Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC. METHODS: We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. RESULTS: In 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P = .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P = .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year. CONCLUSIONS: In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.

Enhanced Photochromism of Diarylethene Induced by Excitation of Localized Surface Plasmon Resonance on Regular Arrays of Gold Nanoparticles.

Localized surface plasmon resonance (LSPR) excitation on the photochromic reaction of a diarylethene derivative (DE) was studied by surface enhanced Raman scattering (SERS). UV and visible light irradiations transform reversibly DE between open-form (OF) and closed-form (CF) isomers, respectively. A mixture of PMMA and DE (either OF or CF isomer) was spin-coated onto gold nanorods (GNRs) arrays, designed by electron beam lithography, with two localized surface plasmon resonances (LSPR) at distinct wavelengths, due to their anisotropy. The photochromic reaction rates from CF to OF isomers, under LSPR excitation, were monitored from SERS spectral changes under different polarizations, on the same GNR substrate to compare the effect of LSPR field strength. It appears that the photoisomerization rate was faster when LSPR was excited with the polarization parallel to the GNR long axis. The present results highlight a potential genuine mechanism, from near field LSPR excitation, involved in the photochromic enhancement of diarylethene photochromes.

Efficient Covalent Modification of Multiwalled Carbon Nanotubes with Diazotized Dyes in Water at Room Temperature.

Tetrafluoroborate salts of diazotized Azure A (AA-N2+), Neutral Red (NR-N2+) and Congo Red (CR-N2+) dyes were prepared and reacted with multiwalled carbon nanotubes (MWCNTs) at room temperature, in water without any reducing agent. The as-modified MWCNTs were examined by IRATR, Raman spectroscopy, XPS, TGA, TEM, and cyclic voltammetry. The diazonium band located at ∼2350 cm-1 in the diazotized dye IR spectra vanished after attachment to the nanotubes whereas the Raman D/G peak ratio slightly increased after dye covalent attachment at a high initial diazonium/CNT mass ratio. XPS measurements show the loss of F 1s from the BF4- anion together with a clear change in the high-resolution C 1s region from the modified nanotubes. Thermogravimetric analyses proved substantial mass loadings of the organic grafts leveling off at 40.5, 34.3, and 50.7 wt % for AA, NR, and CR, respectively. High-resolution TEM pictures confirmed the presence of 1.5-7-nm-thick continuous amorphous layers on the nanotubes assigned to the aryl layers from the dyes. Cyclic voltammetry studies in acetonitrile (ACN) confirmed the grafting of the dyes; the latter retain their electrochemical behavior in the grafted state. The experimental results correlate remarkably well with quantum chemical calculations that indicate high binding energies between the dyes and the CNTs accounting for true covalent bonding (140-185 kJ/mol with the CNT-aryl distance <1.6 nm), though attachment by π stacking also contributes to obtaining stable hybrids. Finally, the pH-responsive character of the robust hybrids was demonstrated by a higher degree of protonation of Neutral Red-grafted CNTs at pH 2 compared to that of the neutral aqueous medium. This work demonstrates that diazotized dyes can be employed for the surface modification of MWCNTs in a very simple and efficient manner in water and at room temperature. The hybrids could be employed for many purposes such as optically pH-responsive materials, biosensors, and optothermal composite actuators to name a few.

Highly stable silica-coated gold nanorods dimers for solution-based SERS.

The controlled assembly of anisotropic plasmonic nanoparticles (NPs) into highly SERS-active substrates remains particularly challenging for the production of long-term stable NP assemblies in suspension. In this work, we report a simple and efficient strategy to assemble gold nanorods (AuNRs) into dimers. The pH-dependent assembly was triggered using the bifunctional molecular linker BPE (1,2-bis(4-pyridyl)ethylene) and quenched with silver nitrate. The resulting AuNR dimers were encapsulated in mesoporous silica shell and proved to be stable in water for at least 5 months. Taking advantage of the large Raman scattering cross-section of the linker BPE, we conducted a detailed study of the enhancement ability of these NR dimers using solution-based surface enhanced Raman scattering (SERS). Both experimental (SERS) and theoretical (discrete dipole approximation) studies of the near-field characteristics revealed a two-orders of magnitude increase of the SERS enhancement factor for the dimers as compared to isolated AuNRs. Besides thermal and colloidal stability, mesoporous silica coating of AuNRs imparts other notable advantages due to its porosity and biocompatibility, which make these core-shell plasmonic platforms promising for future bio-applications.

