Mechanisms of cerebrospinal fluid secretion by the choroid plexus epithelium: Application to various intracranial pathologies.

The choroid plexus (CP) is a small yet highly active epithelial tissue located in the ventricles of the brain. It secretes most of the CSF that envelops the brain and spinal cord. The epithelial cells of the CP have a high fluid secretion rate and differ from many other secretory epithelia in the organization of several key ion transporters. One striking difference is the luminal location of, for example, the vital Na+-K+-ATPase. In recent years, there has been a renewed focus on the role of ion transporters in CP secretion. Several studies have indicated that increased membrane transport activity is implicated in disorders such as hydrocephalus, idiopathic intracranial hypertension, and posthemorrhagic sequelae. The importance of the CP membrane transporters in regulating the composition of the CSF has also been a focus in research in recent years, particularly as a regulator of breathing and hemodynamic parameters such as blood pressure. This review focuses on the role of the fundamental ion transporters involved in CSF secretion and its ion composition. It gives a brief overview of the established factors and controversies concerning ion transporters, and finally discusses future perspectives related to the role of these transporters in the CP epithelium.

MYC activity at enhancers drives prognostic transcriptional programs through an epigenetic switch.

The transcription factor MYC is overexpressed in most cancers, where it drives multiple hallmarks of cancer progression. MYC is known to promote oncogenic transcription by binding to active promoters. In addition, MYC has also been shown to invade distal enhancers when expressed at oncogenic levels, but this enhancer binding has been proposed to have low gene-regulatory potential. Here, we demonstrate that MYC directly regulates enhancer activity to promote cancer type-specific gene programs predictive of poor patient prognosis. MYC induces transcription of enhancer RNA through recruitment of RNA polymerase II (RNAPII), rather than regulating RNAPII pause-release, as is the case at promoters. This process is mediated by MYC-induced H3K9 demethylation and acetylation by GCN5, leading to enhancer-specific BRD4 recruitment through its bromodomains, which facilitates RNAPII recruitment. We propose that MYC drives prognostic cancer type-specific gene programs through induction of an enhancer-specific epigenetic switch, which can be targeted by BET and GCN5 inhibitors.

Morphology of the knee after guided growth using tension-band devices: a retrospective multicenter study of 222 limbs and 285 implants.

BACKGROUND AND PURPOSE: Temporary hemiepiphysiodesis by tension-band devices is commonly applied to correct angular limb deformities in children. We aimed to evaluate knee joint morphology after guided growth using these devices. PATIENTS AND METHODS: In a retrospective multicenter study we analyzed standardized anteroposterior long-leg radiographs of 222 limbs (285 implants) of patients treated by temporary hemiepiphysiodesis with either eight-Plates or FlexTacks for coronal angular deformities of the knee joint between 2013 and 2019. Femoral floor angle (FFA), femoral notch-intercondylar distance (FNID), and tibial roof angle (TRA) were measured pre- and postoperatively to assess the central knee joint morphology. Statistical exploratory analyses were performed using linear mixed models, t-tests, Wilcoxon signed-rank test, and Mann-Whitney U test. RESULTS: 217 FlexTacks (femur 106, tibia 111) in 104 children and 68 eight-Plates (femur 61, tibia 7) in 35 children were identified. Median time period under growth guidance was 11 months (range 4-42). No statistically significant change in the FFA was detected (eight-Plate: P = 0.2; FlexTack: P = 0.3). A statistically significant difference of the FNID was found in the eight-Plate group (P = 0.02), but not in the FlexTack group (P = 0.3). While TRA increased in both groups, a statistical significance was observed only in the FlexTack group (P < 0.01). CONCLUSION: We found minor but clinically irrelevant changes in knee morphology after the treatment.

Similar outcomes after anterior cruciate ligament reconstruction in paediatric and adult populations: a 1-year follow-up of 506 paediatric operations in Denmark.

