Bulk-fill materials show a similar or better performance than control flowable materials regarding interfacial integrity. However, some self-adhesive composites need improvements to achieve ...competitive performance.
Objective: This laboratory study compared the polymerization stress and gap formation of self-adhesive, bulk-fill and control flowable composites. The degree of conversion (DC) and post-gel shrinkage were also assessed.Methods: Two self-adhesive (Vertise Flow and Fusio Liquid Dentin), two bulk-fill (Tetric N-Flow Bulk-Fill and Filtek Bulk-Fill Flowable Restorative), and two control flowable (Z350 XT Flowable Restorative and Tetric N-Flow) composites were evaluated. Polymerization stress (PS) was determined in a universal testing machine (n=5). Gap formation was evaluated by scanning electron microscopy in class I restorations (n=6). DC was measured by Fourier transform infrared spectroscopy (n=3). Post-gel volumetric shrinkage (VS) was measured using the strain gauge method (n=5). Data were submitted to one-way analysis of variance or a Kruskal-Wallis test (α=0.05).Results: Vertise Flow and Fusio Liquid Dentin presented the highest interfacial gap (27%±5% and 21%±6%, respectively), which was associated with their highest PS (4.1±0.8 MPa and 3.5±0.6 MPa, respectively) and DC (63%±2% and 60%±2%, respectively) in spite of the lowest VS (1.0%±0.2% and 1.0%±0.3%, respectively). Tetric N-Flow Bulk-Fill and Filtek Bulk-Fill Flowable Restorative presented similar PS (2.9± 0.3 MPa and 2.4±0.2 MPa, respectively) to both control materials. However, the Tetric N-Flow Bulk-Fill showed the lowest gap (7%±2%) and the highest DC (64.3%±0.4%), and the Filtek Bulk-fill presented a marginal gap (17.8%±3.4%) and a DC (54.5%±2.7%) similar to the control materials. The VS values of both bulk-fill materials were similar to those of Tetric N-Flow and lower than that of Z350 XT Flowable Restorative.Conclusions: Bulk-fill composites showed either similar or significantly lower interfacial gaps and PS than the control flowable composites. The self-adhesive composites showed a significantly higher gap percentage and PS than the control and bulk-fill materials.
CPG 7909, a 24-mer B-Class CpG oligodeoxynucleotide (ODN), was tested for safety, tolerability and its ability to augment the immunogenicity of a commercial trivalent killed split influenza vaccine ...(Fluarix
® containing A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94; SmithKline Beecham) in a phase Ib blinded, randomized, controlled clinical trial. Sixty healthy volunteers were recruited in two consecutive cohorts of 30 subjects, who were randomly assigned to receive Fluarix plus 1
mg CPG 7909 or Fluarix plus saline control (15 subjects each). Vaccines were administered by intramuscular injection on a single occasion with subjects in the first cohort receiving a 1/10th dose of Fluarix and those in the second cohort receiving the full-dose. All safety measures including physical evaluation, laboratory blood assays, and assays for DNA autoimmunity were within normal values except for transient and clinically inconsequential decreases in total white blood cell counts in groups receiving CPG 7909. All vaccines were found to be generally well tolerated with similar frequency and intensity for most adverse reactions for groups receiving CPG 7909 as controls. Exceptions were injection site pain and headache, which were reduced in frequency in subjects receiving the 1/10th Fluarix dose without CpG, compared to the frequency in all other groups. There was a lack of pre-existing immunity, defined as hemagglutinin inhibition (HI) activity ≤20, for all subjects to the influenza strains A/Beijing/262/95 and B/Harbin/7/94 and for some subjects to A/Sydney/5/97. Post-vaccination humoral immune responses, as determined 2 and 4 weeks later by assay of HI activity and ELISA to detect antibodies against hemagglutinin (anti-HA) were similar for both full and reduced Fluarix doses but the cellular immune responses (measured as PBMC antigen-specific IFN-γ secretion) were reduced in the 1/10th Fluarix dose group. Humoral responses were not significantly enhanced by the addition of CPG 7909, except in individuals with pre-existing immunity to A/Sydney/5/97 strain (baseline HI activity titre >20), where there was a trend to higher HI activity with CPG 7909 (
P=0.06). The addition of CPG 7909 to the 1/10th dose of Fluarix did however result in significantly higher levels of IFN-γ secretion from peripheral blood mononuclear cells recovered at 4 weeks and restimulated ex vivo with A/Beijing/262/95 (
P=0.048) and B/Harbin/7/94 (
P=0.0057), restoring these to the level seen with full-dose vaccine. These results suggest that addition of CPG 7909 to Fluarix may allow the use of reduced vaccine doses without reduced immunogenicity.
