The increasing interest in Aronia melanocarpa berries for their antioxidant properties sets the necessity to define sustainable strategies to valorize the by-products. This study investigates the use of supercritical carbon dioxide (scCO2) extraction, with and without ethanol as a co-solvent, for recovering lipophilic and phenolic compounds from aronia pomace. Extractions were performed at 20, 30, and 40 MPa and temperatures of 50, 70, and 90 °C. A yield of about 2.7 g per 100 g of dried pomace was obtained at 40 MPa and 90 °C. However, the highest total phenolic content of about 165 mg of gallic acid equivalent per 100 g of dried pomace was achieved with 5 % ethanol co-solvent at 50 °C and 30 MPa. The lipid extracts were rich in linoleic acid and the wax portion increased under low-density scCO2 conditions. A feedforward neural network was developed to model extraction kinetics and predict yield as a function of temperature, pressure, and time, demonstrating high predictive accuracy. These findings highlight scCO2 extraction as a viable route for the efficient and selective recovery of valuable bioactives from aronia pomace, contributing to a circular bioeconomy.
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Background: Currently, the Ponseti method is the gold standard for treatment of clubfeet. For long-term func- tional evaluation of this method, gait analysis can be performed. Previous studies have assessed gait differences between Ponseti treated clubfeet and healthy controls. Research question/purpose: The aims of this systematic review were to compare the gait kinetics of Ponseti treated clubfeet with healthy controls and to compare the gait kinetics between clubfoot patients treated with the Ponseti method or surgically. Methods: A systematic search was performed in Embase, Medline Ovid, Web of Science, Scopus, Cochrane, Cinahl ebsco, and Google scholar, for studies reporting on gait kinetics in children with clubfeet treated with the Ponseti method. Studies were excluded if they only used EMG or pedobarography. Data were extracted and a risk of bias was assessed. Meta-analyses and qualitative analyses were performed. Results: Nine studies were included, of which five were included in the meta-analyses. The meta-analyses showed that ankle plantarflexor moment (95% CI -0.25 to -0.19) and ankle power (95% CI -0.89 to -0.60, were significantly lower in the Ponseti treated clubfeet compared to the healthy controls. No significant difference was found in ankle dorsiflexor and plantarflexor moment, and ankle power between clubfeet treated with surgery compared to the Ponseti method. Significance: Differences in gait kinetics are present when comparing Ponseti treated clubfeet with healthy controls. However, there is no significant difference between surgically and Ponseti treated clubfeet. These results give more insight in the possibilities of improving the gait pattern of patients treated for clubfeet.
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To study the ways in which compounds can induce adverse effects, toxicologists have been constructing Adverse Outcome Pathways (AOPs). An AOP can be considered as a pragmatic tool to capture and visualize mechanisms underlying different types of toxicity inflicted by any kind of stressor, and describes the interactions between key entities that lead to the adverse outcome on multiple biological levels of organization. The construction or optimization of an AOP is a labor intensive process, which currently depends on the manual search, collection, reviewing and synthesis of available scientific literature. This process could however be largely facilitated using Natural Language Processing (NLP) to extract information contained in scientific literature in a systematic, objective, and rapid manner that would lead to greater accuracy and reproducibility. This would support researchers to invest their expertise in the substantive assessment of the AOPs by replacing the time spent on evidence gathering by a critical review of the data extracted by NLP. As case examples, we selected two frequent adversities observed in the liver: namely, cholestasis and steatosis denoting accumulation of bile and lipid, respectively. We used deep learning language models to recognize entities of interest in text and establish causal relationships between them. We demonstrate how an NLP pipeline combining Named Entity Recognition and a simple rules-based relationship extraction model helps screen compounds related to liver adversities in the literature, but also extract mechanistic information for how such adversities develop, from the molecular to the organismal level. Finally, we provide some perspectives opened by the recent progress in Large Language Models and how these could be used in the future. We propose this work brings two main contributions: 1) a proof-of-concept that NLP can support the extraction of information from text for modern toxicology and 2) a template open-source model for recognition of toxicological entities and extraction of their relationships. All resources are openly accessible via GitHub (https://github.com/ontox-project/en-tox).
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Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
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from the article: "Abstract: The oral mucosa is the first immune tissue that encounters allergens upon ingestion of food. We hypothesized that the bio-accessibility of allergens at this stage may be a key determinant for sensitization. Light roasted peanut flour was suspended at various pH in buffers mimicking saliva. Protein concentrations and allergens profiles were determined in the supernatants. Peanut protein solubility was poor in the pH range between 3 and 6, while at a low pH (1.5) and at moderately high pHs (>8), it increased. In the pH range of saliva, between 6.5 and 8.5, the allergens Ara h2 and Ara h6 were readily released, whereas Ara h1 and Ara h3 were poorly released. Increasing the pH from 6.5 to 8.5 slightly increased the release of Ara h1 and Ara h3, but the recovery remained low (approximately 20%) compared to that of Ara h2 and Ara h6 (approximately 100% and 65%, respectively). This remarkable difference in the extraction kinetics suggests that Ara h2 and Ara h6 are the first allergens an individual is exposed to upon ingestion of peanut-containing food. We conclude that the peanut allergens Ara h2 and Ara h6 are quickly bio-accessible in the mouth, potentially explaining their extraordinary allergenicity."
