Electronic Outpatient Referral System for Liver Transplant Improves Appropriateness and Allows First Visit Triage.

BACKGROUND & AIMS: Missed or inappropriate referrals of potential candidates for liver transplantation (LT) are common and traditional referral methods (tRs) do not allow for efficient triage. We investigated the effects of a website developed for electronic outpatient referral to LT (eRW-LT) on these issues. METHODS: We prospectively collected data on all consecutive outpatient referrals to 2 Italian LT centers from January 2015 to December 2019. In the second half of the study, starting from July 2017, referring physicians had the option of using eRW-LT, quickly obtaining the judgment on the appropriateness and urgency of the visit from a transplant hepatologist. RESULTS: In the second half of the study, there were 99 eRW-LTs and 96 traditional referrals (new tRs), representing a 17.4% increase over the 161 traditional referrals (old tRs) of the first half. With eRW-LT, 11.1% of referrals were judged inappropriate online without booking a visit. Appropriateness, judged at the time of the first visit, was 59.6%, 56.2%, and 94.3% with old tRs, new tRs, and eRW-LT, respectively. Considering the appropriate visits, the median waiting time in days between referral date and first visit appointment was significantly shorter for urgent visits referred with eRW-LT (5.0; 95% CI, 4.8-9.3) compared with nonurgent visits sent with the same system (17.0; 95% CI, 11.5-25.0; P < .0001), those referred with old tRs (14.0; 95% CI, 8.0-23.0; P < .001) and with new tRs (16.0; 95% CI, 10.0-23.0; P < .001). CONCLUSIONS: eRW-LT allows an increase in the number of referrals for LT, ensuring effective triage and better appropriateness of visits.

Rationalization of dye uptake on titania slides for dye-sensitized solar cells by a combined chemometric and structural approach.

A model photosensitizer (D5) for application in dye-sensitized solar cells has been studied by a combination of XRD, theoretical calculations, and spectroscopic/chemometric methods. The conformational stability and flexibility of D5 and molecular interactions between adjacent molecules were characterized to obtain the driving forces that govern D5 uptake and grafting and to infer the most likely arrangement of the molecules on the surface of TiO2. A spectroscopic/chemometric approach was then used to yield information about the correlations between three variables that govern the uptake itself: D5 concentration, dispersant (chenodeoxycholic acid; CDCA) concentration, and contact time. The obtained regression model shows that large uptakes can be obtained at high D5 concentrations in the presence of CDCA with a long contact time, or in absence of CDCA if the contact time is short, which suggests how dye uptake and photovoltaic device preparation can be optimized.

Structural characterization and thermal and chemical stability of bioactive molecule-hydrotalcite (LDH) nanocomposites.

Layered double hydroxides (LDH) are versatile materials used for intercalating bioactive molecules, both in pharmaceutical and cosmetic fields, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability, and/or obtaining modified release properties. The properties of the intercalation compounds of Mg/Al_LDH and Zn/Al_LDH with different drugs and sunscreens, namely diclofenac, ketoprofen, gliclazide, retinoic acid, furosemide, para-aminobenzoic acid and 2-phenylbenzimidazolsulfonic (Eusolex) acid, have been studied by crystallographic, spectroscopic and thermogravimetric techniques and by solid state NMR, to shed light on their structure, their molecular interactions and their stability from the thermal and chemical viewpoint. The structural features were described with particular attention to the interaction between the organic and inorganic components and to the stability of the intercalation products. For the first time two synchrotron radiation powder diffraction patterns of organic-containing LDH were solved and refined by Rietveld methods to obtain an experimental crystal structure.

Asymmetric synthesis of trisubstituted tetrahydrothiophenes bearing a quaternary stereocenter via double Michael reaction involving dynamic kinetic resolution.

The stereoselective synthesis of highly functionalized tetrahydrothiophenes bearing three contiguous stereocenters, one of them quaternary, can be achieved by reacting trans-α-cyano-α,ß-unsaturated ketones and trans-tert-butyl 4-mercapto-2-butenoate in the presence of a readily available amine thiourea. The products are obtained in high yield, good diastereoselectivity, and excellent enantioselectivity. The overall formation of tetrahydrothiophenes occurs via a cascade double Michael reaction involving a highly efficient process of dynamic kinetic resolution.

Noncovalent organocatalytic synthesis of enantioenriched terminal aziridines with a quaternary stereogenic center.

A high-yielding and enantioselective access to novel N-Boc terminal aziridines, bearing a quaternary stereogenic center, has been developed via an aza-Michael initiated ring-closure (aza-MIRC) reaction of α-acyl acrylates with an N-tosyloxy tert-butyl carbamate catalyzed by a chiral amino thiourea. The feasibility of the aziridine regioselective ring-opening to valuable α,α-disubstituted α-amino acid esters has been demonstrated.

The use of a ditopic Gd(III) paramagnetic probe for investigating α-bungarotoxin surface accessibility.

