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Background Some research suggests that higher levels of depression and anxiety-related symptoms at intake are associated with premature termination from psychotherapy, but findings are mixed. However, theoretical and measurement considerations – introduced by a common mood factor – might complicate literature synthesis. Tellegen (1985) demonstrated that demoralization causes multicollinearity between measures of depression and anxiety, and other lines of research have converged to indicate that this construct is an important non-specific factor to consider when assessing mood pathology. Methods We utilized a sample of 557 community mental health center outpatients (188 males, 265 females; 80% Caucasian) with an average age of 32.2 years (SD=10.2). We used self-report indicators to model latent low positive emotionality and negative emotionality constructs, which are temperament markers of core depressive and anxiety symptoms. We further specified a latent demoralization bifactor from these indicators. Results As hypothesized, the bifactor model yielded significantly better fit than competing one-factor and two-factor models. Furthermore, the bifactor was substantially correlated with a demoralization measure (r=.96). As expected, low positive emotionality and negative emotionality were significant predictors of therapist ratings of premature termination. Though demoralization was a non-significant predictor, the structural paths from the other two internalizing constructs markedly increased in the bifactor model relative to the two-factor model. Limitations Replications with other, more diverse clinical populations using multi-method indicators of premature termination are needed. Conclusions This research indicates that after accounting for demoralization patients presenting with core mood disorder symptoms are at substantially increased risk for premature termination.

Previous studies suggest that presurgical psychopathology accounts for some of the variance in suboptimal weight loss outcomes among Roux-en-Y gastric bypass (RYGB) patients, but research has been equivocal.The present study seeks to extend the past literature by examining associations between presurgical scale scores on the broadband Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) and suboptimal weight loss and poor adherence to follow-up 1 year postoperatively after accounting for several methodologic considerations.Cleveland Clinic Bariatric and Metabolic Institute, Cleveland, Ohio, USA.The sample consisted of 498 RYGB patients, who produced a valid presurgical MMPI-2-RF protocol at program intake. The sample was primarily female (72.9%), Caucasian (64.9%), and middle-aged (mean = 46.4 years old; standard deviation [SD] = 11.6). The mean presurgical body mass index (BMI) was 47.4 kg/m(2) (SD = 8.2) and mean percent weight loss (%WL) at 1 year postoperatively was 31.18 %WL (SD = 8.44).As expected, scales from the Behavioral/Externalizing Dysfunction (BXD) domain of the MMPI-2-RF were associated with worse weight loss outcomes and poor adherence to follow-up, particularly after accounting for range restriction due to underreporting. Individuals producing elevated scores on these scales were at greater risk for achieving suboptimal weight loss (50% excess weight loss) and not following up with their appointment compared with those who scored below cut-offs.Patients who are more likely to engage in undercontrolled behavior (e.g., poor impulse control), as indicated by presurgical MMPI-2-RF findings, are at greater risk for suboptimal weight loss and poor adherence to follow-up following RYGB. Objective psychological assessments should also be conducted postoperatively to ensure that intervention is administered in a timely manner. Future research in the area of presurgical psychological screening should consider the impact of underreporting and other discussed methodologic issues in predictive analyses.

Although exercise stress echocardiography (ESE) is a well-validated technique in adult population, its use in children is quite limited. We aimed to assess the feasibility, the safety and the reproducibility of ESE, using on-line scanning in semi-supine cyclo-ergometer protocol in a large pediatric population. Between July 2008 and January 2013, 42 patients (mean age 14 ± 3) were evaluated with a bicycle ESE performing 50 studies. ESE was successfully performed and well tolerated by all patients. None of the patients presented with adverse effects of stress-induced ischemia. HR was 82 ± 13 at rest, and 153 ± 19.1 during peak exercise. Among 544 views analyzed for grading of image quality, the visualization was optimal in 473 (87 %), suboptimal in 39, and inadequate in 32 (6 %). 37 tests were performed in patients with congenital or acquired coronary abnormality. Regional wall motion abnormalities (RWMA) were revealed in nine cases (24 %). The agreement between the two different observers showed a K index of 0.7276 (95 % CI 0.6497–0.8055) for the image quality and a K index of 0.5125 (95 % CI 0.4782–0.5468) for the RWMA analysis. Among ten patients with hypertrophic cardiomyopathy, we were able to demonstrate the new comparison of significant left ventricular outflow tract gradient (≥30 mmHg) during exercise in three patients (30 %). Bicycle stress echocardiography performed by on-line scanning during exercise is a feasible, safe, and reproducible modality in children. Further data to assess its diagnostic accuracy are, however, needed. Stress echocardiography provides a dynamic assessment of the myocardial structure and function under conditions of physiologic or pharmacologic stress.