Patients with amyotrophic lateral sclerosis (ALS) who are treated with the antiglutamatergic drug riluzole receive a fixed‐dose regimen of 50 mg b.i.d. The drug has been shown to increase ...tracheostomy‐free survival by 3–6 months. The pharmacokinetics of riluzole show a high interindividual variability. Riluzole serum concentrations are associated with side effects and ALS symptoms, but the effect of the actual blood level of riluzole on disease progression and survival is unknown. We measured trough and peak serum concentrations of riluzole in 160 patients with ALS, and estimated the area under the curve for one dosage interval (AUCi) using a Bayesian method. We then determined the association between riluzole AUCi and survival over a 5‐year period, and between riluzole AUCi and disease progression, defined by the rates of decline of arm strength and vital lung capacity. No significant association was found between riluzole AUCi and survival or disease progression.
Clinical Pharmacology & Therapeutics (2008); 83, 5, 718–722. doi:10.1038/sj.clpt.6100382
We present a case of orbital compartment syndrome (OCS) leading to monocular irreversible blindness following a pterional craniotomy for clipping of an anterior communicating artery aneurysm. OCS is ...an uncommon but vision-threatening entity requiring urgent decompression to reduce the risk of permanent visual loss. Iatrogenic orbital roof defects are a common finding following pterional craniotomies. However, complications related to these defects are rarely reported.
A 65-year-old female who underwent an anterior communicating artery clipping via a pterional approach 4 days before developed proptosis, ocular movement paresis, and irreversible visual impairment following an orthopedic surgery. Computed tomography images revealed an intraorbital cerebrospinal fluid (CSF) collection, which was evacuated via an acute recraniotomy. The next day, proptosis and intraorbital CSF collection on computed tomography images reoccurred and an oral and maxillofacial surgeon evacuated the collection via a blepharoplasty incision and blunt dissection. In addition, the patient was treated with acetazolamide and an external lumbar CSF drainage during 12 days. Hereafter, the CSF collection did not reoccur. Unfortunately, monocular blindness was persistent. We hypothesize the CSF collection occurred due to the combination of a postoperative orbital roof defect and a temporarily increased intracranial pressure during the orthopedic surgery.
We plead for more awareness of this severe complication after pterional surgeries and emphasize the importance of 1) strict ophthalmologic examination after pterional craniotomies in case of intracranial pressure increasing events, 2) immediate consultation of an oral and maxillofacial surgeon, and 3) consideration of CSF-draining interventions since symptoms are severely invalidating and irreversible within a couple of hours.
•Monocular irreversible blindness due to orbital compartment syndrome (OCS) following a ACoA aneurysm clipping.•OCS is an uncommon but vision-threatening entity requiring urgent decompression to reduce the risk of permanent visual loss.•Iatrogenic orbital roof defects are common following pterional craniotomies, however, rarely related to complications.•We suggest this catastrophic complication was elicited by temporary increased ICP during another surgery a few days postoperatively.
Here we describe a novel mechanism for plasma membrane insertion of the delta opioid receptor (DOR). In small dorsal root ganglion neurons, only low levels of DORs are present on the cell surface, in ...contrast to high levels of intracellular DORs mainly associated with vesicles containing calcitonin gene-related peptide (CGRP). Activation of surface DORs caused Ca
2+ release from IP
3-sensitive stores and Ca
2+ entry, resulting in a slow and long-lasting exocytosis, DOR insertion, and CGRP release. In contrast, membrane depolarization or activation of vanilloid and P2Y
1 receptors induced a rapid DOR insertion. Thus, DOR activation induces a Ca
2+-dependent insertion of DORs that is coupled to a release of excitatory neuropeptides, suggesting that treatment of inflammatory pain should include blockade of DORs.
We have analyzed a kinetic model for the formation of organic monolayers based on a previously suggested free radical chain mechanism for the reaction of unsaturated molecules with ...hydrogen-terminated silicon surfaces (Linford, M. R.; Fenter, P. M.; Chidsey, C. E. D. J. Am. Chem. Soc 1995, 117, 3145). A direct consequence of this mechanism is the nonexponential growth of the monolayer, and this has been observed spectroscopically. In the model, the initiation of silyl radicals on the surface is pseudo first order with rate constant, k i , and the rate of propagation is determined by the concentration of radicals and unreacted Si−H nearest neighbor sites with a rate constant, k p. This propagation step determines the rate at which the monolayer forms by addition of alkene molecules to form a track of molecules that constitute a self-avoiding random walk on the surface. The initiation step describes how frequently new random walks commence. A termination step by which the radicals are destroyed is also included. The solution of the kinetic equations yields the fraction of alkylated surface sites and the mean length of the random walks as a function of time. In mean-field approximation we show that (1) the average length of the random walk is proportional to (k p/k i )1/2, (2) the monolayer surface coverage grows exponentially only after an induction period, (3) the effective first-order rate constant describing the growth of the monolayer and the induction period (kt) is k = (2k i k p)1/2, (4) at long times the effective first-order rate constant drops to k i , and (5) the overall activation energy for the growth kinetics is the mean of the activation energies for the initiation and propagation steps. Monte Carlo simulations of the mechanism produce qualitatively similar kinetic plots, but the mean random walk length (and effective rate constant) is overestimated by the mean field approximation and when k p ≫ k i , we find k ∼ k i 0.7 k p 0.3 and E a = (0.7E i + 0.3E p). However the most striking prediction of the Monte Carlo simulations is that at long times, t ≫ 1/k, the effective first-order rate constant decreases to k i even in the absence of a chemical termination step. Experimental kinetic data for the reaction of undec-1-ene with hydrogen-terminated porous silicon under thermal reflux in toluene and ethylbenzene gave a value of k = 0.06 min-1 and an activation energy of 107 kJ mol-1. The activation energy is in reasonable agreement with density functional calculations of the transition state energies for the initiation and propagation steps.