Protein surface accessibility is a critical parameter which drives all intermolecular interaction processes. In this respect a big deal of information has been derived by analyzing paramagnetic perturbation profiles obtained from NMR protein spectra, particularly in the case that the effects due to different soluble paramagnets can be compared. Here Gd(2)L7, a neutral ditopic paramagnetic NMR probe, has been characterized in terms of structure and relaxivity and its paramagnetic perturbations on α-bungarotoxin CαH signals in ((1))H-((13))C HSQC (heteronuclear single quantum coherence) spectra have been analyzed. Then, these signal attenuations have been compared with the ones previously obtained in the presence of GdDTPA-BMA (gadolinium(III) diethylenetriamine-N,N,N',N'",N"-pentaacetate-bis(methylamide)). In spite of the different molecular size and shape, for the two probes a common pathway of approach to the α-bungarotoxin surface can be observed with an equally enhanced access of both GdDTPA-BMA and Gd(2)L7 toward the protein surface side where residues involved in the receptor binding are located. The different residence times of the water molecule directly coordinated by the Gd(III) ion measured for the two paramagnets account for the reduced broadening of water signal in the presence of the ditopic probe at equivalent gadolinium concentration. These features make Gd(2)L7 a very suitable probe for investigating protein surface accessibility of complex protein systems.

Highly enantioselective epoxidation catalyzed by cinchona thioureas: synthesis of functionalized terminal epoxides bearing a quaternary stereogenic center.

A brilliant debut! Cinchona thioureas have been reported for the first time as catalysts in the area of asymmetric oxidations. They efficiently promote an unprecedented highly enantioselective epoxidation of deactivated 1,1-disubstituted alkenes to terminal epoxides containing a quaternary stereogenic center (see scheme).

In vitro release kinetics and physical, chemical and mechanical characterization of a POVIAC®/CaCO3/HAP-200 composite.

Coralline calcium-hydroxyapatite and calcium carbonate from Porites Porites coral were added to a polymeric matrix based on polyvinyl acetate (POVIAC(®)), to obtain a novel bone substitute composite as well as a system for the controlled drug (cephalexin) release. Composite samples with different compositions were characterized by physical-chemical and mechanical methods. Furthermore, the in vitro release profile of cephalexin and the kinetic behavior of its release from these composites were analyzed by appropriate mathematical models. It was shown that there is no chemical interaction between the inorganic filler and the polymer matrix, each conserving the original properties of the raw materials. The compressive mechanical strength and Young modulus of the composite with 17.5% of POVIAC(®), has better mechanical properties than those of cancellous bone. The variation of POVIAC(®) content can affect the cephalexin release kinetic in the composite. The cephalexin release mechanism from the composites can be considered as the result of the joint contribution of a prevailing Fickian diffusion and of polymer chain relaxation. It was also demonstrated that cephalexin is occluded inside the composites and not on their surface.

Multi-component, regio-selective aldol addition of ß-ketoesters to aldehydes: scope and applications.

Simple and effective multi-component one-pot aldol addition/protection reactions of ß-ketoesters to a series of aldehydes in the presence Me(3)SiCl and i-Pr(2)EtN have been described. The analysis of the scope of the reaction revealed a dramatic dependence of the reactivity on the substrates used. Thus the effect of a catalytic amount of DMF and different reaction conditions was widely investigated. Further transformations of the aldol adducts were particularly useful to give valuable diols and compounds with quaternary stereocenters, while X-ray structural analysis gave also important stereochemical information about this challenging reaction.

Asymmetric synthesis of ethoxydienamines in superbasic medium mediated by chiral sulfinyl group.

The direct addition of metalated alkoxydiene 2, obtained from α,ß-unsaturated acetal 1 through a LIC-KOR-promoted conjugated elimination reaction, to enantiopure sulfinimines 3 (both R and SN-sulfinyl imines) afforded N-sulfinyl alkoxydienyl amines 4 with high diastereoselectivity. Functionalized enantiopure alkoxydienyl amines 5 were then easily obtained upon the selective removal of the chiral auxiliary under mild conditions. Moreover, the further hydrolysis of the alkoxydienyl moiety gave access to protected enantiopure ß-keto amines 7.

Understanding the physico-chemical properties of polyhedral oligomeric silsesquioxanes: a variable temperature multidisciplinary study.

This work is focused on a multidisciplinary study of a completely condensed octaisobutyl-silsesquioxane (IBUPOSS) as a model of the alkyl POSS family. IBUPOSS is characterized by the presence of eight isobutyl groups bonded to the corners of the siliceous framework. Differential scanning calorimetric measurements and an innovative simultaneous in situ Raman/XRPD experiment suggested that IBUPOSS undergoes a solid phase transition around 330 K, and indicated that this transition is related to a change in the conformational freedom of the isobutyl chains. The X-ray powder diffraction (XRPD) pattern of the high temperature phase was indexed in the high symmetry [R3m] space group. The Raman data indicated a larger mobility of the aliphatic side chains at high temperature, thus inducing a disorder in the IBUPOSS moiety. Multidimensional heteronuclear solid-state NMR experiments were employed to probe the structural and motional features of the observed phase transition. The various conformations can be accounted for by a pseudo-D(3h) symmetry able to obey to the [R3m] space group. Simulations on molecular mechanics and dynamics, together with quantum-chemical calculations, confirmed this hypothesis and gave some hints on the conformational mobility and the energetic features of IBUPOSS, a base material with relevant applications in catalysis and polymer science.