Recent electrophysiological studies in our laboratory have demonstrated a physiological interaction between 5-HT(2A) and metabotropic glutamate2/3 (mGlu2/3) receptors in the medial prefrontal cortex. Several behavioral studies have found that phenethylamine hallucinogens with partial agonist activity at 5-HT(2A) receptors induce head shakes when directly administered into the medial prefrontal cortex. The purpose of the present experiments was to examine whether an interaction occurs between mGlu2/3 and 5-HT(2A) receptors on a behavioral level using head shakes induced by phenethylamine hallucinogens as a model of 5-HT(2A) receptor activation. Administration of the mGlu2/3 agonist LY354740 (0.3-10 mg/kg, ip) suppressed head shakes induced by the phenethylamine hallucinogen 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Conversely, administration of the mGlu2/3 antagonist LY341495 (1 mg/kg, ip) enhanced the frequency of DOI-induced head shakes. Taken together, these results raise the possibility that the psychomimetic properties of hallucinogenic drugs may be mediated in part, via increased glutamate release following activation of 5-HT(2A) receptors.

We investigated the effects of stepwise thermal treatment of [100]-CZ- and FZ-silicon on the crystal defects and the etching behavior in KOH solutions. The anisotropy (the quotient of the vertical etch rate and the underetching of the mask), formed crystal defects as well as the surface roughness of the exposed {100}- and {111}-planes are examined. Thermal treatment of the silicon substrate can result in a precipitation of the interstitial oxygen. The precipitated oxygen causes elastic stress in the crystal which can be relieved by a generation of defects [1] , [2] . We found out that the evolution of these defects accelerates the lateral etch rate considerably. For the reference, the samples without thermal treatment the anisotropy has a value of 120 for FZ-silicon and 70 for CZ-silicon, respectively. However, with rising temperature and process time the anisotropy decreases to 30 for FZ-silicon and 15 for CZ-silicon. At the same time, the surface quality of the {100}- and {111}-planes degrades with increasing temperature. The roughness value Ra rises from 5 nm to approximately 30 nm. Along with the variation of the etching behavior during thermal treatment, we further present a suitable model for the oxygen-dependence of the etch rate.

Integrated petrological and geochemical examination of metasedimentary assemblages associated with mesothermal lode gold mineralization in five major centers of past and present production (Ballarat, Percydale, Tarnagulla, Maldon, Fosterville) in central Victoria, Australia, reveal that hydrothermal alteration in the hosting Cambro-Ordovician turbidites is much more pronounced and extensive than has previously been recognized. Characteristically, the auriferous reef structures are surrounded by bleached zones up to several tens of meters wide. Sericitization, carbonatization and carbonate spotting, and pyrite and arsenopyrite porphyroblasts—within and beyond zones of visible bleaching—are the most obvious features of alteration. Quantitative XRD analysis illustrates that these marked bleached halos are due to the replacement of albitized plagioclase clasts by white mica and the breakdown of metamorphic chlorite to form secondary carbonates, and to a lesser extent, kaolin. The negative correlation between metamorphic chlorite and hydrothermal carbonate phases provides a reliable mineralogical alteration index useful to exploration. Geochemical reconnaissance profiles also indicate the development of systematic trends in response to hydrothermal alteration involving mainly SiO2, K2O, Na2O, CO2, As, Au, and S at constant bulk rock volume. Calculation of a geochemical alteration index given by the ratio K2O + CO2 / K2O + CO2 + Na2O + Al2O3 suggests that this can be a reliable indicator of alteration, in particular where concentrations of individual invariable oxides such as Al2O3 vary too much in response to lithological variations. Saturation indices that are based on ratios of 3K/Al and CO2/(Mg + Fe + Ca) are less reliable, because muscovite and carbonate are not always the dominant alteration mineral species of relevance. The alteration assemblages, as well as mineralogical and geochemical trends at the five ore systems investigated herein, are common to many slate belt-hosted gold deposits. The results of this investigation show that, although the detection of such systematic spatial variations relative to mineralization can be complicated, for example by postore modification of the wall rocks due to contact metamorphism (e.g., at Maldon) or where mineralization is not associated with massive to laminated quartz veins (e.g., at Fosterville), recognition of extensive, though not always conspicuous, alteration halos around mesothermal lode gold mineralization represents a potentially powerful tool for exploration in slate belts.

The serotonin (5-HT) hypothesis of schizophrenia arose from early studies on interactions between the hallucinogenic drug LSD (D-lysergic acid diethylamide) and 5-HT in peripheral systems. More recent studies have shown that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and phenethylamines (e.g. , mescaline), produce their central effects through a common action upon 5-HT(2) receptors. This review focuses on two brain regions, the locus coeruleus and the cerebral cortex, where the actions of indoleamine and the phenethylamine hallucinogens have been shown to be mediated by 5-HT(2A) receptors; in each case, the hallucinogens (via 5-HT(2A) receptors) have been found to enhance glutamatergic transmission. In the prefrontal cortex, 5-HT(2A)-receptors stimulation increases the release of glutamate, as indicated by a marked increase in the frequency of excitatory postsynaptic potentials/currents (EPSPs/EPSCs) in the apical dendritic region of layer V pyramidal cells; this effect is blocked by inhibitory group II/III metabotropic glutamate agonists acting presynaptically and by an AMPA/kainate glutamate antagonist, acting postsynaptically at non-NMDA glutamate receptors. A major alternative drug model of schizophrenia, previously believed to be entirely distinct from that of the psychedelic hallucinogens, is based on the psychotomimetic properties of antagonists of the NMDA subtype of glutamate receptor (e.g., phencylidine and ketamine). However, recently it has been found that many of the effects of the NMDA antagonists may also (1) involve 5-HT(2A) receptors and (2) be mediated through excess activity at non-NMDA (i.e., AMPA/kainate) glutamate receptors. Moreover, pharmacological manipulations of glutamate transmission (e. g., by inhibitory metabotropic glutamate agonists) provide unexpected parallels between the actions of these two classes of drugs. Given an emerging recognition of the importance of alterations in glutamatergic transmission in the actions of both psychedelic hallucinogens an NMDA antagonists, this review concludes with of implications for the pathophysiology and therapy of schizophrenia.