PURPOSE: To present 1-year results after all paediatric anterior cruciate ligament (ACL) reconstructions in Denmark (5.9 M inhabitants) for the 10½ year period, 1 July 2011 to 31 December 2021. METHODS: All children who had an ACL reconstruction were enrolled. They were asked to complete Pedi-IKDC preoperatively and at 1-year follow-up. Independent observers performed pivot shift test and instrumented laxity assessment preoperatively and at 1-year follow-up. RESULTS: The median age of the 506 children (47.2% girls) was 14.3 years (9.3-15.9). The Pedi-IKDC score increased from preoperatively 61.6 ± 15.8 (mean ± SD) to 85.9 ± 13.0 at 1-year follow-up (p < 0.0001). There were concomitant injuries (to meniscus and/or cartilage) in 49.9%, but these children had preoperative and follow-up Pedi-IKDC scores similar to the scores for children with isolated injury to ACL (n. s.). Instrumented anterior laxity was 4.3 ± 1.4 (mean ± SD) mm preoperatively and 1.4 ± 1.4 mm at follow-up (p < 0.0001). Preoperatively, 3% had no pivot shift whilst this was the case for 68% postoperatively (p < 0.0001). Twenty-five children (5.6%) had 4 mm instrumented laxity or more relative to the unoperated knee at follow-up. Two patients (0.4%) had an operatively treated deep infection, three (0.5%) were operated on for reduced range of motion and two (0.4%) had a revision ACL reconstruction. CONCLUSION: ACL reconstruction resulted in a clinically meaningful increase in Pedi-IKDC, an improved instrumented stability, a reduction in the grade of pivot shift and the complication rate was low at 1-year follow-up. The risk of graft insufficiency at 1-year follow-up was the same as in an adult population. LEVEL OF EVIDENCE: II.

Pedi-IKDC exhibits questionable measurement properties in a cohort of pediatric patients with ACL rupture.

BACKGROUND: Pedi-IKDC is commonly used to evaluate anterior cruciate ligament (ACL) deficiency in children. However, its construct validity has not been thoroughly assessed. The aim was to examine the measurement properties of the Pediatric International Knee Documentation Committee (Pedi-IKDC) by modern test theory (MTT) models, confirmatory factor analysis (CFA), and item response theory (IRT). METHODS: The cohort consisted of all children and adolescents in Denmark (n = 535, age 9-16) treated with physeal-sparing ACL reconstruction 2011-2020. Patient-reported outcome measure (PROM) data were collected before surgery and at 1 year follow-up. Structural validity of Pedi-IKDC was assessed with MTT models. Reliability was reported as McDonalds coefficient omega. Responsiveness was evaluated with standardized response means. RESULTS: Sufficient PROM data were available for 372 patients. The original unidimensional construct did not fit CFA model expectations neither before surgery (χ2 = 462.0, df = 163, p < 0.0001; RMSEA: 0.109, CFI: 0.910, TFI: 0.895) nor at follow-up. Neither did a two-factor CFA model with "Symptoms" and "Sports activities" as individual subscales (χ2 = 455.6, df = 162, p < 0.0001) nor a bifactor model (χ2 = 338.9, df = 143, p < 0.0001), although fit indices improved with the latter (RMSEA: 0.094, CFI: 0.941, TFI: 0.922). The IRT models confirmed this pattern. The scale was responsive (SRM 1.66 (95% CI: 1.46-1.88)). Coefficient omega values were 0.866 before surgery and 0.919 at follow-up. CONCLUSIONS: The Pedi-IKDC exhibited inadequate structural validity. Neither the original construct, a two-factor model, nor bifactor models fitted data well. We advise that data obtained by Pedi-IKDC are interpreted with caution.

PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation.

Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation, and mutations that interfere with its function cause lipodystrophy. PPARγ is a highly modular protein, and structural studies indicate that PPARγ domains engage in several intra- and inter-molecular interactions. How these interactions modulate PPARγ's ability to activate target genes in a cellular context is currently poorly understood. Here we take advantage of two previously uncharacterized lipodystrophy mutations, R212Q and E379K, that are predicted to interfere with the interaction of the hinge of PPARγ with DNA and with the interaction of PPARγ ligand binding domain (LBD) with the DNA-binding domain (DBD) of the retinoid X receptor, respectively. Using biochemical and genome-wide approaches we show that these mutations impair PPARγ function on an overlapping subset of target enhancers. The hinge region-DNA interaction appears mostly important for binding and remodelling of target enhancers in inaccessible chromatin, whereas the PPARγ-LBD:RXR-DBD interface stabilizes the PPARγ:RXR:DNA ternary complex. Our data demonstrate how in-depth analyses of lipodystrophy mutants can unravel molecular mechanisms of PPARγ function.

