'EUROPART'. Airborne particles in the indoor environment. A European interdisciplinary review of scientific evidence on associations between exposure to particles in buildings and health effects

The relevance of particle mass, surface area or number concentration as risk indicators for health effects in non-industrial buildings has been assessed by a European interdisciplinary group of researchers (called EUROPART) by reviewing papers identified in Medline, Toxline, and OSH. Studies dealing with dermal effects or cancer or specifically addressing environmental tobacco smoke, house dust-mite, cockroach or animal allergens, microorganisms and pesticides were excluded. A total of 70 papers were reviewed, and eight were identified for the final review: Five experimental studies involving mainly healthy subjects, two cross-sectional office studies and one longitudinal study among elderly on cardiovascular effects. From most studies, no definite conclusions could be drawn. Overall, the group concluded that there is inadequate scientific evidence that airborne, indoor particulate mass or number concentrations can be used as generally applicable risk indicators of health effects in non-industrial buildings and consequently that there is inadequate scientific evidence for establishing limit values or guidelines for particulate mass or number concentrations.     

Distribution of selected anthropogenic radionuclides (137Cs, 238Pu, (239,240)Pu and 241Am) in marine sediments with emphasis on the Spitsbergen-Bear Island area

Measurements of anthropogenic radionuclides in marine sediments can provide good estimates of past and present radioactive contamination of the marine environment. The Barents Sea is one of the world's richest ocean areas, and it is therefore of major interest for Norwegian fisheries to document the levels of radioactive contamination of this and adjacent ocean areas. In this study, concentrations of 137Cs, 238Pu, (239,240)Pu and 241Am were measured in marine sediments collected mainly in the Spitsbergen-Bear Island region. Additional samples collected in the deep Norwegian Sea and near the Greenland ice-edge have been included for comparison. The highest radionuclide levels were found near Spitsbergen, reaching over 50% higher than in adjacent areas. Determinations of the mineral content and particle size distribution indicate a relation between the content of clay minerals and radionuclide levels. The present study confirms earlier observations of elevated levels of 137Cs in sediments in the Spitsbergen-Bear Island area and documents elevated levels of 238Pu, (239,240)Pu and 241Am in these sediments. Using an exponential curve fit based on determinations of unsupported 210Pb in sediment cores, sedimentation rates of 0.28, 0.05 and 0.26 cm year(-1) were calculated at locations south of Spitsbergen, near the Greenland ice-edge and in the deep Norwegian Sea, respectively.     

Sorption of phosphorous to Filtralite-P--the effect of different scales

Sorption of P to the filter material Filtralite-P was examined at a small, medium and large scale. In the small- and meso-scale laboratory models, the sorbed amount of total phosphorus (P) was heterogeneously distributed with more P sorbed in the inlet zone and the bottom layers. The full-scale system had, on the other hand, the highest sorbed concentration in the outlet region. The overall P sorption capacity of the material was 8030, 4990 and 521 mg P kg(-1) Filtralite-P for Box 1, Box 2 and meso scale, respectively. This equals 4.4, 2.8 and 0.29 kg P m(-3) material, respectively. However, the maximum sorption capacities found were 2500, 3887 and 4500 mg P kg(-1) Filtralite-P for the two small-scale box systems and the meso-scale container, respectively. In the full-scale system the overall P sorption capacity of the material was 52 mg P kg(-1) Filtralite-P (0.029 kg P m(-3) Filtralite-P with a maximum sorbed amount of P of 249 mg P kg(-1). Results from both the small- and meso-scale system show that when a constructed wetland (CW) is saturated, i.e. when the outlet concentration has reached its maximum allowed concentration of 1.0 mg P l(-1), only parts of the filter material will have reached the sorption capacity. Sequential extractions of Filtralite-P showed that the loosely bound P, Ca-P and Al-P were the primary P sorption pools both in the small-scale models and in the full-scale CW. However, the proportion of these three fractions varied with time and change in pH. A white product precipitated in the outlet zone of both the small-scale box models as well as the onsite CW. The surface of these precipitation particles was identified by X-ray diffraction and SEM method as CaCO3 and precipitated Ca- and Mg-phosphates.     

The SARS-CoV-2 Delta-Omicron Recombinant Lineage (XD) Exhibits Immune-Escape Properties Similar to the Omicron (BA.1) Variant

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.     