A prototype of a solid deuterium (SD 2 ) source of Ultra-Cold Neutrons (UCN) is currently being tested at LANSCE. The source is contained within an assembly consisting of a 4 K polyethylene moderator surrounded by a 77 K beryllium flux trap in which is embedded a spallation target. Time-of-flight measurements have been made of the cold neutron spectrum emerging directly from the flux trap assembly. A comparison is presented of these measurements with results of Monte Carlo (LAHET/MCNP) calculations of the cold neutron fluxes produced in the prototype assembly by a beam of 800 MeV protons incident on the tungsten target. A UCN detector was coupled to the assembly through a guide system with a critical velocity of 8 m/s ( 58 Ni). The rates and time-of-flight data from this detector are compared with calculated values. Measurements of UCN production as a function of SD 2 volume (thickness) are compared with predicted values. The dependence of UCN production on SD 2 temperature and proton beam intensity are also presented.

The dynamic behaviour of biofilters intended to remove toluene and xylene from air was studied during transient states. Laboratory scale biofilters were filled with a mixture of peat, bark and wood and inoculated with a mixed microbial population. Toluene and xylene were applied both as single pollutants and as mixtures. Attention was focused on the evaluation of the following transients: the response of biofilters to step changes and peaks in pollutant concentrations, the effect of changes between single and multiple pollutant loadings and the response to shutdown periods. The biofilters demonstrated a good dynamic stability during transient states induced by change in inlet pollutant concentrations. Their time periods did not exceed three hours. No interaction between xylene and toluene degradation was observed during changes in loading with single pollutants or their mixture. The performance interruptions lasting less than 24 hours were found to have no significant influence on the removal efficiency of biofilters. When the biofilters were reacclimated after longer starvation periods, a short temporary decrease in efficiency whose minimum and duration were proportional to the length of a preceding shutdown period was observed. The longest starvation period (7 days) resulted in a reacclimation lasting 7 hours only. Adaptations of a microbial population to new operating conditions as well as sorption/desorption processes were suggested as the main factors influencing the dynamic reponse characteristics.

Interest in the role of serotonin (5-HT) in the therapeutic effects of atypical antipsychotic drugs originated from the observations that: (1) clozapine and other atypical drugs have a high affinity for 5-HT2A relative to D2 receptors; and (2) 5-HT2A receptors mediate the central effects of psychedelic hallucinogens. Recently, we found that 5-HT evokes a focal release of glutamate in the apical dendritic field of layer V pyramidal cells in prefrontal cortex, measured electrophysiologically by an increased frequency of spontaneous excitatory postsynaptic potentials/currents (EPSPs/EPSCs). An atypical mode of transmitter release (termed asynchronous release) seems to be involved because EPSC induction is tetrodotoxin (TTX)-sensitive but is not dependent on impulse flow and is supported by Sr2+ in the absence of external Ca2+. The 5-HT-induced increase in spontaneous EPSCs is blocked completely by the selective 5-HT2A antagonist M100907 (MDL 100,907). M100907 also blocks the enhancement by hallucinogens of a late, asynchronous component of electrically evoked EPSPs/EPSCs. Group II/III metabotropic glutamate agonists, which act downstream from 5-HT2A receptors at presynaptic inhibitory autoreceptors, markedly suppress the 5-HT-induced release of glutamate. Subtype-selective group II/III agonists, such as the group II metabotropic agonist LY354740, are particularly interesting in terms of therapeutic potential, because they are able to suppress the 5-HT2A-induced EPSCs while sparing overall glutamatergic transmission. An analysis of the mechanisms by which 5-HT2A receptors induce glutamate release suggests new targets for the design of novel treatments for schizophrenia.

We describe the design and expected performance of the PHENIX Multiplicity and Vertex Detector (MVD) sub-system of the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC).

The PHENIX Multiplicity Vertex Detector (MVD) provides event characterization, a centrality trigger, collision vertex position, and measures fluctuations in charged particle multiplicities. The design criteria include a large rapidity coverage, good azimuthal coverage and granularity, minimizing material in the electron arm acceptance, and minimizing costs. The MVD contains two concentric barrels of Si strip detectors with two disk-shaped Si pad detector endcaps. Simulations show that the vertex position can be located to within a few hundred microns using hits in the barrels. A channel multiplicity signal is formed for use in the Level-1 trigger. The effect of the expected discriminator performance on this trigger signal will be shown. The pad and strip detectors are read-out with identical electronics. The influence of the performance of the electronics on the detector's performance are discussed.

