Validation of a Novel Methodology to Evaluate Changes in the Flare Geometry of Renovisceral Bridging Stent-Grafts After Fenestrated Endovascular Aneurysm Repair

Purpose: To validate a novel method to evaluate changes in the geometry of renovisceral bridging stent-grafts (BSGs) in patients undergoing fenestrated endovascular aneurysm repair (fEVAR). Materials and Methods: Retrospective analysis was conducted of serial computed tomography angiograms (CTAs) of 10 fEVAR patients (31 BSGs) with at least 2 years of CTA follow-up. Centerline reconstructions were made through the fenestrated stent-graft (FSG) and each BSG. Flare geometry was reconstructed based on marker coordinates and a mesh of the aortic lumen. The shortest distance was calculated from the top of the flare circumference to the FSG fabric. The amount of flaring was assessed with the flare to fenestration diameter ratio and BSG compression to diameter ratio (D-ratio). All measurements were performed by 2 observers. Interobserver variability was assessed; results are presented as the intraclass correlation coefficient (ICC) and repeatability coefficient (RC). Results: Excellent interobserver agreement was achieved for BSG diameter and flare to fenestration distance calculations (ICC 0.865 and 0.944; RC 2.2% and 4.5%, respectively). Six patients had BSG-related complications during follow-up: 2 type IIIc endoleaks and 4 BSG occlusions. Five of the 6 BSGs with complications showed a considerable change in the D-ratio compared with the first postoperative CTA. Conclusion: Precise assessment of the geometry of visceral BSGs in fEVAR is feasible with the presented method. Geometrical changes that may precede later complications can be detected, which could aid in localization of the origin, but a larger series of patients is necessary to define its true clinical merit

A new perspective on fungal metabolites:Identification of bioactive compounds from fungi using zebrafish embryogenesis as read-out

There is a constant need for new therapeutic compounds. Fungi have proven to be an excellent, but underexplored source for biologically active compounds with therapeutic potential. Here, we combine mycology, embryology and chemistry by testing secondary metabolites from more than 10,000 species of fungi for biological activity using developing zebrafish (Danio rerio) embryos. Zebrafish development is an excellent model for high-throughput screening. Development is rapid, multiple cell types are assessed simultaneously and embryos are available in high numbers. We found that 1,526 fungal strains produced secondary metabolites with biological activity in the zebrafish bioassay. The active compounds from 39 selected fungi were purified by liquid-liquid extraction and preparative HPLC. 34 compounds were identified by a combination of chemical analyses, including LCMS, UV-Vis spectroscopy/ spectrophotometry, high resolution mass spectrometry and NMR. Our results demonstrate that fungi express a wide variety of biologically active compounds, consisting of both known therapeutic compounds as well as relatively unexplored compounds. Understanding their biological activity in zebrafish may provide insight into underlying biological processes as well as mode of action. Together, this information may provide the first step towards lead compound development for therapeutic drug development

Non-covalent synthesis of calix[4]arene-capped porphyrins in polar solvents via ionic interactions

Non-covalent synthesis of calix[4]arene capped porphyrins can be achieved in polar solvents (up to 45% molar fraction of water) via ionic interaction. Thus tetracationic meso-tetrakis(N-alkylpyridinium-3-yl) porphyrins 1a–d and tetra anionic 25,26,27,28-tetrakis(2-ethoxyethoxy)-calix[4]arene tetrasulfonate 2 self-assemble in an entropy driven process in 1:1 stoichiometry with association constants K1·2 as high as 107 M−1 in methanol. The thermodynamic stability remains high even in the presence of competing salts: 10−2 M Bu4NClO4 (4500 times the concentration of the building blocks) gives a reduction in K1·2 of only 10 times. Ternary complexes 1a·2·L using 1-methylimidazole or pyridine as axial ligands (L) have been obtained with L residing outside the assembly cavity

Guest Encapsulation and Self-Assembly of Molecular Capsules in Polar Solvents via Multiple Ionic Interactions

