-ray spectroscopy (EDX), Micro-Raman spectroscopy, push-out bond strength test, and Fourier Transform Infrared (FTIR) spectroscopy were employed to study nano-bond strength, degree of conversion (DC), and adhesive-dentin interaction. The EA was prepared, and rGO particles were added to produce two adhesive groups, EA-rGO-0% (control) and rGO-5%. The canals of sixty roots were shaped and prepared, and fiber posts were cemented. The specimens were further alienated into groups based on the root canal disinfection technique, including 2.5% sodium hypochlorite (NaOCl), Photodynamic therapy (PDT), and ER-CR-YSGG laser (ECYL). The rGO nanoparticles were flake-shaped, and EDX confirmed the presence of carbon (C). Micro-Raman spectroscopy revealed distinct peaks for graphene. Push-out bond strength test demonstrated highest values for the EA-rGO-0% group after NaOCl and PDT conditioning whereas, rGO-5% showed higher values after ECYL conditioning. EA-rGO-0% presented greater DC than rGO-5% adhesive. The rGO-5% adhesive demonstrated comparable push-out bond strength and rheological properties to the controls. The rGO-5% demonstrated acceptable DC (although lower than control group), appropriate dentin interaction, and resin tag establishment

Influence of Different Conditioning Treatments on the Bond Integrity of Root Dentin to rGO Infiltrated Dentin Adhesive. SEM, EDX, FTIR and MicroRaman Study

The present study aimed to synthesize and equate the mechanical properties and dentin interaction of two adhesives; experimental adhesive (EA) and 5 wt.% reduced graphene oxide rGO) containing adhesive. Scanning electron microscopy (SEM)-Energy-dispersive X-ray spectroscopy (EDX), Micro-Raman spectroscopy, push-out bond strength test, and Fourier Transform Infrared (FTIR) spectroscopy were employed to study nano-bond strength, degree of conversion (DC), and adhesive-dentin interaction. The EA was prepared, and rGO particles were added to produce two adhesive groups, EA-rGO-0% (control) and rGO-5%. The canals of sixty roots were shaped and prepared, and fiber posts were cemented. The specimens were further alienated into groups based on the root canal disinfection technique, including 2.5% sodium hypochlorite (NaOCl), Photodynamic therapy (PDT), and ER-CR-YSGG laser (ECYL). The rGO nanoparticles were flake-shaped, and EDX confirmed the presence of carbon (C). Micro-Raman spectroscopy revealed distinct peaks for graphene. Push-out bond strength test demonstrated highest values for the EA-rGO-0% group after NaOCl and PDT conditioning whereas, rGO-5% showed higher values after ECYL conditioning. EA-rGO-0% presented greater DC than rGO-5% adhesive. The rGO-5% adhesive demonstrated comparable push-out bond strength and rheological properties to the controls. The rGO-5% demonstrated acceptable DC (although lower than control group), appropriate dentin interaction, and resin tag establishment