Residual macrostresses are measured on samples having a surface layer composed of a steel substrate and a thin TiN coating. The surface of machine components can be covered by a TiN layer for the purpose of increasing hardness and wear resistance. Various methods are used for the deposition of this layer. Among them there are: physical vapour deposition (PVD), like-ion plating, sputter ion plating, magnetron sputtering (MS), and chemical vapour deposition. This article deals with the layers of TiN deposited on steel 12050 using PVD-MS. The TiN layer is studied in connection with residual stress distribution and the machining of the substrate surface. The substrate is machined by milling and then coated with a TiN layer.

This brief review traces the serotonin (5-HT) hypothesis of the action of hallucinogenic drugs from the early 1950s to the present day. There is now converging evidence from biochemical, electrophysiological, and behavioral studies that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and the phenethylamines (e.g., mescaline), have a common site of action as partial agonists at 5-HT2A and other 5-HT2 receptors in the central nervous system. The noradrenergic locus coeruleus and the cerebral cortex are among the regions where hallucinogens have prominent effects through their actions upon a 5-HT2A receptors. Recently, we have observed a novel effect of hallucinogens--a 5-HT2A receptor-mediated enhancement of nonsynchronous, late components of glutamatergic excitatory postsynaptic potentials at apical dendrites of layer V cortical pyramidal cells. We propose that an effect of hallucinogens upon glutamatergic transmission in the cerebral cortex may be responsible for the higher-level cognitive, perceptual, and affective distortions produced by these drugs.

Previously, serotonin (5-HT) was found to induce a marked increase in glutamatergic spontaneous excitatory postsynaptic currents (EPSCs) in apical dendrites of layer V pyramidal cells of prefrontal cortex; this effect was mediated by 5-HT2A receptors, a proposed site of action of hallucinogenic and atypical antipsychotic drugs. Unexpectedly, although the effect of 5-HT was Ca2+-dependent and tetrodotoxin-sensitive, it did not appear to involve the activation of excitatory afferent impulse flow. This paradox prompted us to investigate (in rat brain slices) whether 5-HT was acting through an atypical mode of excitatory transmitter release. We found that the frequency of 5-HT-induced spontaneous EPSCs was fully supported by Sr2+ in the absence of added Ca2+, implicating the mechanism of asynchronous transmitter release which has been linked to the high-affinity Ca2+-sensor synaptotagmin III. Although the early, synchronous component of electrically evoked EPSCs was reduced while 5-HT was being applied, late, nonsynchronous components were enhanced during 5-HT washout and also by the 5-HT2 partial agonist 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI); the effect of DOI was blocked by a selective 5-HT2A antagonist (MDL 100,907). This late, nonsynchronous component was distinct from conventional polysynaptic EPSCs evoked in the presence of the GABAA antagonist bicuculline, but resembled asynchronous glutamatergic excitatory postsynaptic potentials (EPSPs) evoked in the presence of Sr2+. An enhancement of asynchronous EPSCs by a specific neurotransmitter receptor has not been reported previously. The possible role of excessive asynchronous transmission in the cerebral cortex in mediating the hallucinogenic effects of 5-HT2A agonists such as DOI is discussed.

We compared 5-hydroxytryptamine (5-HT), norepinephrine and dopamine for their efficacy at increasing excitatory postsynaptic current frequency in layer V pyramidal cells from rat medial prefrontal cortical slices. 5-HT, norepinephrine and dopamine increased the excitatory postsynaptic current frequency by 15.9-, 4.5- and 1.7-fold, respectively. Similar to previous results with 5-HT-induced excitatory postsynaptic currents, blockade of mu-opioid receptors, of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors and fast Na+ channels suppressed the norepinephrine-induced excitatory postsynaptic currents. The norepinephrine-induced, and in most cases, the dopamine-induced increase in excitatory postsynaptic current frequency was blocked by the alpha1-adrenoceptor antagonist prazosin while the alpha2-adrenoceptor antagonist yohimbine did not block either the norepinephrine- or the 5-HT-induced increase in excitatory postsynaptic currents frequency. The potency of three 5-HT2 receptor antagonists with varying selectivity for 5-HT2A/2B/2C receptors tested against the 5-HT-induced increase in excitatory postsynaptic current frequency are in agreement with the affinity of these drugs for the 5-HT2A receptor. These findings suggest that 5-HT2A receptor or alpha1-adrenoceptor activation enhance neurotransmitter release from a similar subset of glutamate terminals that innervate apical dendrites of layer V pyramidal cells.