Herein we report the formation and characterization of a novel type of capsules resulting from the self-association between oppositely charged complementary building blocks in MeOH/H2O. The assembly is based on the interaction between tetraamidinium calix[4]arenes 1a-d and tetrasulfonato calix[4]arene 2. Evidence for the formation of the expected 1:1 assemblies is provided by proton NMR, ESI-MS, and ITC. The association process is fast on the NMR time scale and strongly entropy driven, with association constants in the range of 106 M-1. The system 1a·2 shows binding affinity toward acetylcholine, tetramethylammonium, and N-methylquinuclidinium cations

A new perspective on fungal metabolites : identification of bioactive compounds from fungi using zebrafish embryogenesis as read-out

There is a constant need for new therapeutic compounds. Fungi have proven to be an excellent, but underexplored source for biologically active compounds with therapeutic potential. Here, we combine mycology, embryology and chemistry by testing secondary metabolites from more than 10,000 species of fungi for biological activity using developing zebrafish (Danio rerio) embryos. Zebrafish development is an excellent model for high-throughput screening. Development is rapid, multiple cell types are assessed simultaneously and embryos are available in high numbers. We found that 1,526 fungal strains produced secondary metabolites with biological activity in the zebrafish bioassay. The active compounds from 39 selected fungi were purified by liquid-liquid extraction and preparative HPLC. 34 compounds were identified by a combination of chemical analyses, including LCMS, UV-Vis spectroscopy/ spectrophotometry, high resolution mass spectrometry and NMR. Our results demonstrate that fungi express a wide variety of biologically active compounds, consisting of both known therapeutic compounds as well as relatively unexplored compounds. Understanding their biological activity in zebrafish may provide insight into underlying biological processes as well as mode of action. Together, this information may provide the first step towards lead compound development for therapeutic drug development

Coordination Chemistry in Water of a Free and a Lipase-Embedded Cationic NCN-Pincer Platinum Center with Neutral and Ionic Triarylphosphines

The coordination chemistry in aqueous media was studied for the platinum center of low-molecular-weight cationic NCN-pincer platinum complexes [RC₆H₂(CH₂NMe₂)₂-3,5-Pt­(H₂O)-4]⁺ (R = −(CH₂)₃P­(O)­(OEt)­(OC₆H₄NO₂-4) (<b><b>1</b>(OH₂)</b>), H (<b>2­(OH₂)</b>)) as well as of the platinum center of the NCN-pincer platinum cation embedded in the lipase cutinase (<b>cut-1</b>; molecular weight 20 619.3) with various anionic, neutral, and cationic triarylphosphines. A ³¹P NMR study of the coordination of triarylphosphines to the cationic NCN-pincer platinum center in low-molecular-weight <b>[2­(OH₂)]­[OTf]</b> in both D₂O and Tris buffer (Tris = tris­(hydroxylmethyl)­aminomethane) showed that the phosphine–platinum coordination is strongly affected by Tris buffer molecules. Two crystal structures of a NCN-pincer platinum–phosphine and a NCN-pincer platinum–ethanolamine coordination complex with ethanolamine as a functional model of Tris with hydrogen bridges, provoking a dimeric supramolecular structure, confirmed that the coordination observed in solution occurred in the solid state as well. A ³¹P NMR and ESI-MS study of the lipase <b>cut-1</b> showed that the coordination of various triarylphosphines to the enzyme-embedded platinum center is affected by the surrounding protein backbone, discriminating between phosphines on the basis of their size and charge. By using ³¹P NMR spectroscopy and ESI-MS spectrometry, study of the coordination of triarylphosphines to <b>cut-1</b> was possible, thereby avoiding the need for the application of laborious biochemical procedures. To the best of our knowledge, this is the first example of a study involving the selective binding of organic ligands to the metal center of a semisynthetic metalloprotein, unequivocally demonstrating that the well-established coordination chemistry for small-molecule complexes can be transferred to biological molecules. This initial study allows future explorations in the field of selective protein targeting and identification, as in protein profiling or screening studies

Coordination Chemistry in Water of a Free and a Lipase-Embedded Cationic NCN-Pincer Platinum Center with Neutral and Ionic Triarylphosphines

