Health effects of railway-induced vibration combined with railway noise - A systematic review with exposure-effect curves.

BACKGROUND: The combined health impact of concurrent railway noise and railway vibration exposure is not yet well understood. OBJECTIVES: This systematic review gives an overview of epidemiological studies on health effects from railway vibration, aiming to quantify this association with exposure-effect curves. Moreover, the combined health effects of vibration and concurrent noise were investigated. METHODS: We converted the vibration metric to an equivalent noise level and calculated an overall noise level by energetically summing the equivalent and railway noise level. The combined health effect was determined by using published evidence-based exposure-effect formulas. RESULTS: Studies included in this systematic review predominately investigated annoyance and self-reported sleep disturbances; no studies on manifest diseases were identified. For the combined effects of vibration and noise on "total" annoyance, the results based on the pooled analysis of CargoVibes project are recommended as conservative approach. DISCUSSION: Converting railway vibration into equivalent noise levels in dB may offer a pragmatic approach to assess the combined health effects of railway noise and railway vibration exposure. Future studies should include cardiovascular and mental diseases in addition to vibration-induced annoyance and sleep disturbances. Furthermore, future studies should include in-depth investigations of the interaction between railway noise and railway vibration to allow for a more accurate assessment of the railway-induced burden of disease.

Assessment of serum total 25-hydroxyvitamin D assays for Vitamin D External Quality Assessment Scheme (DEQAS) materials distributed at ambient and frozen conditions.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 2 ligand binding assays - impact of 25-hydroxyvitamin D2 and 24R,25-dihydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH)2D3. The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH)2D3 content using results from a reference measurement procedure.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

[Effects of Noise Protection Measures on Annoyance, Sleep Disorders, and Cardiovascular Diseases: A Model Calculation]. / Auswirkungen lärmmindernder Maßnahmen auf die Häufigkeit von Lärmbelästigung, Schlafstörungen und Herz-Kreislauf-Erkrankungen ­ eine Modellrechnung.

AIM: In Germany, traffic noise-related threshold values are currently set at 70 decibels (dB) during the day and 60 dB at night. According to recent study results, these threshold values might not sufficiently protect against disease risks. The model calculation presented here aimed to estimate the effects of 3 specific noise-protection measures on annoyance, sleep disorders, and cardiovascular diseases. METHODS: For road traffic noise and railway noise, 3 noise reduction approaches were modeled: (1) weighted 24 hours noise levels (LDEN) of at most 65 dB, and nightly sound pressure levels (LNight) of 55 dB; (2) LDEN of at most 60 dB and LNight of 50 dB; and (3) a general reduction of road and railway noise pressure levels by 3 dB. As an example, the effects of approaches (1) to (3) were determined for the study population of the NORAH study on disease risks (Rhine-Main area). The health consequences were estimated based on the results of the WHO Noise Guidelines (2018) and the NORAH study on disease risks. RESULTS: The model calculations showed that noise protection approach (1) could reduce the number of people suffering from sleep disturbances as a result of nightly traffic noise and of those highly annoyed as well as the number of people suffering from traffic-related cardiovascular disease by 5 to 10%. Noise protection approach (2) could reduce traffic-related cardiovascular diseases by at least about 10%; according to the WHO Noise Guidelines, it would even be possible to reduce road traffic noise-related ischemic heart disease by more than 30%. All of these measures would be of particular benefit to the highly exposed population - an already vulnerable group due to their limited socio-economic resources. With the general reduction of traffic noise pressure levels by 3 dB, the incidence of annoyance, sleep disturbances and cardiovascular diseases could be reduced particularly among those exposed to low to medium noise pressure levels. CONCLUSIONS: Considering the different objectives and target groups of the investigated noise protection measures, the introduction and implementation of specific threshold values should be supplemented by general noise reduction measures in the range below the threshold values.

LifeTime and improving European healthcare through cell-based interceptive medicine.

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.

Murine Mesenchymal Stromal Cells Retain Biased Differentiation Plasticity Towards Their Tissue of Origin.