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New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.
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Manure application can spread antimicrobial resistance (AMR) from manure to soil and surface water. This study evaluated the role of the soil texture on the dynamics of antimicrobial resistance genes (ARGs) in soils and surrounding surface waters. Six dairy farms with distinct soil textures (clay, sand, and peat) were sampled at different time points after the application of manure, and three representative ARGs sul1, erm(B), and tet(W) were quantified with qPCR. Manuring initially increased levels of erm(B) by 1.5 ± 0.5 log copies/kg of soil and tet(W) by 0.8 ± 0.4 log copies/kg across soil textures, after which levels gradually declined. In surface waters from clay environments, regardless of the ARG, the gene levels initially increased by 2.6 ± 1.6 log copies/L, after which levels gradually declined. The gene decay in soils was strongly dependent on the type of ARG (erm(B) < tet(W) < sul1; half-lives of 7, 11, and 75 days, respectively), while in water, the decay was primarily dependent on the soil texture adjacent to the sampled surface water (clay < peat < sand; half-lives of 2, 6, and 10 days, respectively). Finally, recovery of ARG levels was predicted after 29–42 days. The results thus showed that there was not a complete restoration of ARGs in soils between rounds of manure application. In conclusion, this study demonstrates that rather than showing similar dynamics of decay, factors such as the type of ARG and soil texture drive the ARG persistence in the environment.
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Background The plantar intrinsic foot muscles (PIFMs) have a role in dynamic functions, such as balance and propulsion, which are vital to walking. These muscles atrophy in older adults and therefore this population, which is at high risk to falling, may benefit from strengthening these muscles in order to improve or retain their gait performance. Therefore, the aim was to provide insight in the evidence for the effect of interventions anticipated to improve PIFM strength on dynamic balance control and foot function during gait in adults. Methods A systematic literature search was performed in five electronic databases. The eligibility of peer-reviewed papers, published between January 1, 2010 and July 8, 2020, reporting controlled trials and pre-post interventional studies was assessed by two reviewers independently. Results from moderate- and high-quality studies were extracted for data synthesis by summarizing the standardized mean differences (SMD). The GRADE approach was used to assess the certainty of evidence. Results Screening of 9199 records resulted in the inclusion of 11 articles of which five were included for data synthesis. Included studies were mainly performed in younger populations. Low-certainty evidence revealed the beneficial effect of PIFM strengthening exercises on vertical ground reaction force (SMD: − 0.31-0.37). Very low-certainty evidence showed that PIFM strength training improved the performance on dynamic balance testing (SMD: 0.41–1.43). There was no evidence for the effect of PIFM strengthening exercises on medial longitudinal foot arch kinematics. Conclusions This review revealed at best low-certainty evidence that PIFM strengthening exercises improve foot function during gait and very low-certainty evidence for its favorable effect on dynamic balance control. There is a need for high-quality studies that aim to investigate the effect of functional PIFM strengthening exercises in large samples of older adults. The outcome measures should be related to both fall risk and the role of the PIFMs such as propulsive forces and balance during locomotion in addition to PIFM strength measures.
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Progressive disability develops with older age in association with underlying disease, comorbidity and frailty. Physical performance characteristics are important to improve the physical condition of older persons and therefore may be able to prevent or delay the onset of (progressive) disability. However lack of understanding of the physiology and etiology of functional decline leading to disability causes a problem in the development of effective preventive interventions. The aim of the present review is to determine which physical performance characteristics are determinants of disability in the older general population.
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Background Altered muscle-tendon properties in clubfoot patients could play a role in the occurrence of a relapse and negatively affect physical functioning. However, there is a lack of literature about muscle-tendon properties of clubfoot relapse patients. Research question The aim of this study was to determine whether the muscle architecture of the medial gastrocnemius and the morphology of the Achilles tendon differ between typically developing children (TDC) and clubfoot patients with and without a relapse clubfoot and to determine the relationships between morphological and functional gait outcomes. Methods A cross-sectional study was carried out in clubfoot patients treated according to the Ponseti method and TDC aged 4–8 years. A division between clubfoot patients with and without a relapse was made. Fifteen clubfoot patients, 10 clubfoot relapse patients and 19 TDC were included in the study. Morphologic properties of the medial head of the Gastrocnemius muscle and Achilles tendon were assessed by ultrasonography. Functional gait outcomes were assessed using three-dimensional gait analysis. Mean group differences were analysed with ANOVA and non-parametric alternatives. Relationships between functional and morphologic parameters were determined for all clubfoot patients together and for TDC with Spearman’s rank correlation. Results Morphological and functional gait parameters did not differ between clubfoot patients with and without a relapse, with exception of lower maximal dorsiflexor moment in clubfoot relapse patients. Compared to TDC, clubfoot and relapse patients did show lower functional gait outcomes, as well as shorter and more pennate muscles with a longer Achilles tendon. In all clubfoot patients, this longer relative tendon was related to higher ankle power and plantarflexor moment. Significance In clubfoot and relapse patients, abnormalities in morphology did not always relate to worse functional gait outcomes. Understanding these relationships in all clubfoot patients may improve the knowledge about clubfoot and aid future treatment planning.
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