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The objective of our study was to evaluate a single blood collection tube with a novel antithrombotic formulation to measure both hematological, biochemical, and d-dimer analytes.Paired samples of gold standard blood tubes (EDTA, lithium heparin, sodium citrate) and a new antithrombotic formulation blood tube were collected from 187 patients. The new antithrombotic tube is a lithium heparin tube preloaded with a liquid form of prostacyclin analog. The novel tube was tested on seventeen hematological parameters and smears against EDTA, on fourteen biochemical parameters against lithium heparin and on d-dimer against sodium citrate.All correlation coefficients were close to 0.99. The Bland-Altman analyses presented a satisfactory correspondence for all analytes. All the hematological examinations demonstrated comparable results between EDTA and the novel formulation, except for platelet counts analyzed by impedance method, but not by fluorescence. We detected lower mean platelet volume with/without outliers (5.06%)/(5.13%) in the novel formulation and increased mean corpuscular hemoglobin concentration (2.55%). All the biochemistry analytes demonstrated comparable results between lithium heparin and the novel tube. d-dimer showed comparable results between citrated blood and the novel formulation after dilution correction.We describe a novel antithrombotic formulation tube with the potential to be introduced into clinical laboratories for simultaneous analysis of thirty-two blood analytes.

Among the applications, glyphosate-based herbicides are used for pre-harvest crop desiccation and weed management in glyphosate resistant crops. Due to these applications glyphosate residues have been found in feedstuff for conventional livestock. Besides its herbicidal property, glyphosate has documented mineral chelating and antimicrobial properties. Previous studies have found glyphosate residuals in animal organs, and glyphosate may cause adverse effects in animals during the embryonic or neonatal period. The present study has two endpoints; a) whether glyphosate concentration in the diets fed to sows during early gestation, was associated with the frequency of congenital tail kinks and stillborn piglets, and b) whether the glyphosate concentration in diets fed to lactating sows, is associated with the frequency of diarrhoea in neonatal piglets. The concentration of glyphosate in 78 gestation diets obtained from seven Danish conventional sow herds ranged from 0.08 to 1.52 mg/kg dry matter (DM) and in 34 lactation diets from 0.06 to 0.87 mg/kg DM. When correcting for an average DM content of 88.3% in gestation diets and 89.0% in lactation diets the concentration of glyphosate ranged from 0.07 to 1.34 and 0.05 to 0.77 mg/kg feed, respectively. In the first study, 28,336 docked tails from 2 to 4-day-old piglets were assessed for congenital tail kinks and the number of kinky tails per herd per week was linked to the glyphosate concentration in sow diets during week 1 to 6 of gestation. Percentage of kinky tails and stillborn piglets ranged from 0 to 2.60% and 0.7 to 3.2% per week, respectively. No associations between the glyphosate concentration in sow gestation diets and the frequency of kinky tails or stillborn piglets were found. In the second study, faeces consistency of 5,526 piglets from 386 litters was linked to the glyphosate concentration in sow lactation diets. A proportion of 0.15 of the 0- to 5-day-old piglets had diarrhoea. No association was found between the concentration of glyphosate in sow lactation diets and the frequency of diarrhoea in neonatal piglets.

Farm management systems and seasonal variation are suggested to affect the concentrations of phytoestrogens in milk. The present study analyses the concentrations of phytoestrogens and their relative composition in distinct milk lines from six Danish dairies representing three management systems (conventional, organic and biodynamic) in five sampling periods (P1–P5) over one year. A highly selective and sensitive liquid chromatography-triple quadrupole mass spectrometry method was applied to determine absolute concentrations of phytoestrogens in the different milk lines over the period. Biodynamic dairy milk lines contained higher levels of most isoflavones compared with milk from conventional systems. This may be explained by the differences in feeding strategies and, more specifically, botanical composition of feed. In relation to season, the concentration of the mammalian derived isoflavone, equol, was highest during the indoor period in biodynamic milk. Compared with the isoflavones, concentrations of lignans were less affected by farm management system.