A short description of a new accelerator called KALIF–HELIA is given, that is presently under construction at the Forschungszentrum Karlsruhe. This High Energy Linear Induction Accelerator couples a self-magnetically insulated transmission line with the induction linac technology: the 1 MV pulses from 6 induction cells are added in a “magnetically insulated voltage adder” (MIVA) delivering for 50 ns a pulse of 6 MV and 400 kA to a matched load. This technology is considered in all light ion beam driven reactor concepts as a low cost alternative for the production of energy by inertial fusion (IFE). The pulses delivered by these generators are coupled to diodes that generate the intense light ion beams. Focusing of these beams is presently insufficient and requires scaling to IFE conditions. However, the available scaling laws for beam divergence are not in agreement with the few results from experiments performed at high power levels. Therefore, a verification and improvement of these scaling laws is necessary in order to extrapolate more reliably to beams needed for IFE conditions. For the start-up phase – foreseen for end 1997 – KALIF–HELIA will be operated first in negative polarity generating an electron beam. The subsequent operation of the accelerator in positive polarity will allow the verification of the voltage dependence in the divergence scaling laws for proton beams and acceleration voltages up to 6 MV. In a second step, the predicted influence of the ion mass on the beam divergence will be investigated by accelerating Li+ ions instead of protons.

Neurological disease both results from and produces imbalances in the functions of brain circuitry, with resultant alterations in behavior, cognition, and social interactions, among others aspects. These issues can contribute heightened risk for suicidal behavior under a diathesis consistent with such behavior. In this chapter, risk for suicide is addressed for a number of neurological disorders, including Autism Spectrum Disorder (ASD), Parkinson’s Disease, epilepsy, and Tourette’s Disorder. Neurologic disease is very frequently comorbid with psychiatric disease, although it can be difficult to separate symptoms of the primary neurological disorder from what might be an independent psychiatric disorder. However, given the high incidence of psychiatric symptoms in neurological disorders, especially anxiety and depression, some of these patient populations can be at especially high risk, and should be carefully monitored as a result.

A Multiplicity-Vertex Detector (MVD) has been designed, and is in construction for the PHENIX Experiment at the Relativistic Heavy Ion Collider (RHIC). The 35 000 channel silicon detector is a two-layer barrel comprised of 112 strip detectors, and two disk-shaped endcaps comprised of 24 wedge-shaped pad detectors. The support structure of the MVD is very low mass, only 0.4% of a radiation length in the central barrel. The detector front-end electronics are a custom CMOS chip set containing preamplifier, discriminator, analog memory unit, and analog-to-digital converter. The system has pipelined acquisition, performs in simultaneous read/write mode, and is clocked by the 10 MHz beam crossing rate at RHIC. These die, together with a pair of commercial FPGAs that are used for control logic, are packaged in a mutlichip-module (MCM). The MCM will be fabricated in the High-Density-Interconnect (HDI) process. The prototype MCM design layout is described.

By intracellular and whole cell recording in rat brain slices, it was found that bath-applied serotonin (5-HT) produces an increase in the frequency and amplitude of spontaneous excitatory postsynaptic potentials/currents (EPSPs/EPSCs) in layer V pyramidal cells of neocortex and transitional cortex (e.g. medial prefrontal, cigulate and frontoparietal). The EPSCs were suppressed by LY293558, an antagonist selective for the AMPA subtype of excitatory amino acid receptor, and by two selective 5-HT2A receptor antagonists, MDL 100907 and SR 46349B. In addition, the EPSCs were suppressed by the fast sodium channel blocker tetrodotoxin (TTX) and were dependent upon external calcium. However, despite being TTX-sensitive and calcium dependent, there was no evidence that the EPSPs resulted from an increase in impulse flow in excitatory neuronal afferents to layer V pyramidal cells. The EPSCs could be induced rapidly by the microiontophoresis of 5-HT directly to "hot spots" within the apical (but not basilar) dendritic field of recorded neurons, indicating that excitatory amino acids may be released by a TTX-sensitive focal action of 5-HT on a subset of glutamatergic terminals in this region. Consistent with such a presynaptic action, the inhibitory metabotropic glutamate receptor agonist (1S,3S)-aminocyclopentane-1,3-dicarboxylate markedly reduced the induction of EPSPs by 5-HT. Postsynaptically, 5-HT enhanced a subthreshold TTX-sensitive sodium current, potentially contributing to an amplification of EPSC amplitudes. These data suggest 5-HT. via 5-HT2A receptors, enhances spontaneous EPSPs/EPSCs in neocortical layer V pyramidal cells through a TTX-sensitive focal action in the apical dendritic field which may involve both pre- and postsynaptic mechanisms.

Conditions are described for the preparation of 188Re-RC-160, a radiolabeled synthetic peptide derived from an analogue of somatostatin, using a lyophilized labeling kit containing RC-160 (200 μg) and stannous tartrate to which is added carrier-free 188 Re (β, E max , 2,12 MeV ; γ, 155 KeV , 10%, T 1 2 = 16.7 h ) . The 3its have been radiolabeled with > 2960 Mbq (80 mCi) with a high labeling efficiency and no need for subsequent purification. Radiolabeling results in one major peak when analyzed by reverse-phase (RP) HPLC. Presumptive radiolysis was detected at 2.5 h post-labeling; however, a convenient method is described for stabilizing the kits against radiolysis by the post-labeling addition of ascorbic acid.