Mesenchymal stromal/stem cells (MSCs) reside in many human tissues and comprise a heterogeneous population of cells with self-renewal and multi-lineage differentiation potential, making them useful in regenerative medicine. It remains inconclusive whether MSCs isolated from different tissue sources exhibit variations in biological features. In this study, we derived MSCs from adipose tissue (AT-MSC) and compact bone (CB-MSC). We found that early passage of MSCs was readily expandable ex vivo, whereas the prolonged culture of MSCs showed alteration of cell morphology to fibroblastoid and reduced proliferation. CB-MSCs and AT-MSCs at passage 3 were CD29+, CD44+, CD105+, CD106+, and Sca-1+; however, passage 7 MSCs showed a reduction of MSC markers, indicating loss of stem cell population after prolonged culturing. Strikingly, CB-MSC was found more efficient at undergoing osteogenic differentiation, while AT-MSC was more efficient to differentiate into adipocytes. The biased differentiation pattern of MSCs from adipogenic or osteogenic tissue source was accompanied by preferential expression of the corresponding lineage marker genes. Interestingly, CB-MSCs treated with DNA demethylation agent 5-azacytidine showed enhanced osteogenic and adipogenic differentiation, whereas the treated AT-MSCs are less competent to differentiate. Our results suggest that the epigenetic state of MSCs is associated with the biased differentiation plasticity towards its tissue of origin, proposing a mechanism related to the retention of epigenetic memory. These findings facilitate the selection of optimal tissue sources of MSCs and the ex vivo expansion period for therapeutic applications.

The permeation barrier of plant cuticles: uptake of active ingredients is limited by very long-chain aliphatic rather than cyclic wax compounds.

BACKGROUND: The barrier to diffusion of organic solutes across the plant cuticle is composed of waxes consisting of very long-chain aliphatic (VLCA) and, to varying degrees, cyclic compounds like pentacyclic triterpenoids. The roles of both fractions in controlling cuticular penetration by organic solutes, e.g. the active ingredients (AI) of pesticides, are unknown to date. We studied the permeability of isolated leaf cuticular membranes from Garcinia xanthochymus and Prunus laurocerasus for lipophilic azoxystrobin and theobromine as model compounds for hydrophilic AIs. RESULTS: The wax of P. laurocerasus consists of VLCA (12%) and cyclic compounds (88%), whereas VLCAs make up 97% of the wax of G. xanthochymus. We show that treating isolated cuticles with methanol almost quantitatively releases the cyclic fraction while leaving the VLCA fraction essentially intact. All VLCAs were subsequently removed using chloroform. In both species, the permeance of the two model compounds did not change significantly after methanol treatment, whereas chloroform extraction had a large effect on organic solute permeability. CONCLUSION: The VLCA wax fraction makes up the permeability barrier for organic solutes, whereas cyclic compounds even in high amounts have a negligible role. This is of significance when optimizing the foliar uptake of pesticides. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The Mode of Action of Adjuvants-Relevance of Physicochemical Properties for Effects on the Foliar Application, Cuticular Permeability, and Greenhouse Performance of Pinoxaden.

We comprehensively studied the complexity of the mode of action of adjuvants by uncoupling the parameters contributing to the spray process during foliar application of agrochemicals. The ethoxylated sorbitan esters Tween 20 and Tween 80 improved the efficiency of pinoxaden (PXD) in controlling grass-weed species in greenhouse experiments by aiding retention, having humectant properties, maintaining the bioavailability, and increasing the cuticular penetration of PXD. The nonethoxylated sorbitan esters Span 20 and Span 80 showed minimal effects on retention, droplet hydration, or cuticular penetration, resulting in reduced PXD effects in the greenhouse. Tris(2-ethylhexyl)phosphate (TEHP) does not contribute much to retention and spreading but strongly enhances the diffusion of PXD across isolated P. laurocerasus cuticular membranes. As TEHP was most efficient in controlling the growth of grass-weed species, we propose that the direct effect of penetration aids on cuticular permeation plays a key role in the efficiency of foliar-applied agrochemicals.

Water Sorption Isotherms of Surfactants: A Tool To Evaluate Humectancy.

Fundamental experimental data for moisture absorption of non-ionic polydisperse surfactants with differing ethylene oxide (EO) content and variable aliphatic portions were measured at relative humidities between 0 and 95% at 25 °C. Remarkable differences in moisture absorption were observed between surfactant classes but also within one series of surfactants differing in either EO content or the long-chain aliphatic fraction. Both the EO units as well as the entire molecular structure, including also the lipophilic domain, were discussed to account for the humectant activity of surfactants. Water sorption isotherms showed an exponential shape, which was argued to be associated with the formation of a "free" water domain. These humectant properties might be relevant to the behavior of a foliar-applied spray droplet of agrochemical formulation products because the uptake of active ingredients will be enhanced as a result of deferred crystal precipitation.