Robust Classification Using Posterior Probability Threshold Computation Followed by Voronoi Cell Based Class Assignment Circumventing Pitfalls of Bayesian Analysis of Biomedical Data

Bayesian inference is ubiquitous in science and widely used in biomedical research such as cell sorting or “omics” approaches, as well as in machine learning (ML), artificial neural networks, and “big data” applications. However, the calculation is not robust in regions of low evidence. In cases where one group has a lower mean but a higher variance than another group, new cases with larger values are implausibly assigned to the group with typically smaller values. An approach for a robust extension of Bayesian inference is proposed that proceeds in two main steps starting from the Bayesian posterior probabilities. First, cases with low evidence are labeled as “uncertain” class membership. The boundary for low probabilities of class assignment (threshold ε) is calculated using a computed ABC analysis as a data-based technique for item categorization. This leaves a number of cases with uncertain classification (p < ε). Second, cases with uncertain class membership are relabeled based on the distance to neighboring classified cases based on Voronoi cells. The approach is demonstrated on biomedical data typically analyzed with Bayesian statistics, such as flow cytometric data sets or biomarkers used in medical diagnostics, where it increased the class assignment accuracy by 1–10% depending on the data set. The proposed extension of the Bayesian inference of class membership can be used to obtain robust and plausible class assignments even for data at the extremes of the distribution and/or for which evidence is weak.     

Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin

The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber–film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.     

A digital system for surface roughness analysis of plane and cylindrical parts

This paper describes an on-line system for digital analysis of surfaces where the electrical signal from a surface roughness instrument is converted and input into a desk-top computer which also controls the traversing. Special fixtures integrated with the system and dedicated software permit two- and three-dimensional tracings to be carried out on plane as well as on cylindrical parts. The surface profiles can be plotted in different ways. Roughness parameters, frequency spectra etc, can be computed digitally and all results can be stored. Scratches and irregularities on the surface can be identified and processed separately from the rest of the surface. The desk-top computer is connected to the university mainframe computer through a modem, this being of advantage in connection with graphic data processing. The capability of the equipment has been investigated and results from calibration are presented.     

Liquefaction,Saccharification and Isomerization of Starches from Sources Other than Maize

Examination of the suitability of a number of starches for the production of fructose syrup is described. In addition to maize starch, starch from wheat, potatoes and tapioca has been examined. Liquefaction, saccharification and purification were performed in pilot scale, whereas the produced syrups were isomerized in laboratory scale. The liquefactions were performed with Termamyl® in a jet cooker process. Saccharification with Amyloglucosidase Novo 150 L under standard conditions gave good DX values. After purification the syrups were isomerized in laboratory columns with Sweetzyme®. The results - activity and productivity of Sweetzyme - were for all syrups as good as or better than those obtained with dextrose solutions.     

Perinatal Obesity Induces Hepatic Growth Restriction with Increased DNA Damage Response,Senescence, and Dysregulated Igf-1-Akt-Foxo1 Signaling in Male Offspring of Obese Mice

Maternal obesity predisposes for hepato-metabolic disorders early in life. However, the underlying mechanisms causing early onset dysfunction of the liver and metabolism remain elusive. Since obesity is associated with subacute chronic inflammation and accelerated aging, we test the hypothesis whether maternal obesity induces aging processes in the developing liver and determines thereby hepatic growth. To this end, maternal obesity was induced with high-fat diet (HFD) in C57BL/6N mice and male offspring were studied at the end of the lactation [postnatal day 21 (P21)]. Maternal obesity induced an obese body composition with metabolic inflammation and a marked hepatic growth restriction in the male offspring at P21. Proteomic and molecular analyses revealed three interrelated mechanisms that might account for the impaired hepatic growth pattern, indicating prematurely induced aging processes: (1) Increased DNA damage response (γH2AX), (2) significant upregulation of hepatocellular senescence markers (Cdnk1a, Cdkn2a); and (3) inhibition of hepatic insulin/insulin-like growth factor (IGF)-1-AKT-p38-FoxO1 signaling with an insufficient proliferative growth response. In conclusion, our murine data demonstrate that perinatal obesity induces an obese body composition in male offspring with hepatic growth restriction through a possible premature hepatic aging that is indicated by a pathologic sequence of inflammation, DNA damage, senescence, and signs of a possibly insufficient regenerative capacity.     

The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.