The prevention of an inflammation in the brain is one of the most important goals the body has to achieve. As pericytes are located on the abluminal side of the capillaries in the brain, their role in fighting against invading pathogens has been investigated in some points, mostly in their ability to behave like macrophages. Here we studied the potential of pericytes to react as immune cells under inflammatory conditions, especially regarding the expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), major histocompatibility complex II (MHC II) molecules, CD68, as well as the generation of reactive oxygen and nitrogen species (RONS), and their ability in phagocytosis. Quantitative real time PCR and western blot analysis showed that pericytes are able to increase the expression of typical inflammatory marker proteins after the stimulation with tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), interferon-gamma (IFN-gamma), or lipopolysaccharides (LPS). Depending on the different specific pro-inflammatory factors pericytes changed the expression of alpha smooth muscle actin (alpha SMA), the most predominant pericyte marker. We conclude that the role of the pericytes within the immune system is regulated and fine-tuned by different cytokines strongly depending on the time when the cytokines are released and their concentration. The present results will help to understand the pericyte mediated defense mechanisms in the brain.

ABT-384 is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1). The pharmacokinetics of ABT-384 was evaluated in healthy volunteers in single-dose (1, 8, 20, 50, 120 and 240 mg) and multiple-dose studies (1, 2, 4, 8, 20, 30 and 100 mg once daily). Less than dose-proportional pharmacokinetics of ABT-384 was observed when ABT-384 was administered at single doses lower than 8 mg. This nonlinear phenomenon disappeared after repeated doses. The dose-normalized plasma concentration-time curves superposed across all dose groups on day 7, but not on day 1. This phenomenon cannot be explained by the half-life of ABT-384. Based on available data, the nonlinearity is likely due to binding of ABT-384 to a high-affinity-low-capacity site, such that this interaction was reflected in ABT-384 pharmacokinetics. To characterize the pharmacokinetics of ABT-384, a population pharmacokinetic model for ABT-384 was constructed. The model provided reasonable fitting for both single- and multiple-dose data. Further investigation is warranted to evaluate the disposition of ABT-384 at low doses using a larger number of subjects. The constructed model would be useful in predicting ABT-384 concentrations at different doses and guiding the selection of dosing regimens in further clinical trials.

Cushing's syndrome is a rare disorder with variable aetiology which is connected with significantly increased morbidity and mortality. Therefore, early determination of correct aetiology and early treatment are essential for a decrease of morbidity and mortality of patients. Present article introduces review and current recommendation of Czech Society of Endocrinology for the treatment of Cushings syndrome.

Odland, Berthelson, Sharma, Martin, and Mittenberg ( 2013 ) caution that clinically elevated scale scores produced by members of the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008 /2011) normative sample raise concerns about the potential for false positive findings of psychopathology. However, the MMPI-2-RF normative sample is intended to represent the general population of the United States, 26.2% of which met criteria for a Diagnostic and Statistical Manual-IV (APA, 1994 ) disorder in a 12-month period (Kessler, Chiu, Demler, & Walters, 2005 ). In the current study we compare scale elevation rates in the MMPI-2-RF normative sample to prevalence rates of mental disorders primarily drawn from the National Comorbidity Study Replication (Kessler et al., 2005 ). Our objective was to evaluate MMPI-2-RF elevation rates in an epidemiological context. Results indicate that MMPI-2-RF scale elevation rates were generally consistent with epidemiological data when examined in the context of standard interpretation guidelines for the inventory. We also reiterate Ben-Porath and Tellegen's (2008/2011) caution that MMPI-2-RF scale elevations alone are not sufficient to indicate the presence of psychiatric disorder. Rather they are best viewed as indications of the need to evaluate the individual for possible disorder(s). Implications of these results, limitations of this study, and future directions in research are discussed.

There is a need for a simple, fast, efficient and sensitive method for analysis of glyphosate and its degradate aminomethylphosphonic acid (AMPA) in diverse matrices such as water, vegetation and soil.Aqueous extracts from water, vegetation and soil were passed through reverse-phase and cation-exchange columns and directly injected into a tandem mass spectrometer using only a guard column for separation. Extraction efficiencies from the three matrices were80% for both glyphosate and AMPA. The method reporting levels (MRLs) for glyphosate in water, vegetation and soil were 3.04 µg L(-1) , 0.05 mg kg(-1) and 0.37 mg kg(-1) respectively. AMPA MRLs were 5.06 µg L(-1) for water, 0.08 mg kg(-1) for vegetation and 0.61 mg kg(-1) for soil.A validated, simple and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for routine analysis of glyphosate and AMPA in water, vegetation and soil that uses minimal sample handling and clean-up will facilitate the additional environmental research needed to address the continuing concerns related to increasing glyphosate use.