KOOS-Child exhibits inadequate structural validity in a cohort of paediatric patients with ACL deficiency.

OBJECTIVES: Knee injury and Osteoarthritis Outcome Score (KOOS)-Child is a modification of the adult KOOS aiming to evaluate knee injury, including ACL deficiency. However, the measurement properties of KOOS-Child have not been assessed in a cohort of children with ACL deficiency. We aimed to study the structure of KOOS-Child using modern test theory models (Rasch analysis and confirmatory factor analysis (CFA)). METHODS: Data were collected prospectively in a cohort of children with ACL deficiency at three time points: before-and-after ACL surgery, and at 1-year follow-up. For each subscale, structural validity through the fit of a CFA model was evaluated for 153 respondents. Modification indices were examined to find the model of best fit, confirmed using Rasch analysis. Responsiveness was reported for each subscale. Reliability was calculated for each item. Floor and ceiling effects, and Person-item distribution were reported. RESULTS: All subscales showed inadequate fit to a unidimensional CFA model. Rasch analysis confirmed these results. Adjusting the subscales improved model fit, although this was still quite poor, except for the quality of life subscale. With one exception, all items demonstrated ceiling effects. Person-item distribution confirmed this. Due to lack of fit, reliability was not reported. All subscales were able to detect change from baseline to 1-year follow-up. CONCLUSIONS: KOOS-Child exhibits inadequate measurement properties in its current form for children with ACL deficiency. Suggestions to make the subscales fit the models better and improve accuracy of KOOS-Child are presented. However, the large ceiling effects observed may reduce sensitivity and induce type 2 errors.

How Risk Management During COVID-19 Influences Eldercare Personnel's Perceptions of Their Work Environment.

OBJECTIVE: To investigate the association between workplace COVID-19 (coronavirus disease 2019) risk management and eldercare workers' perception of their social environment at work. METHODS: Cross-sectional questionnaire data from 952 participants were collected by the Danish labor union, FOA, and analyzed using multinomial logistic regression. RESULTS: Unclear guidelines, insecurity regarding organization of work, lack of attention to vulnerable employees, and lack of instruction in the use of personal protective equipment were associated with perceived negative changes in the social environment at work. Also, higher local incidence rates of SARS-CoV-2 infections were associated with a weaker sense of community (odds ratio, 1.18; 95% confidence interval, 1.04-1.36). CONCLUSIONS: These findings indicate that risk management is important not only for prevention of infection but also for individual and workplace resilience toward external demands and health threats.

In Vivo Neutralization of Myotoxin II, a Phospholipase A2 Homologue from Bothrops asper Venom, Using Peptides Discovered via Phage Display Technology.

Many snake venom toxins cause local tissue damage in prey and victims, which constitutes an important pathology that is challenging to treat with existing antivenoms. One of the notorious toxins that causes such effects is myotoxin II present in the venom of the Central and Northern South American viper, Bothrops asper. This Lys49 PLA2 homologue is devoid of enzymatic activity and causes myotoxicity by disrupting the cell membranes of muscle tissue. To improve envenoming therapy, novel approaches are needed, warranting the discovery and development of inhibitors that target key toxins that are currently difficult to neutralize. Here, we report the identification of a new peptide (JB006), discovered using phage display technology, that is capable of binding to and neutralizing the toxic effects of myotoxin II in vitro and in vivo. Through computational modeling, we further identify hypothetical binding interactions between the toxin and the peptide to enable further development of inhibitors that can neutralize myotoxin II.

Attitudes about the treatment of obesity among healthcare providers involved in the care of obesity-related diseases: A survey across medical specialties in multiple European countries.