Tunable Electromagnetic Coupling in Plasmonic Nanostructures Mediated by Thermoresponsive Polymer Brushes.

A smart and highly SERS-active plasmonic platform was designed by coupling regular arrays of nanotriangles to colloidal gold nanorods via a thermoresponsive polymer spacer (poly(N-isopropylacrylamide), PNIPAM). The substrates were prepared by combining a top-down and a bottom-up approach based on nanosphere lithography, surface-initiated controlled radical polymerization, and colloidal assembly. This multistep strategy provided regular hexagonal arrays of nanotriangles functionalized by polymer brushes and colloidal gold nanorods, confined exclusively on the nanotriangle surface. Interestingly, one could finely tune the gold nanorod impregnation on the polymer-coated nanostructures by adjusting the polymer layer thickness, leading to highly coupled plasmonic systems for intense SERS signal. Moreover, the thermoresponsive properties of the PNIPAM brushes could be wisely handled in order to monitor the SERS activity of the nanostructures coupled via this polymer spacer. The coupled hybrid plasmonic nanostructures designed in this work are therefore very promising smart platforms for the sensitive detection of analytes by SERS.

Oxadiazole-2-thiol adsorption on gold nanorods: a joint theoretical and experimental study by using SERS, XPS, and DFT.

The chemisorption of 1,3,4-oxadiazole-2-thiol (ODT) on gold nanorods has been investigated by using surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT). Although most of the SERS spectra have remarkable similarity to the normal Raman spectra of the pure analyte, the adsorption of ODT on a gold surface leads to a drastic change in its Raman spectrum and distinct vibrational features are obtained with gold nanorods and spherical nanoparticles. Simulated Raman spectra for hybrid systems that consist of an oxadiazole moiety coordinated to a Au20 gold cluster provided valuable information about the coordination mode and enabled us to assign vibration modes.

Microplastic leachates inhibit small-scale self-organization in mussel beds.

Self-organized spatial patterns are increasingly recognized for their contribution to ecosystem functioning. They can improve the ecosystem's ability to respond to perturbation and thus increase its resilience to environmental stress. Plastic pollution has now emerged as major threat to aquatic and terrestrial biota. Under laboratory conditions, we tested whether plastic leachates from pellets collected in the intertidal can impair small-scale, spatial self-organization and byssal threads production of intertidal mussels and whether the effect varied depending on where the pellets come from. Specifically, leachates originating from plastic pellets collected from relatively pristine and polluted areas respectively impaired and inhibited the ability of mussels to self-organize at small-scale and to produce byssal threads compared to control conditions (i.e., seawater without leaching solution). Limitations to natural self-organizing processes and threads formation may translate to a declined capacity of natural ecosystems to avoid tipping points and to a reduced restoration success of disturbed ecosystems.

Spectroelectrochemical characterization of small hemoproteins adsorbed within nanostructured mesoporous ITO electrodes.

3D nanostructured transparent indium tin oxide (ITO) electrodes prepared by glancing angle deposition (GLAD) were used for the spectroelectrochemical characterization of cytochrome c (Cyt c) and neuroglobin (Nb). These small hemoproteins, involved as electron-transfer partners in the prevention of apoptosis, are oppositely charged at physiological pH and can each be adsorbed within the ITO network under different pH conditions. The resulting modified electrodes were investigated by UV-visible absorption spectroscopy coupled with cyclic voltammetry. By using nondenaturating adsorption conditions, we demonstrate that both proteins are capable of direct electron transfer to the conductive ITO surface, sharing apparent standard potentials similar to those reported in solution. Preservation of the 3D protein structure upon adsorption was confirmed by resonance Raman (rR) spectroscopy. Analysis of the derivative cyclic voltabsorptograms (DCVA) monitored either in the Soret or the Q bands at scan rates up to 1 V s(-1) allowed us to investigate direct interfacial electron transfer kinetics. From the DCVA shape and scan rate dependences, we conclude that the interaction of Cyt c with the ITO surface is more specific than Nb, suggesting an oriented adsorption of Cyt c and a random adsorption of Nb on the ITO surface. At the same time, Cyt c appears more sensitive to the experimental adsorption conditions, and complete denaturation of Cyt c may occur as evidenced from cross-correlation of rR spectroscopy and spectroelectrochemistry.

