Kinetic modelling for polyphenol extraction from onion (Allium cepa) solid wastes using acidified water/ethanol mixture

Previous reports highlighted the onion solid wastes as abundant, residual material that might contain a significant load of antioxidant polyphenols. Although there have been studies pertaining to polyphenol recovery from onion wastes, the effect of temperature has not been adequately addressed. In this line, this study was undertaken with the aim of establishing a correlation between the extraction yield in total polyphenols and the extraction temperature, using acidified aqueous ethanol as the solvent system. Extraction of polyphenols from onion solid wastes was found to obey 2nd-order kinetics. On such a basis, the yield in total polyphenols at saturation could be very effectively determined and correlated with temperature using non-linear regression. The results indicated that the extraction yield at saturation is highly correlated with temperature, following a quadratic function. The extract obtained at optimal temperature (40 °C) had a total polyphenol yield of 21.10 mg gallic acid equivalents per gram of dry weight, and it was further analysed by liquid chromatography-mass spectroscopy to characterise its major constituents. The polyphenols detected were quercetin glucosides, as well as quercetin oxidation derivatives, including certain degradation products and dimers. The outcome of this study outlined that temperatures above 40 °C are rather not favourable for polyphenol extraction from onion solid wastes, as suggested by the model established through kinetics. The extract obtained under optimal conditions contained peculiar polyphenolic composition, not encountered in any other food processing residue

Factor VIII assay variability in postinfusion samples containing full length and B-domain deleted FVIII

Introduction Although the variability in factor VIII (FVIII):C measurement is well recognized, this has not been widely reported for post-FVIII infusion samples. Aim/Methods Three samples from haemophilia A patients were distributed in a UK National External Quality Assessment Scheme survey, each after treatment with either ReFacto AF, Kogenate FS or Advate. Fifty-two UK haemophilia centres performed FVIII assays using one-stage (n = 46) and chromogenic (n = 10) assays. Centres calibrated assays with the local plasma standard and with ReFacto AF laboratory standard for the ReFacto AF sample. Results/Conclusions Chromogenic assays gave significantly higher results than one-stage assays (P < 0.0001, 32% difference) in the post-Kogenate sample but not in the post-ReFacto AF (11% higher by chromogenic assay, ns) or post-Advate samples (3% lower by chromogenic, ns) when assays were calibrated with plasma standards. Twenty centres used all Instrumentation Laboratory (IL)-activated partial thromboplastin time reagents (Synthasil)/IL deficient plasma/reference plasma) in the one-stage assay and 15 used all Siemens reagents (Actin FS/Siemens deficient plasma/reference plasma); this made a significant difference to results post-ReFacto AF (41% higher by IL reagents, P < 0.0001) and Advate (39% higher by IL reagents, P < 0.0001), but not Kogenate (7% higher by IL, ns) when calibrated with plasma standards. Differences between results obtained with different one-stage assay reagents for monitoring Advate have implications for dosing patients. Furthermore, there was considerable inter-laboratory variation as indicated by CVs in the range 15–26% for chromogenic assay and 12–19% for one-stage assay results. This study suggests that external quality assessment schemes should offer participation in post-FVIII infusion schemes where haemophilic patients are monitored

Clotting and chromogenic factor VIII assay variability in post-infusion and spiked samples containing full-length recombinant FVIII or recombinant factor VIII Fc fusion protein (rFVIIIFc).

INTRODUCTION: Variability in FVIII measurement is a recognized problem. There are limited data for samples containing recombinant Factor VIII Fc fusion protein (rFVIIIFc). Many studies use samples for which factor concentrate has been spiked into FVIII deficient plasma in vitro. This approach requires validation. AIM/METHODS: Four samples were distributed in a UK National External Quality Assessment Scheme for Blood Coagulation (NEQAS BC) survey. One contained Advate (full-length recombinant FVIII) (rFVIII) added to FVIII deficient plasma, one was from a severe haemophilia A patient after infusion of Advate, one was prepared by addition of rFVIIIFc (marketed as Elocta/Eloctate) to FVIII deficient plasma and the fourth was collected from a severe haemophilia A patient following rFVIIIFc (Eloctate) infusion. Fifty-three haemophilia centres (UK and Scandinavia) performed one-stage FVIII assays and 27 performed chromogenic FVIII assays. RESULTS/CONCLUSIONS: One-stage assays gave significantly lower results than chromogenic assays by 7% (P < 0.01) and 13%(P < 0.001) for post-Advate and Advate spiked samples, and by 22% (P < 0.001) and 23% (P < 0.001) for post-rFVIIIFc and rFVIIIFc spiked samples. The interlaboratory variation was similar for all samples, with CVs of 12%-16% (chromogenic) and 10%-13% (one stage). The data indicate that either product can be safely monitored by one-stage or chromogenic assay. Spiked samples behaved in a similar way to post-infusion samples for both products and could be substituted for post-infusion samples for use in proficiency testing exercises (ie, samples were commutable)

Delivery of AAV‐based gene therapy through haemophilia centres—A need for re‐evaluation of infrastructure and comprehensive care: A Joint publication of EAHAD and EHC