BACKGROUND AND RATIONALE: Obesity is associated with the development and progression of many diseases. Understanding and management of obesity have become increasingly important; however, a knowledge gap remains between how healthcare providers (HCPs) consider weight-loss treatment and the importance of weight loss for improving obesity-related diseases. OBJECTIVE: The objective of this study was to investigate how HCPs assess obesity, how they interpret the relationship between obesity and 12 recognized co-morbidities of obesity (excluding diabetes), and their view about the value of various weight-loss therapies. METHODS: This was a cross-sectional, non-interventional, descriptive study. Participants were medical doctors (HCPs) from eight European countries. RESULTS: Eighty-nine percent of the 197 HCPs that completed the survey considered obesity a disease. For most of the 12 obesity-related diseases under consideration, a majority of HCPs agreed that weight loss could reverse the disease or prevent progression. Among HCPs who have recommended weight loss, lifestyle interventions were by far the most common recommendation. However, more than three out of four HCPs stated that they would be likely to prescribe anti-obesity medications if available and reimbursed. CONCLUSION: Most HCPs in this survey consider obesity a disease that needs to be treated. However, the majority of HCPs appear to prefer recommending lifestyle changes, although it is well documented that weight loss obtained by lifestyle changes is difficult to maintain. These results underscore the need for improved education of HCPs involved in the treatment of obesity-related diseases.

Societal Costs of Moderate-to-severe Atopic Dermatitis Occurring in Adulthood: A Danish Register-based Study.

To estimate the cost of illness in adult patients with moderate-to-severe atopic dermatitis (AD) a cohort study was conducted identifying Danish citizens (≥ 18 years) diagnosed with AD between 1997 and 2018 in the Danish National Patient Register. Moderate-to-severe AD was defined as ≥3 hospital contacts regarding AD the first year after diagnosis. Each patient with AD was matched to 3 reference individuals through the Central Person Registry. Societal costs included the direct costs for primary-sector visits, inpatient hospitalizations, outpatient contacts, prescription medicine and indirect costs of lost productivity 3 years before and 5 years after the index date (the study period). A total of 5,245 patients with moderate-to-severe AD were identified. The mean attributable healthcare costs for patients with moderate-to-severe AD were EUR 10,835 (p < 0.0001) during the study period. Moderate-to-severe AD among adults inferred substantial economic burden compared with a group of matched reference individuals.

Costs of electronic health vs. standard care management of inflammatory bowel disease across three years of follow-up-a Danish register-based study.

BACKGROUND: Costs of using eHealth in inflammatory bowel disease (IBD) management has only been assessed for short follow-up periods. The primary aim was to compare the direct costs of eHealth (cases) relative to standard care (matched controls) for IBD during three years of follow-up. METHODS: The study design was a retrospective, registry-based follow-up study of patients diagnosed with IBD two years prior, and three years subsequent, to their enrolment in eHealth. Cases were matched 1:4 with controls receiving standard care based on diagnosis, gender, biologics (yes/no) and age (+/- 5 years). RESULTS: We identified 116 cases (76 (66%) with ulcerative colitis (UC) and 40 (34%) with Crohn's disease (CD)) and matched them with 433 controls. IBD-related outpatient costs were only significantly higher for cases in the year of their inclusion in eHealth (€2,949 vs. €1,621 per patient, p =.01). Mean IBD-related admission costs tended to fall after enrolment in eHealth, with mean admission costs per patient at year 3 of follow-up of €74 for cases and €383 for controls (p = .02). Linear extrapolation of the reduction in costs beyond year 3 after enrolment in eHealth revealed that eHealth would be cost neutral or saving, relative to standard care, from year 4. CONCLUSION: IBD-related outpatient costs in both groups were similar and only significantly higher for cases in the year of their enrolment in eHealth, with admission costs typically falling after a patient's inclusion in eHealth. Estimation revealed eHealth to be cost neutral or saving from year 4.

Costs of the COVID-19 pandemic associated with obesity in Europe: A health-care cost model.

Excess weight is associated with severe outcomes of coronavirus disease 2019 (COVID-19). We aimed to estimate the total secondary care costs by body mass index (BMI, kg/m2 ) category when hospitalized due to COVID-19 in Europe during the first wave of the pandemic from January to June 2020. Building a health-care cost model, this study aimed to estimate the total costs of COVID-19. Information on risk of hospitalization, admission to intensive care unit (ICU) and risk of ventilation were based on published data. Average cost per patient and in total were calculated based on risks of admission to ICU, risk of invasive mechanical ventilation and length of hospital stay when hospitalized and published costs associated with hospitalization. The total direct costs of secondary care during the first wave of COVID-19 in Europe were estimated at EUR 13.9 billon, whereof 76% accounted for treating people with overweight and obesity. The average cost per hospital admission increased with BMI, from EUR 15831 for BMI <25 kg/m2 to EUR 30982 for BMI ≥40 kg/m2 . This study reveals that excess weight contributes disproportionally to the costs of COVID-19. This might reflect that overweight and obesity caused the COVID-19 pandemic to result in more severe outcomes for citizens and higher secondary care costs throughout Europe.

