EEG quality during simultaneous functional MRI of interictal epileptiform discharges

This article concerns the evaluation of the quality of interictal epileptiform EEG discharges recorded throughout simultaneous echo planar imaging (EPI). BOLD (blood oxygen level dependent) functional MRI (fMRI) images were acquired continuously on a patient with intractable epilepsy. EEG was sampled simultaneously, during and after imaging, with removal of pulse and imaging artifacts by subtraction of channel-specific running averages. Contiguous EEG epochs recorded with and without fMRI (fMRI+ve vs. fMRI−ve) were next randomized and presented to two blinded observers. Epileptiform discharges were identified retrospectively, and comparison was made in terms of the number of identified events, their amplitude, and spatiotemporal distribution. A spectral analysis was also performed on the EEG. In the randomized comparison of EEG segments, 80 (fMRI+ve) vs. 69 (fMRI−ve) discharges were noted with good interobserver agreement (69%). There were no significant differences in amplitude or spatio-temporal distribution. Comparison of the events detected and measured by two expert observers demonstrated that the Interictal Epileptiform Discharge (IED) characteristics were indistinguishable with and without scanning. We review briefly the existing literature on EEG recording quality for combined EEG/fMRI.     

Electronic excitations induced by hydrogen surface chemical reactions on gold

Associated with chemical reactions at surfaces energy may be dissipated exciting surface electronic degrees of freedom. These excitations are detected using metal-insulator-metal (MIM) heterostructures (Ta-TaOx-Au) and the reactions of H with and on a Au surface are probed. A current corresponding to 5×10(-5) electrons per adsorbing H atom and a marked isotope effect are observed under steady-state conditions. Analysis of the current trace when the H atom flux is intermitted suggests that predominantly the recombination reaction creates electronic excitations. Biasing the front versus the back electrode of the MIM structure provides insights into the spectrum of electronic excitations. The observed spectra differ for the two isotopes H and D and are asymmetric when comparing negative and positive bias voltages. Modeling indicates that the excited electrons and the concurrently created holes differ in their energy distributions.     

Synthesis of Tris(pentafluoroethyl)germanes

The synthesis of tris(pentafluoroethyl)germanium derivatives is described. The reaction of germanium tetrachloride with three equivalents of the pentafluoroethylation reagent LiC₂F₅ does not lead selectively to the formation of tris(pentafluoroethyl)chlorogermane, (C₂F₅)₃GeCl. Here the introduction of a diethylamino function as a protecting group was beneficial. Thus, treatment of Cl₃GeNEt₂ with LiC₂F₅ smoothly afforded (C₂F₅)₃GeNEt₂. The replacement of the amino substituent by halides was accomplished by reaction with HBr or HCl on a multigram scale. The combination of (C₂F₅)₃GeCl with Ag₂CO₃ gave rise to the formation of the digermoxane [(C₂F₅)₃Ge]₂O. An obtuse Ge‐O‐Ge angle of 150.2(1)° was determined by X‐ray diffraction. Attempted hydrolysis of the digermoxane leads to an equilibrium mixture of the precursor, (C₂F₅)₃GeOH, and water.     

Inherent Stability Limits of Intramolecular Boron Nitrogen Lewis Acid–Base Pairs

The reaction of (C₆F₅)₂BH ( 1 ) with N,N‐dimethylallylamine ( 2 ), N,N‐diethylallylamine ( 3 ) and 1‐allylpiperidine ( 4 ) afforded the five‐membered ring systems (C₆F₅)₂B(CH₂)₃NR₂ (R=Me ( 5 ), Et ( 6 )) and (C₆F₅)₂B(CH₂)₃N(CH₂)₅ ( 7 ) with an intramolecular dative B? N bond. A different product was obtained from the reaction of (C₆F₅)₂BH ( 1 ) with N,N‐diisopropylallylamine ( 8 ), which afforded the seven‐membered ring system (C₆F₅)₂B(CH₂)₃N(iPr)CH(Me)CH₂ ( 9 ) under extrusion of dihydrogen. All compounds were characterised by elemental analysis, NMR spectroscopy and single‐crystal X‐ray diffraction experiments. Density functional theory (DFT) studies were performed to rationalise the different reaction mechanism for the formation of products 6 and 9 . The bonding situation of compound 9 was analysed in terms of its electron density topology to describe the delocalised nature of a borane– enamine adduct.     