Surface-enhanced Raman scattering on silver nanostructured films prepared by spray-deposition.

Silver nanostructured films were directly prepared by spray deposition of preformed polyol-based Ag-PVP nanoparticles. These homogeneous films of high optical quality were tested as SERS-active substrates. Laser excitation at 514.5 nm within the red part of the plasmon band leads to intense and reproducible SERS spectra of acridine, used as the probe molecule. From SERS measurements at different pH values, it was possible to determine the apparent pK(a) of acridine and to obtain specific surface properties of the film. Finally, these SERS titrations along with enhancement factor estimates allowed us to further depict the nature of the films.

Star-Shaped Fe3-xO4-Au Core-Shell Nanoparticles: From Synthesis to SERS Application.

In this work, the preparation of magneto-plasmonic granular nanostructures and their evaluation as efficient substrates for magnetically assisted surface enhanced Raman spectroscopy (SERS) sensing are discussed. These nanostructures consist of star-shaped gold Au shell grown on iron oxide Fe3-xO4 multicores. They were prepared by seed-mediated growth of anisotropic, in shape gold nanosatellites attached to the surface of polyol-made iron oxide polycrystals. In practice, the 180 nm-sized spherical iron oxide particles were functionalized by (3-aminopropyl) triethoxysilane (APTES) to become positively charged and to interact, in solution, with negatively charged 2 nm-sized Au single crystals, leading to nanohybrids. These hybrids acted subsequently as nucleation platforms for the growth of a branched gold shell, when they were contacted to a fresh HAuCl4 gold salt aqueous solution, in the presence of hydroquinone, a reducing agent, for an optimized nominal weight ratio between both the starting hybrids and the gold salt. As expected, the resulting nanocomposites exhibit a high saturation magnetization at room temperature and a rough enough plasmonic surface, making them easily attracted by a lab. magnet, while exhibiting a great number of SERS hot spots. Preliminary SERS detection assays were successfully performed on diluted aqueous thiram solution (10-8 M), using these engineered substrates, highlighting their capability to be used as chemical trace sensors.

Surface Enhanced Raman Scattering on Regular Arrays of Gold Nanostructures: Impact of Long-Range Interactions and the Surrounding Medium.

Long-range interaction in regular metallic nanostructure arrays can provide the possibility to manipulate their optical properties, governed by the excitation of localized surface plasmon (LSP) resonances. When assembling the nanoparticles in an array, interactions between nanoparticles can result in a strong electromagnetic coupling for specific grating constants. Such a grating effect leads to narrow LSP peaks due to the emergence of new radiative orders in the plane of the substrate, and thus, an important improvement of the intensity of the local electric field. In this work, we report on the optical study of LSP modes supported by square arrays of gold nanodiscs deposited on an indium tin oxyde (ITO) coated glass substrate, and its impact on the surface enhanced Raman scattering (SERS) of a molecular adsorbate, the mercapto benzoic acid (4-MBA). We estimated the Raman gain of these molecules, by varying the grating constant and the refractive index of the surrounding medium of the superstrate, from an asymmetric medium (air) to a symmetric one (oil). We show that the Raman gain can be improved with one order of magnitude in a symmetric medium compared to SERS experiments in air, by considering the appropriate grating constant. Our experimental results are supported by FDTD calculations, and confirm the importance of the grating effect in the design of SERS substrates.

Glycemic Control in Adult Surgical Patients Receiving Regular Insulin Added to Parenteral Nutrition vs Insulin Glargine: A Retrospective Chart Review.