COVID-19 risk management at the workplace, fear of infection and fear of transmission of infection among frontline employees.

OBJECTIVES: We compared COVID-19 risk management, fear of infection and fear of transmission of infection among frontline employees working within eldercare, hospital/rehabilitation, psychiatry, childcare and ambulance service and explored if group differences in fear of infection and transmission could be explained by differences in risk management. We also investigated the association of risk management with fear of infection and fear of transmission of infection among eldercare personnel. METHODS: We used cross-sectional questionnaire data collected by the Danish labour union, FOA . Data were collected 5½ weeks after the first case of COVID-19 was registered in Denmark. Data for the first aim included 2623 participants. Data for the second aim included 1680 participants. All independent variables were mutually adjusted and also adjusted for sex, age, job title and region. RESULTS: Fear of infection (49%) and fear of transmitting infection from work to the private sphere (68%) was most frequent in ambulance service. Fear of transmitting infection during work was most frequent in the eldercare (55%). Not all differences in fear of infection and transmission between the five areas of work were explained by differences in risk management. Among eldercare personnel, self-reported exposure to infection and lack of access to test was most consistently associated with fear of infection and fear of transmission, whereas lack of access to personal protective equipment was solely associated with fear of transmission. CONCLUSION: We have illustrated differences and similarities in COVID-19 risk management within five areas of work and provide new insights into factors associated with eldercare workers' fear of infection and fear of transmission of infection.

Costs of COVID-19 pandemic associated with diabetes in Europe: a health care cost model.

OBJECTIVE: Diabetes is associated with progression to severe COVID-19. The objective of this study was to estimate to what extent the increased risk among people with diabetes could impact the secondary care costs of COVID-19 throughout Europe during the first wave of the COVID-19 pandemic from January to June 2020. METHODS: Applying a health care cost model based on inputs from data published in international peer-reviewed journals, identified via a rapid literature review this study aimed to estimate the total secondary sector costs of COVID-19. Estimates of unit costs were based on data from Denmark, France, Spain and the UK. We calculated average costs per patient without diabetes and according to four diabetes categories based on risk of hospitalization, admission to intensive care unit, ventilator support and length of hospital stay. RESULTS: The estimated cost per hospital admission during the first wave of COVID-19 in Europe ranged between EUR 25,018 among people with type 2 diabetes in good glycaemic control to EUR 57,244 among people with type 1 diabetes in poor glycaemic control, reflecting higher risk of intensive care, ventilator support and longer hospital stay according to diabetes category, while the corresponding cost for people without diabetes was estimated at EUR 16,993. The total direct costs of secondary care of COVID-19 in Europe were estimated at EUR 13.9 billion. Thus, 23.5% of the total costs accounted for treating people with diabetes. CONCLUSIONS: This study highlights the importance of a greater focus on prevention and adequate treatment of diabetes and the need for special attention to avoid infection with COVID-19 to the extent possible among those already diagnosed with diabetes.

Peptide Inhibitors of the α-Cobratoxin-Nicotinic Acetylcholine Receptor Interaction.

Venomous snakebites cause >100 000 deaths every year, in many cases via potent depression of human neuromuscular signaling by snake α-neurotoxins. Emergency therapy still relies on antibody-based antivenom, hampered by poor access, frequent adverse reactions, and cumbersome production/purification. Combining high-throughput discovery and subsequent structure-function characterization, we present simple peptides that bind α-cobratoxin (α-Cbtx) and prevent its inhibition of nicotinic acetylcholine receptors (nAChRs) as a lead for the development of alternative antivenoms. Candidate peptides were identified by phage display and deep sequencing, and hits were characterized by electrophysiological recordings, leading to an 8-mer peptide that prevented α-Cbtx inhibition of nAChRs. We also solved the peptide:α-Cbtx cocrystal structure, revealing that the peptide, although of unique primary sequence, binds to α-Cbtx by mimicking structural features of the nAChR binding pocket. This demonstrates the potential of small peptides to neutralize lethal snake toxins in vitro, establishing a potential route to simple, synthetic, low-cost antivenoms.