Dialkylaluminium‐, ‐Gallium‐, and ‐Indium‐Based Poly‐Lewis Acids with a 1,8‐Diethynylanthracene Backbone

Potential host systems based on a rigid 1,8‐diethynylanthracendiyl backbone were synthesised by treatment of 1,8‐diethynylanthracene with the Group 13 trialkyls AlMe₃, GaMe₃, InMe₃, AlEt₃ and GaEt₃. The resulting products were characterised by IR and multinuclear NMR spectroscopy, elemental analyses and determination of their crystal structures by X‐ray diffraction. The compounds are dimeric in the solid state and comprise two M₂C₂ heterocycles. Depending on the steric demand of the alkyl substituents at the metal atom, different types of binding modes were observed, which can be classified to lie between the ideals of side‐on coordination with almost linear primary M? C?C units and the 3c–2e coordination with symmetrically bridging alkynyl units in M‐C‐M bonds. As a solution in THF the dimers are broken into monomers and some are found to undergo ligand scrambling reactions.     

Development and validation of a liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of tamoxifen, anastrozole, and letrozole in human plasma and its application to a clinical study

There is substantial evidence that circulating estrogens promote the proliferation of breast cancer. Consequently, adjuvant hormonal treatment strategies targeting estrogen action have been established. Such hormonal therapies include selective estrogen receptor modulators, such as tamoxifen, which interfere at the estrogen receptors directly, or non-steroidal aromatase inhibitors, such as anastrozole and letrozole, which inhibit estrogen synthesis through blocking the aromatase, a key enzyme of estrogen production. Despite considerable therapeutic success, in several cases, the use of these drugs is limited by side effects that have been described to significantly impair the adherence of patients to endocrine treatment. However, objective data concerning patient adherence and its clinical relevance are limited. One promising approach to check patient-reported adherence is drug monitoring in human plasma. Therefore, a liquid chromatography–tandem mass spectrometry method to determine the plasma concentrations of tamoxifen, anastrozole, and letrozole has been developed and fully validated according to guidelines for clinical and forensic toxicology. The validation criteria evaluated were selectivity, linearity, accuracy and precision, limit of quantification, recovery and matrix effects, sample stability, and carryover. The six-point calibration curves showed linearity over the range of concentrations from 25 to 500 ng/ml for tamoxifen, 5 to 200 ng/ml for anastrozole, and 10 to 300 ng/ml for letrozole. The intra- and inter-day precision and accuracies were always better than 15%. The validated procedure was successfully applied to a clinical study (Patient-Reported Outcomes in Breast Cancer Patients undergoing Endocrine Therapy, PRO-BETh). A major aim of PRO-BETh study is the comprehensive evaluation of adherence to treatment in pre- and post-menopausal women with breast cancer. Plasma samples of 310 breast cancer patients undergoing anti-estrogen therapy were analyzed. Eight samples did not contain a quantifiable amount of drug, strongly indicating non-adherence of the corresponding patients to adjuvant breast cancer treatment. Furthermore, plasma concentrations at the lower end of the observed plasma level distribution might represent a hint but not a confirmation for non-adherence in terms of non-daily and irregular intake of the prescribed drug.     

On the correlation between hydrophobicity, liposome binding and cellular uptake of porphyrin sensitizers

A crucial factor in choosing a porphyrin or analogous photosensitizer for photodynamic therapy (PDT) is its ability to incorporate into the cells. For hydrophobic compounds that partition passively into the cytoplasmic membrane, a partition coefficient between an organic solvent and water, P, is one factor that could be used to predict the molecule's ability to diffuse into biomembranes. We synthesized several porphyrins, modified with two, three or four meso-substituents and studied their spectroscopic and photophysical properties. The octanol-water partitioning coefficients, log P, were calculated as a parameter for hydrophobicity. We found these porphyrins to be very hydrophobic, with log P values in the range of 8.9-11.8. These were correlated with the binding constants of these porphyrins into liposomes, K(b), as well as to their uptake by cells. The correlation between the estimated log P and K(b) is nearly linear but negative, indicating, apparently, that there is lesser binding to liposomes with increased hydrophobicity. On the other hand, all of the studied porphyrins are taken up by cells, but there is no clear correlation between cellular uptake and the log P or K(b). Lipinski's pharmacological "rule of 5" predicts poor permeation of drugs into cells when log P is greater than five. This may be relevant for diffusional binding to liposomes, where aqueous aggregation can interfere strongly with cellular uptake. In such extreme conditions, neither liposome binding nor other rules seem to predict porphyrin behavior in vitro.     

Novel pi-complexes of divalent silicon: mixed substituted neutral sandwich compounds and the half-sandwich cation (iPr5C5)Si+

The pentamethylcyclopentadienylsilicon(II) cation, Me5C5Si+, opens up access to novel silicocene derivatives; the penta-iso-propylcyclopentadienylsilicon(II) cation, iPr5C5Si+, is obtained by reaction of the mixed silicocene (iPr5C5)(Me5C5)Si with H(OEt2)2+ Al[OC(CF3)3]4-.