Plant-based food contact materials: presence of hazardous substances.

As a result of the European Single Use Plastic Directive and as part of the transition to a circular economy, plastic food contact materials (FCMs) are being replaced, often by renewable plant-based materials. This research aimed to identify which chemical substances are present in plant-based materials. In 2022 a total of 28 samples of the latter materials from the Dutch market were analysed for 313 active substances from plant protection products, 47 per- and polyfluoralkyl substances (PFASs) and 27 heavy metals and other elements. Ten samples contained plant protection products that are not authorised in the EU. Most materials contained PFASs at trace or even high levels. Three out of four investigated sugar cane materials contained 6:2 fluorotelomer alcohol at levels up to 1.7 mg/kg. High contents of aluminium, manganese, iron, zinc, and barium were found. Other heavy metals, such as arsenic, lead and mercury were found in relatively low contents. A broad GC-MS screening was performed, which revealed the presence of plant extractable, plasticisers, antioxidants and hydrocarbons, which were not all authorised for FCMs, but may be present as non-intentionally added substances.

Opportunities for Regulatory Authorities to Assess Animal-Based Measures at the Slaughterhouse Using Sensor Technology and Artificial Intelligence: A Review.

Animal-based measures (ABMs) are the preferred way to assess animal welfare. However, manual scoring of ABMs is very time-consuming during the meat inspection. Automatic scoring by using sensor technology and artificial intelligence (AI) may bring a solution. Based on review papers an overview was made of ABMs recorded at the slaughterhouse for poultry, pigs and cattle and applications of sensor technology to measure the identified ABMs. Also, relevant legislation and work instructions of the Dutch Regulatory Authority (RA) were scanned on applied ABMs. Applications of sensor technology in a research setting, on farm or at the slaughterhouse were reported for 10 of the 37 ABMs identified for poultry, 4 of 32 for cattle and 13 of 41 for pigs. Several applications are related to aspects of meat inspection. However, by European law meat inspection must be performed by an official veterinarian, although there are exceptions for the post mortem inspection of poultry. The examples in this study show that there are opportunities for using sensor technology by the RA to support the inspection and to give more insight into animal welfare risks. The lack of external validation for multiple commercially available systems is a point of attention.

Mixture effects of tetrodotoxin (TTX) and drugs targeting voltage-gated sodium channels on spontaneous neuronal activity in vitro.

Tetrodotoxin (TTX) potently inhibits TTX-sensitive voltage-gated sodium (NaV) channels in nerve and muscle cells, potentially resulting in depressed neurotransmission, paralysis and death from respiratory failure. Since a wide range of pharmaceutical drugs is known to also act on NaV channels, the use of medicines could predispose individuals to a higher susceptibility towards TTX toxicity. We therefore first assessed the inhibitory effect of selected medicines that act on TTX-sensitive (Riluzole, Chloroquine, Fluoxetine, Valproic acid, Lamotrigine, Lidocaine) and TTX-resistant (Carbamazepine, Mexiletine, Flecainide) NaV channels on spontaneous neuronal activity of rat primary cortical cultures grown on microelectrode arrays (MEA). After establishing concentration-effect curves, binary mixtures of the medicines with TTX at calculated NOEC, IC20 and IC50 values were used to determine if pharmacodynamic interactions occur between TTX and these drugs on spontaneous neuronal activity. At IC20 and IC50 values, all medicines significantly increased the inhibitory effect of TTX on spontaneous neuronal activity of rat cortical cells in vitro. Subsequent experiments using human iPSC-derived neuronal co-cultures grown on MEAs confirmed the ability of selected medicines (Carbamazepine, Flecainide, Riluzole, Lidocaine) to inhibit spontaneous neuronal activity. Despite the need for additional experiments using human iPSC-derived neuronal co-cultures, our combined data already highlight the importance of identifying and including vulnerable risk groups in the risk assessment of TTX.

Current approaches and challenges of sample preparation procedures for the safety assessment of paper and cardboard food contact materials: A comprehensive review.