Highly interconnected enhancer communities control lineage-determining genes in human mesenchymal stem cells.

Adipocyte differentiation is driven by waves of transcriptional regulators that reprogram the enhancer landscape and change the wiring of the promoter interactome. Here, we use high-throughput chromosome conformation enhancer capture to interrogate the role of enhancer-to-enhancer interactions during differentiation of human mesenchymal stem cells. We find that enhancers form an elaborate network that is dynamic during differentiation and coupled with changes in enhancer activity. Transcription factors (TFs) at baited enhancers amplify TF binding at target enhancers, a phenomenon we term cross-interaction stabilization of TFs. Moreover, highly interconnected enhancers (HICE) act as integration hubs orchestrating differentiation by the formation of three-dimensional enhancer communities, inside which, HICE, and other enhancers, converge on phenotypically important gene promoters. Collectively, these results indicate that enhancer interactions play a key role in the regulation of enhancer function, and that HICE are important for both signal integration and compartmentalization of the genome.

Correlations of fatigue in Danish patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis.

OBJECTIVE: To describe fatigue in relation to disease-specific and socioeconomic factors and to test possible correlations between fatigue and work impairment, quality of life, pain, sleep, depression, and physical functioning in people with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: A questionnaire-based cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and patient-reported outcomes (PROs) from patients with RA, PsA and axSpA in Denmark. PRO scales included the FACIT-Fatigue sub-scale, Work Productivity and Activity Impairment scale (WPAI), EuroQol (EQ-5D), Medical Outcomes Study Sleep Scale (MOS), Major Depression Inventory (MDI), and Health Assessment Questionnaire (HAQ). Respondents were recruited via routine visits to the outpatient rheumatology clinic; information on diagnosis, treatment and disease activity was collected from medical journals by trained nurses. RESULTS: 487 patients participated in the study. Fatigue was more present in women, experienced patients, and patients who changed medication in the past 12 months, who were unemployed, who had less education, and who had lower household income. There was no statistically significant difference between mean fatigue in the three diagnostic groups (p = 0.08). Fatigue correlated with all included PROs (Pearson correlation coefficients, p<0.0001). Stratifying for diagnosis and adjusting for socioeconomic factors did not change the conclusion. CONCLUSION: In a stable, representative group of patients with RA, PsA and axSpA, we found significant correlations between fatigue and work impairment, quality of life, pain, sleep, depression and physical functioning. Fatigue cannot be perceived as a single problem, but rather as a symptom that affects broadly.

ERASSTRI - European Risk Assessment Study on Synthetic Turf Rubber Infill - Part 1: Analysis of infill samples.

End-of-life tyre (ELT)-derived rubber granules are used as synthetic turf infill on sports fields. They contain various chemical substances and there are concerns that exposure to these substances might be harmful for human health. This Europe-wide risk assessment study addresses these concerns. As the first part, chemical substances in samples from recycling companies and from sports fields were analysed. 86 coated and non-coated ELT granule samples from sites in 14 European countries were investigated, together with ten non-ELT materials. An extensive list of potentially relevant substances was compiled, and the infill materials were analysed for these substances, using GC and HPLC methods. Volatilisation of substances was studied in emission chambers. Polycyclic aromatic hydrocarbons (sum of 8 REACH PAHs) were identified at average concentrations below 10 mg/kg. Substances found at higher concentrations in rubber granules were aluminium (arithmetic mean in uncoated samples from sports fields 5383 mg/kg) and cobalt (168 mg/kg), benzothiazole (48 mg/kg) and 2-hydroxybenzothiazole (34 mg/kg), 6PPD (571 mg/kg) and DPG (51 mg/kg), and 4-tert-octylphenol (14 mg/kg). In addition, the following volatiles were found to evaporate from crumb rubber in emission chambers: benzothiazole, tert-butylamine, cyclohexanone, methyl isobutyl ketone, 2-heptanone and saturated aliphatic hydrocarbons higher than C9. With this comprehensive survey we created a profound database on concentrations of chemical substances in ELT-derived infill material, which is essential for a reliable risk assessment. The results were used to inform subsequent investigations (migration studies, exposure monitoring survey).