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•Mixture effects of neurotoxicants demonstrated to be relevant for human health.•30,000 suspected neurotoxicants were screened for likelihood of human exposure.•58 chemicals predicted ...to occur in blood may contribute to mixture neurotoxicity.•Data gaps in in vitro neurotoxicity were closed with baseline toxicity predictions.•Generalized workflow applicable to chemical mixtures with other modes of action.
Modern society continues to pollute the environment with larger quantities of chemicals that have also become more structurally and functionally diverse. Risk assessment of chemicals can hardly keep up with the sheer numbers that lead to complex mixtures of increasing chemical diversity including new chemicals, substitution products on top of still abundant legacy compounds. Fortunately, over the last years computational tools have helped us to identify and prioritize chemicals of concern. These include toxicokinetic models to predict exposure to chemicals as well as new approach methodologies such as in-vitro bioassays to address toxicodynamic effects. Combined, they allow for a prediction of mixtures and their respective effects and help overcome the lack of data we face for many chemicals. In this study we propose a high-throughput approach using experimental and predicted exposure, toxicokinetic and toxicodynamic data to simulate mixtures, to which a virtual population is exposed to and predict their mixture effects. The general workflow is adaptable for any type of toxicity, but we demonstrated its applicability with a case study on neurotoxicity. If no experimental data for neurotoxicity were available, we used baseline toxicity predictions as a surrogate. Baseline toxicity is the minimal toxicity any chemical has and might underestimate the true contribution to the mixture effect but many neurotoxicants are not by orders of magnitude more potent than baseline toxicity. Therefore, including baseline-toxic effects in mixture simulations yields a more realistic picture than excluding them in mixture simulations. This workflow did not only correctly identify and prioritize known chemicals of concern like benzothiazoles, organochlorine pesticides and plasticizers but we were also able to identify new potential neurotoxicants that we recommend to include in future biomonitoring studies and if found in humans, to also include in neurotoxicity screening.
Springtail skin morphology is translated into robust omniphobic polymer membranes by reverse imprint lithography. The combination of overhanging cross‐sections and their arrangement in a ...self‐supporting comblike pattern are crucial for mechanically stable coatings that can be even applied to curved surfaces.
Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. However, the clinical significance remains ...poorly defined. We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment.
Respiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR. ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 10
HSV copies/mL) and low (10
-10
HSV copies/mL) viral load.
Fifty-seven low and 69 high viral load patients were identified. Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001). Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11-0.92, p = 0.035) in high load patients only. Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 μg/kg body weight/min between days 0 and 6 of treatment (p = 0.049), and median PaO
/FiO
ratio increased from 187 to 241 between day 3 and day 7 of treatment (p = 0.02). Chest radiographic findings also improved significantly (p < 0.001).
In patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function. This suggests a causative role for HSV in this highly selected group of patients.
Background COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of ...the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. Methods During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. Results Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. Conclusions The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patterned Polypeptoid Brushes Schneider, Maximilian; Tang, Zian; Richter, Marcus ...
Macromolecular bioscience,
January 2016, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Patterned polypeptoid brushes on gold and oxide substrates are synthesized by surface‐initiated polymerization of N‐substituted glycine N‐carboxyanhydrides. Their biofouling resistance is shown by ...protein and cell adhesion experiments. The accessibility of the system to common patterning protocols is demonstrated by UV‐lithography and a μCP approach. Moreover, the terminal secondary amine group of the polypeptoid brushes is functionalized with different fluorescent dyes to demonstrate their chemical accessibility.
The preparation of patterned polypeptoid (POI) brushes on gold and oxide substrates by surface‐initiated polymerization of N‐substituted glycine N‐carboxyanhydrides from patterned self‐assembled monolayers is presented. Furthermore, the chemoselective functionalization and anti‐biofouling properties of POI brushes are shown.
We study supercritical branching processes under the influence of an independent and identically distributed (i.i.d.) emigration component. We provide conditions under which the lifetime of the ...process is finite or has a finite expectation. A theorem of Kesten–Stigum type is obtained, and the extinction probability for a large initial population size is related to the tail behaviour of the emigration.
Zusammenfassung
Hintergrund
Das Vorliegen einer gastrointestinalen Dysfunktion ist eine outcomerelevante Komplikation des kritisch kranken Patienten auf der ICU.
Ziel der Arbeit, Material und ...Methoden
Die folgende Übersichtsarbeit soll die Bedeutung einer gastrointestinalen Dysfunktion aufzeigen. Die multimodale Therapie einer Magenentleerungsstörung und eines paralytischen Ileus wird erörtert.
Ergebnisse
Erythromycin und Metoclopramid sind medikamentöse Therapieoptionen bei Magenentleerungsstörung, Neostigmin bei paralytischem Ileus.
The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients.
The following review aims to show the importance of gastrointestinal dysfunction. ...Multimodal therapy for gastroparesis and paralytic ileus is discussed.
Erythromycin and metoclopramide are options for gastroparesis, while neostigmine is commonly used for paralytic ileus.
The direct contact of ultrathin polymer films with a solid substrate may result in thin film rupture caused by dewetting. With crystallisable polymers such as polyethyleneoxide (PEO), molecular ...self-assembly into partial ordered lamella structures is studied as an additional source of pattern formation. Morphological features in ultrathin PEO films (thickness < 10 nm) result from an interplay between dewetting patterns and diffusion limited growth pattern of ordered lamella growing within the dewetting areas. Besides structure formation of hydrophilic PEO molecules, n-alkylterminated (hydrophobic) PEO oligomers are investigated with respect to self-organization in ultrathin films. Morphological features characteristic for pure PEO are not changed by the presence of the n-alkylgroups.
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