In the European Union (EU), Regulation (EC) 1935/2004 provides a harmonized legal EU framework and sets out the general principles for safety and inertness for all Food Contact Materials (FCMs) and Food Contact Articles. From a food safety point of view, however, specific EU legislation for paper and cardboard FCMs is lacking, while at Member State level, national legislation differs among countries. More than 11,000 chemicals have been identified in all types of FCMs, most of them without any information on toxicity or migration potential from FCM to food. The present review shows a wide variability of protocols, approaches, and conditions used in scientific studies, which are difficult to compare. In this regard, procedures and conditions laid down in EU legislation for plastics and European Standards (EN protocols) may serve as a good basis for the future sample preparation procedures in the framework of paper and cardboard FCMs safety assessment. Challenges on sample preparation procedures are presented involving the interlinked steps of sample preparation, conditions used and their impact in chemical analysis and in vitro bioassay testing. Currently, there is no general consensus on the criteria for structuring, evaluating, and tuning sample preparation procedures for paper and cardboard FCMs. For this purpose, a set of modified criteria and a decision tree are proposed based on the literature. Along this, mass transfer processes occurring in paper and cardboard FCMs and parameters affecting chemical migration need to be accounted for prior to reaching general consensus on criteria for sample preparation procedures.

Enhancing the use of exposure science across EU chemical policies as part of the European Exposure Science Strategy 2020-2030.

BACKGROUND: A scientific framework on exposure science will boost the multiuse of exposure knowledge across EU chemicals-related policies and improve risk assessment, risk management and communication across EU safety, security and sustainability domains. OBJECTIVE: To stimulate public and private actors to align and strengthen the cross-policy adoption of exposure assessment data, methods and tools across EU legislation. METHODS: By mapping and analysing the EU regulatory landscape making use of exposure information, policy and research challenges and key areas of action are identified and translated into opportunities enhancing policy and scientific efficiency. RESULTS: Identified key areas of actions are to develop a common scientific exposure assessment framework, supported by baseline acceptance criteria and a shared knowledge base enhancing exchangeability and acceptability of exposure knowledge within and across EU chemicals-related policies. Furthermore, such framework will improve communication and management across EU chemical safety, security and sustainability policies comprising sourcing, manufacturing and global trade of goods and waste management. In support of building such a common framework and its effective use in policy and industry, exposure science innovation needs to be better embedded along the whole policymaking cycle, and be integrated into companies' safety and sustainability management systems. This will help to systemically improve regulatory risk management practices. SIGNIFICANCE: This paper constitutes an important step towards the implementation of the EU Green Deal and its underlying policy strategies, such as the Chemicals Strategy for Sustainability.

COVID outcome prediction in the emergency department (COPE): using retrospective Dutch hospital data to develop simple and valid models for predicting mortality and need for intensive care unit admission in patients who present at the emergency department with suspected COVID-19.

OBJECTIVES: Develop simple and valid models for predicting mortality and need for intensive care unit (ICU) admission in patients who present at the emergency department (ED) with suspected COVID-19. DESIGN: Retrospective. SETTING: Secondary care in four large Dutch hospitals. PARTICIPANTS: Patients who presented at the ED and were admitted to hospital with suspected COVID-19. We used 5831 first-wave patients who presented between March and August 2020 for model development and 3252 second-wave patients who presented between September and December 2020 for model validation. OUTCOME MEASURES: We developed separate logistic regression models for in-hospital death and for need for ICU admission, both within 28 days after hospital admission. Based on prior literature, we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. We assessed model performance by the area under the receiver operating characteristic curve (AUC) and by calibration plots. RESULTS: Of 5831 first-wave patients, 629 (10.8%) died within 28 days after admission. ICU admission was fully recorded for 2633 first-wave patients in 2 hospitals, with 214 (8.1%) ICU admissions within 28 days. A simple model-COVID outcome prediction in the emergency department (COPE)-with age, respiratory rate, C reactive protein, lactate dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well calibrated and showed good discrimination for mortality in second-wave patients (AUC in four hospitals: 0.82 (95% CI 0.78 to 0.86); 0.82 (95% CI 0.74 to 0.90); 0.79 (95% CI 0.70 to 0.88); 0.83 (95% CI 0.79 to 0.86)). COPE was also able to identify patients at high risk of needing ICU admission in second-wave patients (AUC in two hospitals: 0.84 (95% CI 0.78 to 0.90); 0.81 (95% CI 0.66 to 0.95)). CONCLUSIONS: COPE is a simple tool that is well able to predict mortality and need for ICU admission in patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making.

Acute Effects of Dietary Nitrate on Exercise Tolerance, Muscle Oxygenation, and Cardiovascular Function in Patients With Peripheral Arterial Disease.

