Oxidation of pharmaceuticals during water treatment with chlorine dioxide

The potential of chlorine dioxide (ClO2) for the oxidation of pharmaceuticals during water treatment was assessed by determining second-order rate constants for the reaction with selected environmentally relevant pharmaceuticals. Out of 9 pharmaceuticals only the 4 following compounds showed an appreciable reactivity with ClO2 (in brackets apparent second-order rate constants at pH 7 and T = 20 degrees C): the sulfonamide antibiotic sulfamethoxazole (6.7 x 10(3) M(-1) s(-1)), the macrolide antibiotic roxithromycin (2.2 x 10(2) M(-1) s(-1)), the estrogen 17alpha-ethinylestradiol (approximately 2 x 10(5) M(-1) s(-1)), and the antiphlogistic diclofenac (1.05 x 10(4) M(-1) s(-1)). Experiments performed using natural water showed that ClO2 also reacted fast with other sulfonamides and macrolides, the natural hormones estrone and 17beta-estradiol as well as 3 pyrazolone derivatives (phenazone, propylphenazone, and dimethylaminophenazone). However, many compounds in the study were ClO2 refractive. Experiments with lake water and groundwater that were partly performed at microgram/L to nanogram/L levels proved that the rate constants determined in pure water could be applied to predict the oxidation of pharmaceuticals in natural waters. Compared to ozone, ClO2 reacted more slowly and with fewer compounds. However, it reacted faster with the investigated compounds than chlorine. Overall, the results indicate that ClO2 will only be effective to oxidize certain compound classes such as the investigated classes of sulfonamide and macrolide antibiotics, and estrogens.     

Comparison of satellite reflectance algorithms for estimating turbidity and cyanobacterial concentrations in productive freshwaters using hyperspectral aircraft imagery and dense coincident surface observations

We analyzed 37 satellite reflectance algorithms and 321 variants for five satellites for estimating turbidity in a freshwater inland lake in Ohio using coincident real hyperspectral aircraft imagery converted to relative reflectance and dense coincident surface observations. This study is part of an effort to develop simple proxies for turbidity and algal blooms and to evaluate their performance and portability between satellite imagers for regional operational turbidity and algal bloom monitoring. Turbidity algorithms were then applied to synthetic satellite images and compared to in situ measurements of turbidity, chlorophyll-a (Chl-a), total suspended solids (TSS) and phycocyanin as an indicator of cyanobacterial/blue green algal (BGA) abundance. Several turbidity algorithms worked well with real Compact Airborne Spectrographic Imager (CASI) and synthetic WorldView-2, Sentinel-2 and Sentinel-3/MERIS/OLCI imagery. A simple red band algorithm for MODIS imagery and a new fluorescence line height algorithm for Landsat-8 imagery had limited performance with regard to turbidity estimation. Blue-Green Algae/Phycocyanin (BGA/PC) and Chl-a algorithms were the most widely applicable algorithms for turbidity estimation because strong co-variance of turbidity, TSS, Chl-a, and BGA made them mutual proxies in this experiment.     

Integrated Devices for Non-Invasive Diagnostics

“Sample-in-answer-out” type integrated diagnostic devices have been widely recognized as the ultimate solution to simplify testing across healthcare systems. Such systems are equipped with advanced fluidic, mechanical, chemical, biological, and electronic components to handle patient samples without any manual steps therefore have the potential to accelerate intervention and improve patient outcomes. In this regard, the combination of integrated devices and non-invasive sampling has gained a substantial interest to further improve the comfort and safety of patients. In this Review, the pioneering developments in integrated diagnostics are covered and their potential in non-invasive sampling is discussed. The key properties of possible sample types are highlighted by addressing their relevance for the clinical practice. Last, the factors affecting the transition of integrated devices from academia to the market are identified by analyzing the technology readiness levels of selected examples and alternative remedies are explored to increase the rate of survival during this transition.     

Soluble polyelectrolyte complexes composed of poly(ethylene oxide)-block-poly(sodium methacrylate) and poly(methacryloyloxyethyl trimethylammonium chloride)

Complexation between poly(methacryloyloxyethyl trimethylammonium chloride), PMOTAC, and poly(ethylene oxide)-block-poly(sodium methacrylate), PEO-block-PMANa with MANa blocks with two different molecular weights has been investigated by light scattering, LS, viscosimetry and conductivity measurements. Owing to the PEO blocks the polyelectrolyte complexes are water-soluble particles. Effects of the ratio of the oppositely charged monomer units, the ionic strength of the solution, and solution pH have been studied. With the 1:1 mixing ratio stable polyelectrolyte complexes, PECs, with spherical shape were formed. When either the cationic or anionic component was in excess, charged non-stoichiometric complexes were formed. The complexes were stable also in solutions with comparatively high ionic strength, though stronger secondary aggregation was observed. By changing the solution pH the degree of dissociation of PEO-block-PMANa could be adjusted. In the vicinity of the pK_a,average of PMAA, a minimum in the particle size and a maximum in the solution conductivity were observed. In solutions with lower pH, a typical self-complexation of PEO-block-PMAA was detected. Also, unexpected interactions between PMOTAC and the self-complexes of PEO-block-PMAA were observed.     