BACKGROUND: Hyperglycemia is a frequent complication in patients receiving parenteral nutrition (PN) and has been associated with an increased risk of mortality. Treatment of hyperglycemia requires insulin therapy; however, the optimal dose and route have not been established. This study aimed to compare regular insulin added to PN (RI-in-PN) with subcutaneous insulin glargine for the management of hyperglycemia in patients receiving PN. METHODS: This retrospective study was conducted at a tertiary medical center and reviewed 113 adult, non-critically ill surgical patient admissions receiving PN over a 5-year period. The primary outcome was achievement of glycemic control. Secondary outcomes were time to glycemic control, hypoglycemic events, hospital length of stay, and 1-year mortality. RESULTS: The RI-in-PN group had a significantly higher percentage of patient admissions who achieved glycemic control compared with the insulin glargine group (71.8% vs 48.6%, P = 0.017). There was no difference in time to glycemic control, hypoglycemic events, hospital length of stay, or 1-year mortality between groups. Among patients with diabetes mellitus (DM), however, the insulin glargine group had a significantly higher percentage of admissions with at least 1 hypoglycemic event (45.5% vs 20%, P = 0.035). CONCLUSIONS: RI-in-PN is recommended over insulin glargine because of the higher likelihood of achieving glycemic control and, in patients with DM, lower risk of hypoglycemic events. Large, randomized controlled trials are needed to further guide prescribing practice.

Assembly of gold nanoparticles using turnip yellow mosaic virus as an in-solution SERS sensor.

A common challenge in nanotechnology is the conception of materials with well-defined nanoscale structure. In recent years, virus capsids have been used as templates to create a network to organize 3D nano-objects, building thus new functional nanomaterials and then devices. In this work, we synthetized 3D gold nanoclusters and we used them as Surface Enhanced Raman Scattering (SERS) sensor substrates in solution. In practice, gold nanoparticles (AuNPs) were grafted on turnip yellow mosaic virus (TYMV) capsid, an icosahedral plant virus. Two strategies were considered to covalently bind AuNPs of different sizes (5, 10 and 20 nm) to TYMV. After purification by agarose electrophoresis and digestion by agarase, the resulting nano-bio-hybrid AuNP-TYVM was characterized by different tools. Typically, dynamic light scattering (DLS) confirmed the grafting through the hydrodynamic size increase by comparing AuNPs alone to AuNP-TYMV (up to 33, 50 and 68 nm for 5, 10 and 20 nm sized AuNPs, respectively) or capsids alone (28 nm). Transmission electronic microscopy (TEM) observations revealed that AuNPs were arranged with 5-fold symmetry, in agreement with their grafting around icosahedral capsids. Moreover, UV-vis absorption spectroscopy showed a red-shift of the plasmon absorption band on the grafted AuNP spectrum (530 nm) compared to that of the non-grafted one (520 nm). Finally, by recording in solution the Raman spectra of a dissolved probe molecule, namely 1,2-bis(4-pyridyl)ethane (BPE), in the presence of AuNP-TYVM and bare AuNPs or capsids, a net enhancement of the Raman signal was observed when BPE is adsorbed on AuNP-TYVM. The analytical enhancement factor (AEF) value of AuNP-TYMV is 5 times higher than that of AuNPs. These results revealed that AuNPs organized around virus capsid are able to serve as in-solution SERS-substrates, which is very interesting for the conception of ultrasensitive sensors in biological media.

Regioselective surface functionalization of lithographically designed gold nanorods by plasmon-mediated reduction of aryl diazonium salts.

Site-selective surface functionalization of anisotropic gold nanoparticles represents a major breakthrough for fully exploiting nanoparticle anisotropy. In this paper, we explore an original strategy for the regioselective functionalization of lithographically designed gold nanorods (AuNRs), based a combination of photo-induced plasmon excitation and aryl diazonium salt chemistry.

Oriented Gold Nanorods and Gold Nanorod Chains within Smectic Liquid Crystal Topological Defects.

