BACKGROUND: It is controversial whether cerebral deficits other than frank stroke develop after total aortic arch replacement using hypothermic circulatory arrest (HCA) with antegrade selective cerebral perfusion (SCP). OBJECTIVES: We investigated neuropsychological functions in patients who received total aortic arch replacement using deep HCA with SCP. METHODS: Eleven patients who underwent elective total arch replacement using deep HCA with antegrade SCP were included. Cognitive functions of the patients were evaluated at baseline, and 3 weeks and 6 months after the aortic arch surgery. RESULTS: The performance of cognitive tests did not change 3 weeks after surgery, except for the attention/calculation task of the Mini-Mental State Examination (MMSE). Six months after surgery, the decline in score for the attention/calculation task in the MMSE had reversed and the score for this task as well as for all other tests had returned to baseline levels. CONCLUSION: Long-lasting cognitive deficits other than frank stroke may not develop after total arch replacement surgery using deep HCA with SCP.

Retroviral replicating vectors (RRVs) are a nonlytic alternative to oncolytic replicating viruses as anticancer agents, being selective both for dividing cells and for cells that have defects in innate immunity and interferon responsiveness. Tumor cells fit both these descriptions. Previous publications have described a prototype based on an amphotropic murine leukemia virus (MLV), encoding yeast cytosine deaminase (CD) that converts the prodrug 5-fluorocytosine (5-FC) to the potent anticancer drug, 5-fluorouracil (5-FU) in an infected tumor. We report here the selection of one lead clinical candidate based on a general design goal to optimize the genetic stability of the virus and the CD activity produced by the delivered transgene. Vectors were tested for titer, genetic stability, CD protein and enzyme activity, ability to confer susceptibility to 5-FC, and preliminary in vivo antitumor activity and stability. One vector, Toca 511,(aka T5.0002) encoding an optimized CD, shows a threefold increased specific activity in infected cells over infection with the prototype RRV and shows markedly higher genetic stability. Animal testing demonstrated that Toca 511 replicates stably in human tumor xenografts and, after 5-FC administration, causes complete regression of such xenografts. Toca 511 (vocimagene amiretrorepvec) has been taken forward to preclinical and clinical trials.

A group of rhenium (I) complexes including in their structure ligands such as CF(3) SO(3)-, CH(3) CO(2)-, CO, 2,2'-bipyridine, dipyridil[3,2-a:2'3'-c]phenazine, naphthalene-2-carboxylate, anthracene-9-carboxylate, pyrene-1-carboxylate and 1,10-phenanthroline have been studied for the first time by mass spectrometry. The probe electrospray ionization (PESI) is a technique based on electrospray ionization (ESI) that generates electrospray from the tip of a solid metal needle. In this work, mass spectra for organometallic complexes obtained by PESI were compared with those obtained by classical ESI and high flow rate electrospray ionization assisted by corona discharge (HF-ESI-CD), an ideal method to avoid decomposition of the complexes and to induce their oxidation to yield intact molecular cation radicals in gas state [M](+.) and to produce their reduction yielding the gas species [M](-.). It was found that both techniques showed in general the intact molecular ions of the organometallics studied and provided additional structure characteristic diagnostic fragments. As the rhenium complexes studied in the present work showed strong absorption in the UV-visible region, particularly at 355 nm, laser desorption ionization (LDI) mass spectrometry experiments could be conducted. Although intact molecular ions could be detected in a few cases, LDI mass spectra showed diagnostic fragments for characterization of the complexes structure. Furthermore, matrix-assisted laser desorption ionization (MALDI) mass spectra were obtained. Nor-harmane, a compound with basic character, was used as matrix, and the intact molecular ions were detected in two examples, in negative ion mode as the [M](-.) species. Results obtained with 2-[(2E)-3-(4-tert-buthylphenyl)-2-methylprop-2-enylidene] malononitrile (DCTB) as matrix are also described. LDI experiments provided more information about the rhenium complex structures than did the MALDI ones. Copyright © 2012 John Wiley & Sons, Ltd.

The present study investigated facilitation of corticospinal excitability during motor imagery of wrist movement with visual or quantitative inspection of background electromyographic (EMG) activity. Ten healthy participants imagined wrist extension from a first-person perspective in response to a start cue. Transcranial magnetic stimulation was delivered to the motor cortex 2 sec. after the start cue. EMG signals were recorded from the extensor carpi radialis muscle. Trials with background EMG activity were discarded based on visual inspection. Both motor-evoked potential (MEP) and background EMG amplitudes increased during motor imagery. The amount of increase in MEP amplitude was positively correlated with the amount of increase in background EMG amplitude during motor imagery. The statistically significant increase in MEP amplitude during motor imagery disappeared when the effect of muscle activity was statistically eliminated or after trials with background EMG activity were discarded based on strict quantitative criteria. Facilitation of corticospinal excitability during motor imagery of wrist movement depends partially on muscle activity. Discarding background EMG activity during motor imagery based on visual inspection is not sufficient to equalize background EMG amplitude between resting and motor imagery. Discarding trials with background EMG activity through strict quantitative criteria is useful to equalize background EMG amplitude between at rest and during motor imagery.