The coordination chemistry in aqueous media was studied for the platinum center of low-molecular-weight cationic NCN-pincer platinum complexes [RC₆H₂(CH₂NMe₂)₂-3,5-Pt­(H₂O)-4]⁺ (R = −(CH₂)₃P­(O)­(OEt)­(OC₆H₄NO₂-4) (<b><b>1</b>(OH₂)</b>), H (<b>2­(OH₂)</b>)) as well as of the platinum center of the NCN-pincer platinum cation embedded in the lipase cutinase (<b>cut-1</b>; molecular weight 20 619.3) with various anionic, neutral, and cationic triarylphosphines. A ³¹P NMR study of the coordination of triarylphosphines to the cationic NCN-pincer platinum center in low-molecular-weight <b>[2­(OH₂)]­[OTf]</b> in both D₂O and Tris buffer (Tris = tris­(hydroxylmethyl)­aminomethane) showed that the phosphine–platinum coordination is strongly affected by Tris buffer molecules. Two crystal structures of a NCN-pincer platinum–phosphine and a NCN-pincer platinum–ethanolamine coordination complex with ethanolamine as a functional model of Tris with hydrogen bridges, provoking a dimeric supramolecular structure, confirmed that the coordination observed in solution occurred in the solid state as well. A ³¹P NMR and ESI-MS study of the lipase <b>cut-1</b> showed that the coordination of various triarylphosphines to the enzyme-embedded platinum center is affected by the surrounding protein backbone, discriminating between phosphines on the basis of their size and charge. By using ³¹P NMR spectroscopy and ESI-MS spectrometry, study of the coordination of triarylphosphines to <b>cut-1</b> was possible, thereby avoiding the need for the application of laborious biochemical procedures. To the best of our knowledge, this is the first example of a study involving the selective binding of organic ligands to the metal center of a semisynthetic metalloprotein, unequivocally demonstrating that the well-established coordination chemistry for small-molecule complexes can be transferred to biological molecules. This initial study allows future explorations in the field of selective protein targeting and identification, as in protein profiling or screening studies

Tracing the animal sources of surface water contamination with Campylobacter jejuni and Campylobacter coli

Campylobacter jejuni and C. coli, the primary agents of human bacterial gastroenteritis worldwide, are widespread in surface water. Several animal sources contribute to surface water contamination with Campylobacter, but their relative contributions thus far remained unclear. Here, the prevalence, genotype diversity, and potential animal sources of C. jejuni and C. coli strains in surface water in the Netherlands were investigated. It was also assessed whether the contribution of the different animal sources varied according to surface water type (i.e. agricultural water, surface water at discharge points of wastewater treatment plants [WWTPs], and official recreational water), season, and local livestock (poultry, pig, ruminant) density. For each surface water type, 30 locations spread over six areas with either high or low density of poultry, ruminants, or pigs, were sampled once every season in 2018-2019. Campylobacter prevalence was highest in agricultural waters (77%), and in autumn and winter (74%), and lowest in recreational waters (46%) and in summer (54%). In total, 76 C. jejuni and 177 C. coli water isolates were whole-genome sequenced. Most C. coli water isolates (78.5%) belonged to hitherto unidentified clones when using the seven-locus sequence type (ST) scheme, while only 11.8% of the C. jejuni isolates had unidentified STs. The origin of these isolates, as defined by core-genome multi-locus sequence typing (cgMLST), was inferred by comparison with Campylobacter strain collections from meat-producing poultry, laying hens, adult cattle, veal calves, small ruminants, pigs, and wild birds. Water isolates were mainly attributed to wild birds (C. jejuni: 60.0%; C. coli: 93.7%) and meat-producing poultry (C. jejuni: 18.9%; C. coli: 5.6%). Wild bird contribution was high among isolates from recreational waters and WWTP discharge points, and in areas with low poultry (C. coli) or high ruminant (C. jejuni) densities. The contribution of meat-producing poultry was high in areas with high density of poultry, springtime, agricultural waters and WWTP discharge points. While wild birds and poultry were the main contributors to Campylobacter contamination in surface water, their contribution differed significantly by water type, season, and local poultry and ruminant densities