We show that the use of oriented linear arrays of smectic A defects, the so-called smectic oily streaks, enables the orientation of gold nanorods (GNRs) for a large range of GNR diameters, ranging from 7 to 48 nm, and for various ligands. For the small GNRs it enables oriented end-to-end small chains of GNRs when the density is increased from around 2 GNRs/µm2 to around 6 GNRs/µm2. We have characterized the orientation of single GNRs by spectrophotometry and two-photon luminescence (TPL). A strongly anisotropic absorption of the composites and an on-off switching of GNR luminescence, both controlled by incident light polarization, are observed, revealing an orientation of the GNRs mostly parallel to the oily streaks. A more favorable trapping of GNRs by smectic dislocations with respect to ribbon-like defects is thus demonstrated. The dislocations appear to be localized at a specific localization, namely, the summit of rotating grain boundaries. Combining plasmonic absorption measurements, TPL measurements, and simulation of the plasmonic absorption, we show that the end-to-end GNR chains are both dimers and trimers, all parallel to each other, with a small gap between the coupled GNRs, on the order of 1.5 nm, thus associated with a large red-shift of 110 nm of the longitudinal plasmonic mode. A motion of the GNRs along the dislocations appears as a necessary ingredient for the formation of end-to-end GNR chains, the gap value being driven by the balance between the attracting van der Waals interactions and the steric repulsion between the GNRs and leading to interdigitation of the neighboring ligands. We thus obtain electromagnetic coupling of nanorods controlled by light polarization.

Water-soluble plasmonic nanosensors with synthetic receptors for label-free detection of folic acid.

We describe an original approach to graft molecularly imprinted polymers around gold nanorods by combining the diazonium salt chemistry and the iniferter method. This chemical strategy enables fine control of the imprinting process at the nanometer scale and provides water-soluble plasmonic nanosensors.

Extension of Drosophila lifespan by cinnamon through a sex-specific dependence on the insulin receptor substrate chico.

Cinnamon is a spice commonly used worldwide to flavor desserts, fruits, cereals, breads, and meats. Numerous health benefits have been attributed to its consumption, including the recent suggestion that it may decrease blood glucose levels in people with diabetes. Insulin signaling is an integral pathway regulating the lifespan of laboratory organisms, such as worms, flies, and mice. We posited that if cinnamon truly improved the clinical signs of diabetes in people that it would also act on insulin signaling in laboratory organisms and increase lifespan. We found that cinnamon did extend lifespan in the fruit fly, Drosophila melanogaster. However, it had no effect on the expression levels of the 3 aging-related Drosophila insulin-like peptides nor did it alter sugar, fat, or soluble protein levels, as would be predicted. In addition, cinnamon exhibited no protective effects in males against oxidative challenges. However, in females it did confer a protective effect against paraquat, but sensitized them to iron. Cinnamon provided no protective effect against desiccation and starvation in females, but sensitized males to both. Interestingly, cinnamon protected both sexes against cold, sensitized both to heat, and elevated HSP70 expression levels. We also found that cinnamon required the insulin receptor substrate to extend lifespan in males, but not females. We conclude that cinnamon does not extend lifespan by improving stress tolerance in general, though it does act, at least in part, through insulin signaling.

Extension of Drosophila lifespan by Rhodiola rosea through a mechanism independent from dietary restriction.

Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR) that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2) proteins, insulin and insulin-like growth factor signaling (IIS), and the target of rapamycin (TOR). In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.

Template-assisted deposition of CTAB-functionalized gold nanoparticles with nanoscale resolution.

In this paper, we demonstrate the template-assisted deposition of cetyltrimethylammonium bromide (CTAB) stabilized gold nanorods at lithographically defined positions on a substrate. Overcoating of the nanoparticles with polystyrenesulfonate allows to switch the original nanoparticles positive surface charge to negative and to apply the template-assisted deposition technique developed for citrate-capped gold nanoparticles also to CTAB stabilized nanoparticles. The successful, selective deposition of gold nanorods in trenches with widths down to 50 nm is demonstrated. Our results indicate the potential of this method for the fabrication of well controlled, reproducible plasmonic biosensing substrates, applicable to the vast palette of anisotropic nanoparticle shapes synthesized with CTAB as the templating agent.