Aqueous pathways dominate permeation of solutes across Pisum sativum seed coats and mediate solute transport via diffusion and bulk flow of water.

The permeability of seed coats to solutes either of biological or anthropogenic origin plays a major role in germination, seedling growth and seed treatment by pesticides. An experimental set-up was designed for investigating the mechanisms of seed coat permeation, which allows steady-state experiments with isolated seed coats of Pisum sativum. Permeances were measured for a set of organic model compounds with different physicochemical properties and sizes. The results show that narrow aqueous pathways dominate the diffusion of solutes across pea seed coats, as indicated by a correlation of permeances with the molecular sizes of the compounds instead of their lipophilicity. Further indicators for an aqueous pathway are small size selectivity and a small effect of temperature on permeation. The application of an osmotic water potential gradient across isolated seed coats leads to an increase in solute transfer, indicating that the aqueous pathways form a water-filled continuum across the seed coat allowing the bulk flow of water. Thus, the uptake of organic solutes across pea testae has two components: (1) by diffusion and (2) by bulk water inflow, which, however, is relevant only during imbibition.

The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells.

Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global loss of methylation takes place during PGC expansion and migration with evidence for passive demethylation, but sequences that carry long-term epigenetic memory (imprints, CpG islands on the X chromosome, germline-specific genes) only become demethylated upon entry of PGCs into the gonads. The transcriptional profile of PGCs is tightly controlled despite global hypomethylation, with transient expression of the pluripotency network, suggesting that reprogramming and pluripotency are inextricably linked. Our results provide a framework for the understanding of the epigenetic ground state of pluripotency in the germline.

Gains of item-specific training in visual working memory and their neural correlates.

Experts sometimes show higher working memory performance than novices but contrary to this finding, evidence for a positive effect of item-specific training is rare. This study provides evidence for item-specific training gains. We presented Chinese characters and artificial patterns (spotted figures) in a change detection task before and after training (varying set size from 1 to 3). A part of the Chinese characters were trained; others and the spotted figures were not trained. Memory capacity was between one and two items. For set size two, memory performance for trained characters was higher than for untrained characters and they were processed faster. Within superior intraparietal sulcus and middle occipital cortex (part of the putative posterior working memory network), the neural activity asymptotically increased with set size. Untrained items reached the activation maximum already at set size two. For this set size, the activity was significantly reduced for trained items so that a further increase from two to three items was observed. We interpret this difference as a correlate of a gain in neural efficiency. The size of this difference correlated with the training gain in memory. We assume that training causes a more efficient neural representation of trained items supported by long-term memory and this allows holding more items in working memory.

HBsAg blood screening and diagnosis: performance evaluation of the ARCHITECT HBsAg qualitative and ARCHITECT HBsAg qualitative confirmatory assays.

A low initial reactive rate for screening assays is important for time- and cost-effective infectious disease testing. Therefore, the new ARCHITECT HBsAg Qualitative screening assay, in conjunction with the new ARCHITECT HBsAg Qualitative Confirmatory assay, was introduced. As the role of hepatitis B surface antigen (HBsAg) as surrogate marker for HBV resolution and the monitoring of drug effectiveness are becoming increasingly important, the established ARCHITECT HBsAg Quantitative assay remains available on the market. Precision, sensitivity, and specificity of the newly developed screening assay were in the range of established HBsAg assays. Seroconversion sensitivity was slightly superior compared to other commercially available assays. An initial reactive rate of 0.2% (without HBsAg-confirmed positive samples of 0.17%) for the ARCHITECT HBsAg Qualitative assay was observed. As the new screening assay is a 1-step assay format, the "high-dose hook effect" was investigated to assess the risk of false-negative results, but even very high positive HBsAg samples obtained signals clearly above the cutoff.

Polycomb purification by in vivo biotinylation tagging reveals cohesin and Trithorax group proteins as interaction partners.