Here, we present a protocol for assessing metabolic activity of bacterial populations by measuring heat flow using isothermal calorimetry. We outline the steps for preparing the different growth models of Pseudomonas aeruginosa and performing continuous metabolic activity measurements in the calScreener. We detail simple principal component analysis to differentiate between metabolic states of different populations and probabilistic logistic classification to assess resemblance to wild-type bacteria. This protocol for fine-scale metabolic measurement can aid in understanding microbial physiology. For complete details on the use and execution of this protocol, please refer to Lichtenberg et al. (2022).1

Following open-heart surgery, atrial fibrillation and stroke occur frequently. Left atrial appendage closure added to elective open-heart surgery could reduce the risk of ischemic stroke. We aim to examine if routine closure of the left atrial appendage in patients undergoing open-heart surgery provides long-term protection against cerebrovascular events independently of atrial fibrillation history, stroke risk, and oral anticoagulation use. Long-term follow-up of patients enrolled in the prospective, randomized, open-label, blinded evaluation trial entitled left atrial appendage closure by surgery (NCT02378116). Patients were stratified by oral anticoagulation status and randomized (1:1) to left atrial appendage closure in addition to elective open-heart surgery vs standard care. The primary composite endpoint was ischemic stroke events, transient ischemic attacks, and imaging findings of silent cerebral ischemic lesions. Two neurologists blinded for treatment assignment adjudicated cerebrovascular events. In total, 186 patients (82% males) were reviewed. At baseline, mean (standard deviation (SD)) age was 68 (9) years and 13.4% (n = 25/186) had been diagnosed with atrial fibrillation. Median [interquartile range (IQR)] CHA

Contains fulltext : 220386.pdf (Publisher’s version ) (Open Access) Loss of expression of the transcription regulator DC-SCRIPT (Zfp366) is a prominent prognostic event in estrogen receptor-positive breast cancer patients. Studying the inherent link between breast morphogenesis and tumorigenesis, we recently reported that DC-SCRIPT affects normal mammary branching morphogenesis and mammary epithelium homeostasis. Here we investigated the molecular mechanism involved in DC-SCRIPT mediated regulation of FGF2 induced mammary branching morphogenesis in a 3D organoid culture system. Our data show that the delayed mammary organoid branching observed in DC-SCRIPT(-/-) organoids cannot be compensated for by increasing FGF2 levels. Interestingly, FGFR1, the dominant FGF2 receptor, was expressed at a significantly lower level in basal epithelial cells of DC-SCRIPT deficient organoids relative to wildtype organoids. A potential link between DC-SCRIPT and FGFR1 was further supported by the predicted locations of the DC-SCRIPT DNA binding motif at the Fgfr1 gene. Moreover, ERK1/2 phosphorylation downstream of the FGFR1 pathway was decreased in basal epithelial cells of DC-SCRIPT deficient organoids. Altogether, this study shows a relationship between DC-SCRIPT and FGFR1 related pERK signaling in modulating the branching morphogenesis of mammary organoids in vitro.

Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low-passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.

Background: Pseudomonas aeruginosa is a major pathogen of the chronic lung infections in cystic fibrosis (CF) patients. These persistent bacterial infections are characterized by bacterial aggregates with biofilm-like properties and are treated with nebulized or intravenous tobramycin in combination with other antibiotics. However, the chronic infections are close to impossible to eradicate due to reasons that are far from fully understood. Recent work has shown that re‑oxygenation of hypoxic aggregates by hyperbaric oxygen (O2) treatment (HBOT: 100% O2 at 2.8 bar) will increase killing of aggregating bacteria by antibiotics. This is relevant for treatment of infected CF patients where bacterial aggregates are found in the endobronchial secretions that are depleted of O2 by the metabolism of polymorphonuclear leukocytes (PMNs). The main objective of this study was to investigate the effect of HBOT as an adjuvant to tobramycin treatment of aggregates formed by P. aeruginosa isolates from CF patients. Methods: The effect was tested using a model with bacterial aggregates embedded in agarose. O2 profiling was used to confirm re‑oxygenation of aggregates. Results: We found that HBOT was able to significantly enhance the effect of tobramycin against aggregates of all the P. aeruginosa isolates in vitro. The effect was attributed to increased O2 levels leading to increased growth and thus increased uptake of and killing by tobramycin. Conclusions: Re‑oxygenation may in the future be a clinical possibility as adjuvant to enhance killing by antibiotics in cystic fibrosis lung infections.