Introduction Adeno-associated virus (AAV)-based gene therapy for haemophilia presents a challenge to the existing structure of haemophilia centres and requires a rethink of current collaboration and information exchange with the aim of ensuring a system that is fit-for-purpose for advanced therapies to maximise benefits and minimise risks. In Europe, a certification process based on the number of patients and facilities is offered to the haemophilia centres by European Haemophilia Network (EUHANET). Aim and methods This joint European Association for Haemophilia and Allied Disorders (EAHAD) and European Haemophilia Consortium (EHC) publication describes criteria for centres participating in gene therapy care that require a reassessment of the infrastructure of comprehensive care and provides an outlook on how these criteria can be implemented in the future work of haemophilia centres. Results The core definition of a haemophilia treatment centre remains, but additional roles could be implemented. A modifiable ‘hub-and-spoke’ model addresses all aspects associated with gene therapy, including preparation and administration of the gene therapy product, determination of coagulation and immunological parameters, joint score and function, and liver health. This will also include the strategy on how to follow-up patients for a long-term safety and efficacy surveillance. Conclusion We propose a modifiable, networked ‘hub and spoke’ model with a long term safety and efficacy surveillance system. This approach will be progressively developed with the goal of making haemophilia centres better qualified to deliver gene therapy and to make gene therapy accessible to all persons with haemophilia, irrespective of their country or centre of origin

Composição fenólica e atividade antioxidante de resíduos agroindustriais

Atualmente, são produzidas milhões de toneladas de resíduos provenientes do processamento agroindustrial. Muitos deles são ricos em compostos bioativos sendo potenciais fontes naturais dessas substâncias. Assim, este trabalho teve como objetivo avaliar o teor de compostos fenólicos totais, a atividade antioxidante e a composição fenólica de três resíduos gerados por agroindústrias brasileiras: bagaço de uva Isabel (BI) (Vitis labrusca), bagaço de uva Verdejo (BV) (Vitis vinifera) e bagaço de goiaba (BG) (Psidium guajava). Os resultados do teor de compostos fenólicos totais (mg GAE g-1) encontrados nos extratos etanólicos e aquosos dos resíduos foram, respectivamente: BV (20,94±0,46; 8,03±0,43)> BI (16,57±0,19; 4,41±0,01)> BG (3,41±0,09; 1,88±0,06). Alta atividade antioxidante, principalmente em BV e BI, foi verificada nos ensaios realizados (ABTS , DPPH e autooxidação do sistema beta-caroteno/ácido linoléico). Uma forte correlação positiva entre atividade antioxidante e o teor de compostos fenólicos totais foi encontrada. Os compostos fenólicos encontrados, por cromatografia gasosa com espectrometria de massas (CG-EM), foram: ácido gálico, epicatequina, quercetina (BV, BI e BG); ácido isovanílico (BI, BG); ácido p-cumárico (BI); ácido caféico e resveratrol (BV, BI). Esses resultados mostram que os resíduos agroindustriais analisados, particularmente os vinícolas, são ricos em substâncias bioativas e podem ser explorados pela indústria de alimentos e farmacêutica

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

Polyphenolic antioxidants from agri-food waste biomass

[No abstract available

Glycerol and glycerol-based deep eutectic mixtures as emerging green solvents for polyphenol extraction: The evidence so far

The acknowledgement that uncontrolled and excessive use of fossil resources has become a prime concern with regard to environmental deterioration, has shifted the orientation of economies towards the implementation of sustainable routes of production, through the valorization of biomass. Green chemistry plays a key role in this regard, defining the framework of processes that encompass eco-friendly methodologies, which aim at the development of highly efficient production of numerous bioderived chemicals, with minimum environmental aggravation. One of the major concerns of the chemical industry in establishing sustainable routes of production, is the replacement of fossil-derived, volatile solvents, with bio-based benign ones, with low vapor pressure, recyclability, low or no toxicity, availability and low cost. Glycerol is a natural substance, inexpensive and non-toxic, and it is a principal by-product of biodiesel industry resulting from the transesterification process. The ever-growing market of biodiesel has created a significant surplus of glycerol production, resulting in a concomitant drop of its price. Thus, glycerol has become a highly available, low-cost liquid, and over the past decade its use as an alternative solvent has been gaining unprecedented attention. This review summarizes the utilization of glycerol and glycerol-based deep eutectic mixtures as emerging solvents with outstanding prospect in bioactive polyphenol extraction. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Hydroxypropyl-β-cyclodextrin as a green co-solvent in the aqueous extraction of polyphenols from waste orange peels

There is, to-date, an expanding interest concerning the use of cyclodextrins as green food-grade co-solvents in the aqueous extraction of polyphenols, however, data regarding polyphenol extraction from waste orange peels (WOP) are lacking. On this ground, hydroxypropyl β-cyclodextrin (HP-β-CD), a highly water-soluble cyclodextrin, was used to develop a simple and straightforward methodology for the effective recovery of WOP polyphenols. Process optimization by response surface showed that maximum total polyphenol recovery (26.30 ± 1.49 mg gallic acid equivalents g−1 dry mass) could be accomplished with 15 mM HP-β-CD at 40◦C. On the other hand, integration of ultrasonication pretreatment was found unsuitable, as it resulted in reduced polyphenol yield. Examination of solvent acidity indicated that polyphenol extraction may be enhanced at pH 4, but the difference was non-significant (p &gt; 0.05) compared to yields attained at pH 2, 3, and 5. Extraction of WOP polyphenols with HP-β-CD was shown to provide significantly higher hesperidin yield compared to 60% (v/v) aqueous ethanol, which suggested selectivity of HP-β-CD toward this polyphenolic metabolite. © 2020 by the authors. Licensee MDPI, Basel, Switzerland