Ezrin Is a Novel Protein Partner of Aquaporin-5 in Human Salivary Glands and Shows Altered Expression and Cellular Localization in Sjögren’s Syndrome

Sjögren’s syndrome (SS) is an exocrinopathy characterized by the hypofunction of salivary glands (SGs). Aquaporin-5 (AQP5); a water channel involved in saliva formation; is aberrantly distributed in SS SG acini and contributes to glandular dysfunction. We aimed to investigate the role of ezrin in AQP5 mislocalization in SS SGs. The AQP5–ezrin interaction was assessed by immunoprecipitation and proteome analysis and by proximity ligation assay in immortalized human SG cells. We demonstrated, for the first time, an interaction between ezrin and AQP5. A model of the complex was derived by computer modeling and in silico docking; suggesting that AQP5 interacts with the ezrin FERM-domain via its C-terminus. The interaction was also investigated in human minor salivary gland (hMSG) acini from SS patients (SICCA-SS); showing that AQP5–ezrin complexes were absent or mislocalized to the basolateral side of SG acini rather than the apical region compared to controls (SICCA-NS). Furthermore, in SICCA-SS hMSG acinar cells, ezrin immunoreactivity was decreased at the acinar apical region and higher at basal or lateral regions, accounting for altered AQP5–ezrin co-localization. Our data reveal that AQP5–ezrin interactions in human SGs could be involved in the regulation of AQP5 trafficking and may contribute to AQP5-altered localization in SS patients     

Graphical displays of human strength data

To facilitate the effective use of strength data in a human-task simulation environment, we have developed graphical methods to display the multidimensional characteristics of strength data. We use human figures together with two and three dimensional graphical symbols, colours and animations to visualize the effects of different parameters on strength. These displays give a dynamic view of the effects of various parameters on strength, and illustrate safe and forbidden body postures (or regions) in terms of strength capabilities.     

Imaging the Kidney with an Unconventional Scanning Electron Microscopy Technique: Analysis of the Subpodocyte Space in Diabetic Mice

Transmission electron microscopy (TEM) remains the gold standard for renal histopathological diagnoses, given its higher resolving power, compared with light microscopy. However, it imposes several limitations on pathologists, including longer sample preparation time and a small observation area. To overcome these, we introduced a scanning electron microscopy (SEM) technique for imaging resin-embedded semi-thin sections of renal tissue. We developed a rapid tissue preparation protocol for experimental models and human biopsies which, alongside SEM digital imaging acquisition of secondary electrons (SE–SEM), enables fast electron microscopy examination, with a resolution similar to that achieved by TEM. We used this unconventional SEM imaging approach to investigate the subpodocyte space (SPS) in BTBR ob/ob mice with type 2 diabetes. Analysis of semi-thin sections with secondary electrons revealed that the SPS had expanded in volume and covered large areas of the glomerular basement membrane, forming wide spaces between the podocyte body and the underlying filtering membrane. Our results show that SE–SEM is a valuable tool for imaging the kidney at the ultrastructural level, filling the magnification gap between light microscopy and TEM, and reveal that in diabetic mice, the SPS is larger than in normal controls, which is associated with podocyte damage and impaired kidney function.     

Extracellular Matrix Synthesis and Remodeling by Mesenchymal Stromal Cells Is Context-Sensitive

Matrix remodeling could be an important mode of action of multipotent mesenchymal stromal cells (MSC) in extracellular matrix (ECM) disease, but knowledge is limited in this respect. As MSC are well-known to adapt their behavior to their environment, we aimed to investigate if their mode of action would change in response to healthy versus pathologically altered ECM. Human MSC-derived ECM was produced under different culture conditions, including standard culture, culture on Matrigel-coated dishes, and stimulation with the pro-fibrotic transforming growth factor-β1 (TGFβ1). The MSC-ECM was decellularized, characterized by histochemistry, and used as MSC culture substrate reflecting different ECM conditions. MSC were cultured on the different ECM substrates or in control conditions for 2 days. Culture on ECM increased the presence of surface molecules with ECM receptor function in the MSC, demonstrating an interaction between MSC and ECM. In MSC cultured on Matrigel-ECM and TGFβ1-ECM, which displayed a fibrosis-like morphology, gene expression of collagens and decorin, as well as total matrix metalloproteinase (MMP) activity in the supernatant were decreased as compared with control conditions. These results demonstrated that MSC adapt to their ECM environment, which may include pathological adaptations that could compromise therapeutic efficacy.     

Repurposing Histaminergic Drugs in Multiple Sclerosis

Multiple sclerosis is an autoimmune disease with a strong neuroinflammatory component that contributes to severe demyelination, neurodegeneration and lesions formation in white and grey matter of the spinal cord and brain. Increasing attention is being paid to the signaling of the biogenic amine histamine in the context of several pathological conditions. In multiple sclerosis, histamine regulates the differentiation of oligodendrocyte precursors, reduces demyelination, and improves the remyelination process. However, the concomitant activation of histamine H1–H4 receptors can sustain either damaging or favorable effects, depending on the specifically activated receptor subtype/s, the timing of receptor engagement, and the central versus peripheral target district. Conventional drug development has failed so far to identify curative drugs for multiple sclerosis, thus causing a severe delay in therapeutic options available to patients. In this perspective, drug repurposing offers an exciting and complementary alternative for rapidly approving some medicines already approved for other indications. In the present work, we have adopted a new network-medicine-based algorithm for drug repurposing called SAveRUNNER, for quantifying the interplay between multiple sclerosis-associated genes and drug targets in the human interactome. We have identified new histamine drug-disease associations and predicted off-label novel use of the histaminergic drugs amodiaquine, rupatadine, and diphenhydramine among others, for multiple sclerosis. Our work suggests that selected histamine-related molecules might get to the root causes of multiple sclerosis and emerge as new potential therapeutic strategies for the disease.