A combined high-resolution X-ray powder diffraction, computational, and XPS study of the local structure of extra-framework copper ions in over-exchanged Cu-MCM22 zeolite.

Local structure and site distribution of extra-framework copper ions in over-exchanged Cu-MCM22 zeolite were determined by a combination of high resolution X-ray powder diffraction and computational analysis. X-ray diffraction data suggested the presence of three Cu sites in six-membered rings and one site in a five-membered ring close to the interlamellar region, inside the MCM-22 supercage, whereas no Cu ions were found within the sinusoidal channels. First principle molecular orbital DFT calculations were employed to obtain, for the first time, an accurate structural description of the Cu(I) sites in the supercage, adding a structural and energetic interpretation to previous IR and EPR studies. The combined experimental and computational study suggested that Cu(I) sites facing 6-MRs are particularly stable. In general 5- or 4-fold coordination sites are located in 6-MRs while 2- or 3-fold coordination sites are located in 5-MRs. Three preferentially occupied sites were found in copper-exchanged MCM-22. X-ray photoelectron spectroscopy suggested the formation of dispersed Cu close to the surface of MCM-22 crystallites, easily reduced to Cu(I) under ultrahigh vacuum conditions.

A mesoporous pattern created by nature in spicules from Thetya aurantium sponge.

Siliceous or carbonate spicules provide support and defense to marine sponges. The inorganic envelope usually embodies a protein core. Our SAXS study of the siliceous spicules from the demosponge Thetya aurantium proves the very ordered structure assumed by the protein core inside the spicules. Indeed, not only the very sharp diffraction spots already found in previous studies on spicules from different sponges are confirmed, but also the 11 sharp spots in the diffraction pattern recorded after thermal treatment at 250 degrees C can only be interpreted in terms of a natural nanocomposite mesostructure with an hexagonal lattice formed by a three-dimensional periodic arrangement of silica cages in which the protein units act as structure directing agent.

The increase of iron phytoavailability in soils ammended with paper mill sludge.

In soils characterized by low organic matter and high pH values (7.5-8.59) iron availability to plants is limited even if the content of total Fe(III) is high. We have studied by Hordeum distichum plants the capability of paper mill sludge to increase the iron phytoavailable fraction in an alkaline soil. The effect of paper mill sludges adding to an iron-deficient soil was evaluated both considering the phyto-available fraction of iron and the distribution of organic carbon (hydrophobic, fulvic and humic carbon) in the soil before and after sludge adding. Iron concentration was determined in the different portions of Hordeum distichum plants grown on soils with and without paper mill sludges. Application of paper mill sludge induces an increase in the concentration of available Fe. This effect is probably due to the production of Fe chelators by soil microorganisms acting on sludge organic matter. The Fe chelators produced result in the solubilization of not soluble Fe-complexes present in the soil.

Structural characterization of siliceous spicules from marine sponges.

Siliceous sponges, one of the few animal groups involved in a biosilicification process, deposit hydrated silica in discrete skeletal elements called spicules. A multidisciplinary analysis of the structural features of the protein axial filaments inside the spicules of a number of marine sponges, belonging to two different classes (Demospongiae and Hexactinellida), is presented, together with a preliminary analysis of the biosilicification process. The study was carried out by a unique combination of techniques: fiber diffraction using synchrotron radiation, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetric (DSC), Fourier transform infrared spectroscopy (FTIR), and molecular modeling. From a phylogenetic point of view, the main result is the structural difference between the dimension and packing of the protein units in the spicule filaments of the Demospongiae and the Hexactinellida species. Models of the protein organization in the spicule axial filaments, consistent with the various experimental evidences, are given. The three different species of demosponges analyzed have similar general structural features, but they differ in the degree of order. The structural information on the spicule axial filaments can help shed some light on the still unknown molecular mechanisms controlling biosilicification.

Fiber diffraction study of spicules from marine sponges.

A synchrotron radiation fiber diffraction structural study of the axial filament of siliceous spicules from two species of marine sponges (the Demosponge Geodia cydonium and the Hexactinellid Scolymastra joubini) was carried out. The sharpness of the spots in the diffraction patterns indicated that the protein units in the filament of both samples were highly organized. A possible explanation is that the arrangement of the protein units is similar to that of the pores in highly ordered siliceous mesoporous materials. Nevertheless, the diffraction patterns are quite different for the two types of spicules. The pattern of G. cydonium is consistent with a regular 2D hexagonal lattice of protein units in the direction perpendicular to the spicule axis, with a repeating distance of 5.8 nm; the units are linked to form fibers along the axis. The pattern of S. joubini indicates the presence of two different 2D lattices in which the repeating protein units are inclined by +50 degrees and -50 degrees with respect to the elongation axis; the distance between the units increases to 8.4 nm. This 2D model is consistent with hexagonal packing of spirally oriented cylindrical protein units elongated along the filament axis.