In pregnancy, the volume of pituitary increases by multiplication of lactotopic and gonadotropic cells and developing placenta is the source of numerous hormones and enzymes that significantly affect and alter the function of the endocrine system. This naturally has an impact on the course of pituitary disorders and their treatment. The most common disorders of pituitary gland, which we can meet in pregnancy, are adenomas, particularly prolactinomas, and functionless adenomas. During pregnancy we avoid the treatment of microprolactinomas, but in macroprolactinomas where there is the risk of their enlargement by stimulation of placental estrogens, we administer preventively the dopaminergic agonists. Patients with acromegaly usually do not need the treatment during pregnancy, unless there is a danger to damage the visual pathway or heavy headaches occur. ACTH secreting adenomas (Cushings disease) in pregnancy are rare, they are difficult to diagnose but existing hypercortisolism is very dangerous to fetus and may damage even mother. Large functionless adenomas, unless treated before pregnancy, may damage the visual pathway. The volume of the enlarged pituitary gland in pregnancy and sometimes even of the functionless adenoma adenoma, may be reduced by cabergoline, so that the urgent neurosurgery in pregnancy is very rare. A typical disease that occurs primarily in pregnant women is autoimmune lymphocytic hypophysitis. Diagnosis is established on the basis of headaches and symptoms and signs of the deficits of adrenocorticotropic and thyreotropic function usually in the last third of pregnancy or in the first six months after birth, using a specific image in magnetic resonance. Treatment is limited to hormone replacement. It is also possible to meet pregnant women with deficient pituitary functions. In hypocortical women with exception of strains like as pregnancy vomiting, doses of hydrocortisone replacement usually do not change until birth. Childbirth, however, must be secured by increasing the doses of corticosteroids. Careful replacement of thyroid hormones in hypothyroid women is very important for the development of fetus. In women treated with growth hormone its administration during pregnancy may be omitted because the placental growth hormone takes over its function. Desmopressin dose for diabetes insipidus in pregnancy is unchanged - desmopressin is resistant to placental vasopressinases. However, their effects may cause manifestation of partial diabetes insipidus, which was compensated so far.

Studies have demonstrated that negative affect increases prior to food intake in individuals diagnosed with an eating disorder. Mindfulness has been supported empirically to treat experiential avoidance stemming from anxiety. Thus, the current objective in this study is to empirically compare mindfulness vs. thought suppression invention during a food exposure in both clinical and nonclinical samples.In a 2 (Group: clinical vs. nonclinical) × 2 (INTERVENTION: mindfulness vs. distraction) counterbalanced within treatment design, the current investigation sought to determine the differential effectiveness of a brief mindfulness intervention vs. a brief distraction intervention in women diagnosed with AN and BN in a clinical and nonclinical sample during a food exposure.Results indicated that the eating disorder group reported a significant increase in negative affect after the mindfulness intervention as compared to the distraction intervention, whereas the nonclinical group reported a significant decrease in negative affect after the mindfulness intervention as compared to the distraction intervention.Preliminary findings suggest that clinicians may want to proceed cautiously when using mindful eating in those with severe eating disorders during the early stages of food exposure. Limitations and future directions are discussed.

Background In this study we assessed increased cortisol in Alzheimer's disease (AD) patients. The selective 11-β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor ABT-384 blocked regeneration of active cortisol and this tests the hypothesis that intracellular hypercortisolism contributes to cognitive impairment. Methods In this double-blind, placebo- and active-controlled phase II study we examine the efficacy and safety of ABT-384 given 10 mg or 50 mg once daily, donepezil 10 mg once daily, or placebo for 12 weeks in subjects with mild-to-moderate AD. The primary efficacy end point was the change from baseline to final evaluation on the 13-item Alzheimer's Disease Assessment Scale–Cognitive subscale (ADAS-Cog) total score. Results The study was terminated for futility after randomization of 267 subjects. ABT-384 did not improve ADAS-Cog scores or any secondary end point; however, donepezil significantly improved both cognition and functional end points. Overall incidence of adverse events was similar among treatment groups. Conclusion ABT-384, when tested at doses associated with complete brain HSD-1 inhibition, did not produce symptomatic improvement in AD.

High-quality video-mediated communication uses data streams with high bitrates, often comparable to capacity of network links, it also demands latency to be as low as possible. The problem of finding the optimal solution to multi-point data distribution on application level while minimizing distribution latency is NP-complete. This paper presents a novel approach to solving the problem using local search methods. Experimental evaluation within the Co Universe framework shows that the proposed algorithm is capable of solving problems an order of magnitude larger than previously available approaches, while maintaining high quality of the solutions. The proposed approach also makes initial attempts toward handling of system dynamics and minimizing the impact on already participating users.