Previous studies have used supplements to increase dietary nitrate intake in clinical populations. Little is known about whether effects can also be induced through vegetable consumption. Therefore, the aim of this study was to assess the impact of dietary nitrate, through nitrate-rich vegetables (NRV) and beetroot juice (BRJ) supplementation, on plasma nitrate and nitrite concentrations, exercise tolerance, muscle oxygenation, and cardiovascular function in patients with peripheral arterial disease. In a randomized crossover design, 18 patients with peripheral arterial disease (age: 73 ± 8 years) followed a nitrate intake protocol (∼6.5 mmol) through the consumption of NRV, BRJ, and nitrate-depleted BRJ (placebo). Blood samples were taken, blood pressure and arterial stiffness were measured in fasted state and 150 min after intervention. Each intervention was followed by a maximal walking exercise test to determine claudication onset time and peak walking time. Gastrocnemius oxygenation was measured by near-infrared spectroscopy. Blood samples were taken and blood pressure was measured 10 min after exercise. Mean plasma nitrate and nitrite concentrations increased (nitrate; Time × Intervention interaction; p < .001), with the highest concentrations after BRJ (494 ± 110 µmol/L) compared with NRV (202 ± 89 µmol/L) and placebo (80 ± 19 µmol/L; p < .001). Mean claudication onset time and peak walking time did not differ between NRV (413 ± 187 s and 745 ± 220 s, respectively), BRJ (392 ± 154 s and 746 ± 176 s), and placebo (403 ± 176 s and 696 ± 222 s) (p = .762 and p = .165, respectively). Gastrocnemius oxygenation, blood pressure, and arterial stiffness were not affected by the intervention. NRV and BRJ intake markedly increase plasma nitrate and nitrite, but this does not translate to improved exercise tolerance, muscle oxygenation, and/or cardiovascular function.

Investigation of oral atopic diseases: Correlation between geographic tongue and fungiform papillary glossitis.

INTRODUCTION: The correlation between oral lesions and atopy is not new, but few studies have investigated the prevalence of mucosal changes in diseases within the atopic spectrum, leading to conflicting data. Some studies found a possible relationship between geographic tongue, transient lingual papillitis and atopic diseases. AIM: To investigate the frequency of geographic tongue and fungiform papillary glossitis in patients with atopic diseases, and its correlation with serum IgE levels and skin test results. MATERIAL AND METHODS: The sample was comprised of participants with atopic diseases paired with participants who received negative puncture skin tests. All were submitted to stomatological and medical evaluations, prick test and oral cytopathological. RESULTS: The female sex was more numerous in both groups. Mean age was 21 years. A total of 60 diagnoses of atopic diseases were obtained, with allergic rhinitis being the most prevalent. Fungiform papillary glossitis was the most frequent oral lesion in both groups, while geographic tongue was present in 2 cases (2%) in the test group and 2 (2%) in the control group. Atopic patients with fungiform papillary glossitis presented high serum IgE levels. In atopic patients with geographic tongue, the prick test positively identified extracts of Dermatophagoides pteronyssinus (100%) and Dermatophagoides farinae (100%). CONCLUSION: Due to the low frequency of geographic tongue lesions found in the study, it is no possible to conclude if that could be an oral manifestation of atopy. However fungiform papillary glossitis is a common alteration in atopic and non-atopic patients and has a relationship with high IgE serum levels. However, the consolidation of this result requires a larger sample size.

Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System.

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

Ultrasound imaging links soleus muscle neuromechanics and energetics during human walking with elastic ankle exoskeletons.

Unpowered exoskeletons with springs in parallel to human plantar flexor muscle-tendons can reduce the metabolic cost of walking. We used ultrasound imaging to look 'under the skin' and measure how exoskeleton stiffness alters soleus muscle contractile dynamics and shapes the user's metabolic rate during walking. Eleven participants (4F, 7M; age: 27.7 ± 3.3 years) walked on a treadmill at 1.25 m s-1 and 0% grade with elastic ankle exoskeletons (rotational stiffness: 0-250 Nm rad-1) in one training and two testing days. Metabolic savings were maximized (4.2%) at a stiffness of 50 Nm rad-1. As exoskeleton stiffness increased, the soleus muscle operated at longer lengths and improved economy (force/activation) during early stance, but this benefit was offset by faster shortening velocity and poorer economy in late stance. Changes in soleus activation rate correlated with changes in users' metabolic rate (p = 0.038, R2 = 0.44), highlighting a crucial link between muscle neuromechanics and exoskeleton performance; perhaps informing future 'muscle-in-the loop' exoskeleton controllers designed to steer contractile dynamics toward more economical force production.

A health risk for consumers: the presence of adulterated food supplements in the Netherlands.