Identifying and understanding relationships between the electronic and atomic structure of surfaces and their catalytic activity is an essential step towards the rational design of heterogeneous catalysts for both thermal and electrochemical applications. Herein, we identify a relationship between the atom-projected density of states of surface oxygen and its ability to make and break bonds with the surrounding metal atoms and hydrogen. This structure-property relationship is shown to hold across different classes of materials (metals, rutile metal-oxides, and perovskite metal-oxides) and for different oxygen binding sites (i.e. different oxygen coordination numbers). We utilize understanding from the d-band model and the simple two-level quantum coupling problem to shed light on the physical origin of this relationship for transition metal surfaces and we hypothesize similar principles extend to the other materials considered. Finally, we demonstrate the utility of the identified descriptor to serve as a tool for high throughput screening of oxygen active sites for large systems where many unique oxygen sites exist and can be computationally expensive to probe individually. As an example, we predict the reactivity of 36 unique oxygen atoms at a kinked RuO2 extended surface from a single self-consistent DFT calculation.

Bacteria in biofilms are embedded in extracellular matrix and display low metabolic activity, partly due to insufficient diffusive exchange of metabolic substrate. The extracellular matrix and low metabolic activity both contribute to the high antibiotic tolerance-the hallmark of biofilm bacteria. The second messenger molecule, c-di-GMP, regulates biofilm development in Pseudomonas aeruginosa, where high internal levels lead to biofilm formation and low levels are associated with planktonic bacteria. Using a microcalorimetric approach, we show that c-di-GMP signaling is a major determinant of the metabolic activity of P. aeruginosa, both in planktonic culture and in two biofilm models. The high c-di-GMP content of biofilm bacteria forces them to rapidly spend a large amount of energy on the production of exopolysaccharides, resulting in a subsequent low metabolic state. This suggests that the low metabolic state of bacteria in mature biofilms, to some extent, is a consequence of a c-di-GMP-regulated survival strategy.

This research examines the perceived fairness of two types of job interviews: robot-mediated and face-to-face interviews. The robot-mediated interview tests the concept of a fair proxy in the shape of a teleoperated social robot. In Study 1, a mini-public (n=53) revealed four factors that influence fairness perceptions of the robot-mediated interview and showed how HR professionals’ perception of fair personnel selection is influenced by moral pragmatism despite clear moral awareness of discriminative biases in interviews. In Study 2, an experimental survey (n=242) conducted at an unemployment center showed that the respondents perceived the robot-mediated interview as fairer than the face-to-face interview. Overall, the studies suggest that HR professionals and jobseekers exhibit diverging fairness perceptions and that the business case for the robot-mediated interview undermines its social case (i.e., reducing discrimination). The paper concludes by addressing key implications and avenues for future research.

Understanding groundwater abstraction effects is vital for holistic impact assessments in areas depending on groundwater resources. The objective of our study was to modify the state-of-the-art AWaRe (available water remaining), freshwater impact assessment specifically for use in LCAs in areas dependent on groundwater resources. The new method, called “AGWaRe” (available groundwater remaining), reflects groundwater availability, based on a fraction of available groundwater remaining locally relative to a reference. Furthermore, our method increases spatial resolution beyond 1770 km2 grid cells and adjusts demarcations in order to improve the representation of the heterogeneity of groundwater catchments. The applicability of AGWaRe was demonstrated on three groundwater systems producing 5 million m3 water for the city of Copenhagen, namely Advanced Treatment of Groundwater, Simple Treatment of Groundwater and Infiltration of Reclaimed water. Results were normalised to compare with other effects of supplying water to an average Danish person. The normalised impacts for drinking water for one person ranged between 0.1 and 39 PE (person equivalent) for the three systems, which indicates that effects on groundwater resources differ substantially between systems. A comparative LCA of these groundwater systems shows that other impact categories range between 0 and 1 PE/person. Advanced Treatment of Groundwater generally has the lowest effect, for example