The maintenance of specific gene expression patterns during cellular proliferation is crucial for the identity of every cell type and the development of tissues in multicellular organisms. Such a cellular memory function is conveyed by the complex interplay of the Polycomb and Trithorax groups of proteins (PcG/TrxG). These proteins exert their function at the level of chromatin by establishing and maintaining repressed (PcG) and active (TrxG) chromatin domains. Past studies indicated that a core PcG protein complex is potentially associated with cell type or even cell stage-specific sets of accessory proteins. In order to better understand the dynamic aspects underlying PcG composition and function we have established an inducible version of the biotinylation tagging approach to purify Polycomb and associated factors from Drosophila embryos. This system enabled fast and efficient isolation of Polycomb containing complexes under near physiological conditions, thereby preserving substoichiometric interactions. Novel interacting proteins were identified by highly sensitive mass spectrometric analysis. We found many TrxG related proteins, suggesting a previously unrecognized extent of molecular interaction of the two counteracting chromatin regulatory protein groups. Furthermore, our analysis revealed an association of PcG protein complexes with the cohesin complex and showed that Polycomb-dependent silencing of a transgenic reporter depends on cohesin function.

Retrotransposons and germ cells: reproduction, death, and diversity.

The evolutionary success of retrotransposable elements is reflected by their abundance in mammalian genomes. To restrict their further advance, a number of defence mechanisms have been put in place by the host. These seem to be particularly effective in the germ line while somatic lineages might be more permissive to new insertions, as recent work by Kano and colleagues suggests.

Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency.

Epigenetic reprogramming including demethylation of DNA occurs in mammalian primordial germ cells (PGCs) and in early embryos, and is important for the erasure of imprints and epimutations, and the return to pluripotency. The extent of this reprogramming and its molecular mechanisms are poorly understood. We previously showed that the cytidine deaminases AID and APOBEC1 can deaminate 5-methylcytosine in vitro and in Escherichia coli, and in the mouse are expressed in tissues in which demethylation occurs. Here we profiled DNA methylation throughout the genome by unbiased bisulphite next generation sequencing in wild-type and AID-deficient mouse PGCs at embryonic day (E)13.5. Wild-type PGCs revealed marked genome-wide erasure of methylation to a level below that of methylation deficient (Np95(-/-), also called Uhrf1(-/-)) embryonic stem cells, with female PGCs being less methylated than male ones. By contrast, AID-deficient PGCs were up to three times more methylated than wild-type ones; this substantial difference occurred throughout the genome, with introns, intergenic regions and transposons being relatively more methylated than exons. Relative hypermethylation in AID-deficient PGCs was confirmed by analysis of individual loci in the genome. Our results reveal that erasure of DNA methylation in the germ line is a global process, hence limiting the potential for transgenerational epigenetic inheritance. AID deficiency interferes with genome-wide erasure of DNA methylation patterns, indicating that AID has a critical function in epigenetic reprogramming and potentially in restricting the inheritance of epimutations in mammals.

Characterization of hydrophilic and lipophilic pathways of Hedera helix L. cuticular membranes: permeation of water and uncharged organic compounds.

The permeability of astomatous leaf cuticular membranes of Hedera helix L. was measured for uncharged hydrophilic (octanol/water partition coefficient log K(O/W) < or =0) and lipophilic compounds (log K(O/W) >0). The set of compounds included lipophilic plant protection agents, hydrophilic carbohydrates, and the volatile compounds water and ethanol. Plotting the mobility of the model compounds versus the molar volume resulted in a clear differentiation between a lipophilic and a hydrophilic pathway. The size selectivity of the lipophilic pathway was described by the free volume theory. The pronounced tortuosity of the diffusional path was caused by cuticular waxes, leading to an increase in permeance for the lipophilic compounds after wax extraction. The size selectivity of the hydrophilic pathway was described by hindered diffusion in narrow pores of molecular dimensions. A distinct increase in size selectivity was observed for hydrophilic compounds with a molar volume higher than 110 cm3 mol(-1). Correspondingly, the size distribution of passable hydrophilic pathways was interpreted as a normal distribution with a mean pore radius of 0.3 nm and a standard deviation of 0.02 nm. The increased permeance of the hydrophilic compounds by the removal of cuticular waxes was attributed to an increase in the porosity, a decrease in the tortuosity, and a widening of the pore size distribution. Cuticular transpiration resulted from the permeation of water across the hydrophilic pathway. The far-reaching implications of two parallel pathways for the establishment of correlations between cuticular structure, chemistry, and function are discussed.