The use of food supplements is increasing. They are marketed as beneficial for health, well-being, physical or mental condition and performance, or to prevent diseases. Producers add synthetic compounds or illicit herbal material to food supplements to claim desired effects. Claims made to support marketing without scientific evidence are, however, illegal. Intake of adulterated food supplements may lead to serious adverse effects. The aim of this paper is to report the results of analyses of (adulterated) food supplements conducted by the Netherlands Food and Consumer Product Safety Authority between October 2013 and October 2018. In total, 416 supplements were analysed of which 264 (64%) contained one or more pharmacological active substances or plant toxins, such as caffeine, synephrine, sildenafil, icariin, sibutramine, higenamine, hordenine, phenethylamine, methylsynephrine, DMAA, phenolphthalein, octopamine and ephedrine. When compared to dose levels that are considered safe, daily doses of the substances in the food supplements were sometimes much higher, causing a risk for consumers who are unaware of the presence of these pharmacologically active substances. In many cases, neither food nor medicines legislation (easily) enables enforcement actions. This means that some products containing pharmacologically active substances (i.e. synthetic medicines and their illicit analogues), stay available on the market. An undesirable situation because for many of these substances no detailed toxicity data are available.

Truck safety evaluation on Wyoming mountain passes.

The Manual on Uniform Traffic Control Devices (MUTCD) for Streets and Highways recommends hill signs be placed in advance of downgrade descent of mountain passes. Mountain passes increase the risk of a runaway, or out of control trucks and so the advance warning signs inform the driver to take special precautions such as reducing speed or using lower gears during the descent. The Wyoming Department of Transportation has installed steep grade advance warning systems on Wyoming mountain passes. However, concerns for out of control trucks on the mountain passes persist. The objective of this study is to evaluate the safety effectiveness of steep grade advance warning signs for trucks on Wyoming mountain passes. The safety evaluation was carried out by implementing a zero-inflated negative binomial modeling technique for predicting truck crashes on mountain passes. The outcome was two models that showed the risk of runaway truck accidents were high at locations where either the grades were steep and long or the grades were long with multiple vertical curves. The analysis showed the current advance warning systems were not significantly impacting truck crash risks at the high risk locations. The study, therefore, recommends some improvements to the current advanced warning signs or implementing an improved Federal Highway Administration Grade Severity Rating System based warning system that will significantly improve truck safety at the hazardous locations. The study informs policy makers on the safety issues on Wyoming Mountain passes with regards to runaway trucks and makes recommendations for reducing the risk of runaway truck crashes on mountain passes.

Facts and challenges in respiratory neurobiology.

Respiratory neurobiology has been a lead discipline in the field of neuroscience for almost a century. Despite this, research studies on the fundamental synaptic and cellular processes underlying the generation and modulation of breathing movements suffered a significant decline during the last decade. We still believe that respiratory neurobiology is one of the most exciting and imperative fields of neuroscience. With the first white paper concerned with the central control of breathing, we want to celebrate the global importance of breathing research.

In situ synthesis and characterization of hydroxyapatite/natural rubber composites for biomedical applications.

In this work, a biomimetic synthesis reaction for the production of hydroxyapatite (HA)/natural rubber (NR) composites is presented. HA was synthesized in the presence of solubilized NR in tetrahydrofuran (THF), which permits that negatively charged domains in proteins and lipids in NR work as nucleation sites for hydroxyapatite. The mechanical and physicochemical properties of composites containing 10, 20 and 30wt% HA were studied. NR influenced HA crystallite morphology, shape and size and was able to disperse the HA particles in THF. The dispersion of HA in the composites promoted the enhancement of mechanical properties and loss of solubility of composites, which is believed to be macroscopic manifestations of the physical adsorption of NR to HA particles, known as the bound rubber phenomenon. Preliminary cell studies indicated that HepG2 cells presented viabilities ranging from 71.6 to 91.3%, with cell proliferation positively influenced by HA content at shorter culture times. The good dispersion of HA in the composites is expected to improve NR bioactivity and direct its use towards bone applications.

Ultrafast Two-Electron Transfer in a CdS Quantum Dot-Extended-Viologen Cyclophane Complex.