RATIONALE Current large cluster sources such as C(60) or argon utilize gas-phase sources which are of low-brightness and cannot be focused efficiently to better than 1 micron diameter spot size. The development of a high-brightness large cluster ion source is of critical importance to achieve high resolution in secondary ion mass spectrometry (SIMS) imaging of organics. METHODS We propose a new high-brightness large cluster ion source, and a technique for producing a stable electrospray of volatile liquids under vacuum. It is known that vacuum electrospray of volatile liquids such as water is extremely difficult because of freezing of the liquids introduced in vacuum by evaporative cooling. To avoid freezing, the tip of the electrospray emitter was irradiated by a continuous wave infrared laser. RESULTS Without continuous laser irradiation the vacuum electrospray of a water/methanol solution was unstable with respect to the shapes of the Taylor cone and current, whereas continuous laser irradiation produced a stable electrospray of water. The typical modes of electrospray were clearly observed with an optical microscope even under vacuum conditions. A stable vacuum electrospray could be achieved by improving the vacuum pressure to suppress electric discharge and by using the laser to maintain the liquid state. CONCLUSIONS This is the first description of the production of a stable vacuum electrospray of volatile liquids such as water. This vacuum electrospray technique can be expected to produce a novel high-brightness large cluster ion beam source. Copyright © 2012 John Wiley & Sons, Ltd.

Covalent bonds are often created by a reaction between chemicals and protein before causing various adverse effects in a cell. Dimethylaminoethyl methacrylate (DMAEMA), which has moderate toxicity, causes skin inflammation and throat irritation. For this study, we investigated a reaction mechanism between myoglobin and (DMAEMA) using a new analytical tool developed at our laboratory: laser spray mass spectrometry technique. It was found that initially DMAEMA was added to the amino group of protein by the Michael addition mechanism; the added DMAEMA was hydrolyzed to methacrylic acid using an autocatalytic system. The results of this study indicate the feasibility of the laser spray technique in analyses of reaction dynamics. Copyright © 2012 John Wiley & Sons, Ltd.

Although there are a lot of well established methods for monitoring enzyme-catalyzed reactions, most of them are based on changes in spectroscopic properties during the conversion of substrates to products. However, reactions without optical changes are common, which are inapplicable to these spectroscopic methods. As an alternative technique for enzymologic research, mass spectrometry (MS) is favored due to its specificity, sensitivity, and the ability to obtain stoichiometric information. In this work, probe electrospray ionization (PESI) source coupled with a time of flight mass spectrometer was employed to monitor some typical protease-catalyzed reactions, including pepsinolysis and trypsinolysis of cytochrome c in real time. Due to the high electrical conductivity of each reaction system, corona discharges are likely to occur, which would decrease intensities of mass spectrometric signals. An ultra-fine sampling probe and an auxiliary vapor spray were adopted to prevent corona discharges. Experimental results from peptic and tryptic digestions of cytochrome c showed different and characteristic catalytic pathways. With the data presented in this study, PESI-MS can be considered as a potential tool for real-time monitoring of enzymatic reactions because of its simplicity in instrumental configuration, wide applicability under harsh conditions, and flexibility in combination with other techniques.

OBJECTIVES: The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH). MATERIALS AND METHODS: Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease (AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. RESULTS: The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. CONCLUSION: The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH.

AIM The aim of the present study was to carry out a retrospective survey at the Stomatology Clinic of a federal university in Brazil of 411 dental charts for the assessment of vascular tumors. METHODS After the determination of the sample, the following clinical patient information was recorded: gender, age, ethnic background, marital status, profession, place of birth, clinical diagnosis, anatomic site and tumor size. RESULTS Among all patients treated, 4.4% had benign vascular tumors in the oral cavity. The majority of these tumors were asymptomatic, with a purplish, bluish or reddish coloration and of variable size. A clinical examination and vitropressure were essential to the diagnosis. The most affected age group was 60 to 75 years. Vascular tumors most often affected white individuals and the female gender. The most common anatomic site was the tongue, followed by the buccal mucosa. Treatment with sclerotherapy proved effective, with complete regression in 94.5% of the tumors. CONCLUSION The majority of patients demonstrated wholehearted acceptance of the treatment and side effects following the administration of the substance were slight. Sclerotherapy is a simple, low-cost method of safe and easy execution, allowing the elimination of surgical trauma and a lesser risk of hemorrhage.

As the interest in gene therapy increases, the development of an efficient and reliable means to monitor gene delivery and expression in patients is becoming more important. An ideal imaging modality would be non-invasive, allowing for repeated imaging, thus validating stages subsequent to vector administration and allowing for the improvement of clinical protocols. Positron Emission Tomography (PET) has been employed for some time in clinical imaging and has in more recent years been adapted to enable imaging in small animal models, including gene therapy models for a range of diseases. PET imaging is based on the detection of trace quantities of positron-emitting molecular probe within cells postadministration, permitting imaging of target molecules in vivo, and numerous tracers have been developed for a wide range of applications, including imaging of reporter gene activity. Use of radiolabelled substrates that interact with specific transgene proteins, has identified a number of reporter genes that are suitable for imaging vector mediated gene delivery and expression in both pre-clinical and clinical situations. These reporter genes enable non-invasive analysis of the location, level and kinetics of transgene activity. Among the various imaging modalities in existence, the PET approach displays arguably the optimum characteristics in terms of sensitivity and quantitation for in vivo gene expression measurements. Given the existing availability of PET scanning equipment and expertise in hospitals, this imaging modality represents the most clinically applicable means of analysing gene therapy in patients. This review outlines the principles of PET imaging in the context of gene and cell therapy at both pre-clinical and clinical levels, comparing PET with other relevant modalities, and describes the progress to date in this field.