Oligonucleotides have been synthesized on hydrogen-terminated Si(111) and porous silicon using surface hydrosilation of difunctional molecules (1,(omega)-dimethoxytritylundecenol) to produce a ...monolayer bearing suitable reactive groups to allow automated solid-phase DNA synthesis. The absence of an intervening oxide enables electrochemical characterisation of the surface-bound oligonucleotides. Complementary sequences to the DNA synthesized on Si(111) undergo hybridisation at the surface and a straightforward electrochemical quantitation of the amount of synthesized DNA and its hybridisation efficiency (47%) is possible using Ru(NH3)6(3+) as a redox label. In the case of DNA synthesized in porous silicon, electron transfer (ET) between DNA and the underlying bulk semiconductor can be studied by cyclic voltammetry, however the anisotropic diffusion inside the porous layer and the large resistance of the porous silicon results in voltammograms for which thin-layer behaviour is not observed and the peak currents increase with the square root of scan rate. We interpret these voltammograms in terms of charge transport limitations in the layer of metal centres bound to the DNA inside the pores. Further evidence for this interpretation has been obtained using scanning electrochemical microscopy (SECM) to study the charge transport between redox species in films of DNA synthesized on Si(111) surfaces that are in contact with an aqueous phase. As the bulk concentration of Ru(NH3)6(3+) is reduced below about 250 microM the SECM feedback indicates that the rate of charge transport between surface-bound Ru(NH3)6(3+) exceeds that due to diffusion in the liquid phase. Electrochemical quantitation of the DNA is not possible in this situation, however we have been able to obtain independent determinations using radioassay based on 32P or UV/VIS spectrophotometry of dimethoxytrityl cation cleaved from the porous layer. In the case of the former, use of labelled complementary sequences shows an inverse relationship between the current density used to prepare the porous silicon and the amount of hybridisation. This can be interpreted in terms of the specific surface area of the porous silicon layers since the hybridisation efficiencies (ca. 40%) obtained by comparing DMT+ cleaved from sequences synthesized on the surface and then from complementary sequences after hybridisation were relatively insensitive to the current density used to prepare the layers. Our recent work has also been concerned with individual Si nanocrystals generated by breaking up porous silicon during thermal hydrosilation reactions. FTIR spectroscopy shows these particles are also coated with an organic Si-C-bonded monolayer and they form stable, non-turbid and strongly luminescent (lambdamax = 600-650 nm) dispersions in apolar solvents (L. H. Lie, M. S. Duerdin, E. M. Tuite, A. Houlton and B. R. Horrocks, J. Electroanal. Chem., 2002, 538/539, 183). The effect of carrying out synthetic reactions on the porous silicon prior to breaking up the layer is to produce instead larger, micron-scale assemblies with a nanometre scale internal structure. Micron-sized particles of porous silicon produced by breaking up the layer can be probed by confocal Raman spectroscopy using the electric field of a focused laser to trap such particles. Although these particles are also luminescent, the use of relatively long wavelength laser excitation (lambda = 785 nm) allows acquisition of Raman spectra from individual particles in the optical trap. The bulk optical phonon mode at ca. 520 cm(-1) characteristic of crystalline silicon is red-shifted and broadened providing evidence for an internal nanometre scale substructure in these micron-sized particles and we also see evidence for this mode in the colloidal suspensions of the Si nanoparticles. We propose a model for the formation of these two types of particles and briefly discuss the prospects to extend our solid-phase synthesis on porous silicon to allow the facile synthesis of luminescent Si nanocrystals bearing DNA or other biomolecules.
We report a novel HBB: c.114G>C mutation in a Chinese family. This mutation resulted in a β37(C3)Trp→Cys amino acid substitution and was synonymous with Hb Kent, a hemoglobin (Hb) variant that was ...reported exclusively in patients of European descent. Though Hb Kent has a normal oxygen affinity and molecular stability, it has a characteristic dual variant appearance on cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC) caused by the posttranslational modification of cysteine. We also report the phenotypic expression of this variant when coinherited with the Southeast Asian (- -
SEA
) double α-globin gene deletion.