Time-resolved optical spectroscopies reveal multielectron transfer from the biexcitonic state of a CdS quantum dot to an adsorbed tetracationic compound cyclobis(4,4'-(1,4-phenylene) bipyridin-1-ium-1,4-phenylene-bis(methylene)) (ExBox(4+)) to form both the ExBox(3+•) and the doubly reduced ExBox(2(+•)) states from a single laser pulse. Electron transfer in the single-exciton regime occurs in 1 ps. At higher excitation powers the second electron transfer takes ∼5 ps, which leads to a mixture of redox states of the acceptor ligand. The doubly reduced ExBox(2(+•)) state has a lifetime of ∼10 ns, while CdS(+•):ExBox(3+•) recombines with multiple time constants, the longest of which is ∼300 µs. The long-lived charge separation and ability to accumulate multiple charges on ExBox(4+) demonstrate the potential of the CdS:ExBox(4+) complex to serve as a platform for two-electron photocatalysis.

Blockade of dorsolateral pontine 5HT1A receptors destabilizes the respiratory rhythm in C57BL6/J wild-type mice.

The neurotransmitter serotonin (5HT) acting via 5HT1a receptors (5HT1aR) is a potent determinant of respiratory rhythm variability. Here, we address the 5HT1aR-dependent control of respiratory rhythm variability in C57BL6/J mice. Using the in situ perfused preparation, we compared the effects of systemic versus focal blockade of 5HT1aRs. Blocking 5HT1aRs in the Kölliker-Fuse nucleus (KFn) increased the occurrence of spontaneous apneas and accounted for the systemic effects of 5HT1aR antagonists. Further, 5HT1aRs of the KFn stabilized the respiratory rhythm's response to arterial chemoreflex perturbations; reducing the recovering time, e.g., the latency to return to the baseline pattern. Together, these results suggest that the KFn regulates both intrinsic and sensory determinants of respiratory rhythm variability.

Residency and movement patterns of Arctic charr Salvelinus alpinus relative to major estuaries.

Estuarine residency and marine movements of 43 anadromous Arctic charr Salvelinus alpinus (mean ± s.d. fork length = 523 ± 97 mm) were examined using acoustic tracking in inner Frobisher Bay (IFB; 63° N; 68° W), Canada, from July to September 2008 and 2009. A mean ± s.d. migration duration of 63 ± 7 days occurred from late June to early September. Detected S. alpinus were either continuously (maximum 34 days) or intermittently present in estuarine zones, on average residing approximately one third of time tracked and returning once every 9 days. Significantly higher estuarine residency during the final 15 migration days suggested that a transition phase may occur prior to freshwater re-entry. Low travel rates during flood tide suggested individuals staged before accessing intertidal and estuarine zones. Although the two main estuaries were c. 22 km apart, 19% of tagged individuals used both. Individuals remained relatively close to freshwater overwintering systems, although late-migration inter-estuarine movements may have indicated natal homing. Approximately half of the individuals exhibited extra-estuarine travel, mostly during mid-migration, but remained within 3 km of shore ranging < 30 km straight line distance (SLD) of either estuary. It was concluded that IFB S. alpinus (1) spent a significant portion of their migration within or adjacent to the estuaries and (2) had a restricted marine distribution within 30 km SLD of the river mouths.

The association between cardiorespiratory fitness and abdominal adiposity in postmenopausal, physically inactive South Asian women.

In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8-21.8 mL/kg/min), women in the highest tertile (25.0-27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05). We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women.

Photoinduced electron transfer within a zinc porphyrin-cyclobis(paraquat-p-phenylene) donor-acceptor dyad.

Understanding the mechanism of efficient photoinduced electron-transfer processes is essential for developing molecular systems for artificial photosynthesis. Towards this goal, we describe the synthesis of a donor-acceptor dyad comprising a zinc porphyrin donor and a tetracationic cyclobis(paraquat-p-phenylene) (CBPQT(4+) ) acceptor. The X-ray crystal structure of the dyad reveals the formation of a dimeric motif through the intermolecular coordination between the triazole nitrogen and the central Zn metal of two adjacent units of the dyad. Photoinduced electron transfer within the dyad in MeCN was investigated by femtosecond and nanosecond transient absorption spectroscopy, as well as by transient EPR spectroscopy. Photoexcitation of the dyad produced a weakly coupled ZnP(+.) -CBPQT(3+.) spin-correlated radical-ion pair having a τ=146 ns lifetime and a spin-spin exchange interaction of only 0.23 mT. The long radical-ion-pair lifetime results from weak donor-acceptor electronic coupling as a consequence of having nine bonds between the donor and the acceptor, and the reduction in reorganization energy for electron transfer caused by charge dispersal over both paraquat units within CBPQT(3+.) .