Pharmacological techniques have defined the existence of two different alpha 1-adrenoceptors, the alpha 1A- and alpha 1B-adrenoceptor subtypes and both of these receptors have been cloned in addition to a cloned alpha 1d-adrenoceptor. A subpopulation of interneurons in layer III of the rat piriform cortex that are excited by 5-hydroxytryptamine (5-HT) via 5-HT2A receptors are also excited by norepinephrine via alpha 1-adrenoceptors. In the present study we determined the pA2 values against the norepinephrine-mediated excitation of piriform cortical interneurons for a number of antagonists that are (1) not selective for alpha 1A- or alpha 1B-adrenoceptors (prazosin), (2) selective for alpha 1A-adrenoceptors (5-methyl urapidil, 2-(2,6-dimethoxy-phenoxyethyl)- aminomethyl-1,4-benzodioxane hydrochloride (WB 4101), benoxathian, phentolamine) and (3) selective for alpha 1B-adrenoceptors (spiperone and risperidone). The pA2 values for the antagonist blockade of norepinephrine-mediated interneuron excitation were significantly correlated to literature values for the pKi values of antagonist binding to the alpha 1B-adrenoceptor (r = 0.919) and the cloned alpha 1b-adrenoceptor (r = 0.849) but were not correlated to the pKi values of antagonist binding to the alpha 1A-adrenoceptor or the cloned alpha 1a- and alpha 1d-adrenoceptor. Thus, we conclude that this population of piriform cortical interneurons is excited by norepinephrine via alpha 1B-adrenoceptors.

A multiresidue method for the determination of chlorsulfuron, metsulfuron-methyl, thifensulfuron-methyl, and triasulfuron in soil by high-performance liquid chromatography/electrospray/mass spectrometry (LC/ES/MS) is reported. A clay loam soil, spiked at 6.0 μg kg-1 with all four herbicides, was extracted with 0.1 M ammonium carbonate, and the extract was cleaned up by C18-SPE. The herbicides were quantified using selected ion monitoring. The percent recoveries were as follows: chlorsulfuron, 80.1 ± 7.9%; metsulfuron-methyl, 99.4 ± 8.6%; thifensulfuron-methyl, 95.9 ± 5.9%; and triasulfuron 100.5 ± 24.3%. We have shown that we can analyze and confirm four 4-methoxy-6-methyl-1,3,5-triazin-2-yl-containing sulfonylurea herbicides in soil by LC/ES/MS. This multiresidue method should also be appropriate for other sulfonylurea and polar herbicides. Keywords: Chlorsulfuron; metsulfuron-methyl; thifensulfuron-methyl; triasulfuron; LC/MS; electrospray; soil

Monoclonal antibodies can be directly labelled with 188Re using a simple one-step radiolabelling kit. Using B72.3 as a model antibody, the formulation was optimized and kits were made and tested and compared to data previously reported for the same antibody labelled with other radioisotopes. Labelling with Re-188 was carried out with the eluate of a W-188/Re-188 generator from Oak Ridge National Laboratory. Fresh generator eluate was added to the pre-reduced lyophilized antibody and the mixture allowed to incubate overnight at room temperature. The radiochemical purity, immunoreactive fraction, and biodistribution in normal and LS174T tumor bearing nude mice was determined. The radiochemical purity was 88 ± 7%, the immunoreactive fraction was 68.46 ± 3.8%. The immunoreactive fraction was higher than any previously reported for this antibody when labelled with other radioisotopes. At 48 h, 7.9 ± 2.4% of the injected dose per gram was found in the tumor. The biodistribution and tumor uptake of Re-188 labelled B72.3 was similar to that previously reported for Re-186 and In-111 labelled B72.3.

Metabotropic glutamate 2/3 (mGlu2/3) receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL) and infralimbic (IL) cortex. LY354740 (10 and 30 mg/kg, i.p.) showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.). Because both compounds inhibit serotonin 2A receptor (5-HT2AR)-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

Important functional interactions between the metabotropic glutamate 2 (mGlu2) and 5-hydroxytryptamine2A (5-HT₂A) neurotransmitter receptors have been established based on electrophysiological, biochemical and behavioral evidence. Over the last several years, dimerization between 5-HT₂A and mGlu2 receptors has been proposed to account for the functional cross-talk between these two receptors in the prefrontal cortex. The pros and cons for the existence of a heteromeric complex between 5-HT₂A and mGlu2 receptors will be reviewed here. First, the fundamental criteria needing to establish evidence for heteromeric complexes will be reviewed. Then, the in vitro evidence for and against heteromeric complexes between 5-HT₂A and mGlu2 receptors will be discussed in regard to physical and functional interactions. Finally, the data with native in situ mGlu2 and 5-HT₂A receptors will be discussed with respect to whether heteromeric complexes or a simple functional interaction between two distinct GPCRs based on brain network activity is the more simple explanation for a range of in vivo data.

Back pain is experienced by up to of 85% of the United States population. Most often it resolves with minimal to no medical treatment. For those whose pain endures, worsens, or becomes protracted, conservative care is typically first attempted. Individuals who continue to experience significant back pain are often considered for surgical procedures, the results of which are not uniformly positive. The consequences of failed surgical intervention can be quite devastating, and psychosocial factors have been found to predict poor outcome. The literature on psychosocial risk factors for failed back surgery is reviewed first, identifying psychological dysfunction in the domains of emotions, cognitions, behavior, and interpersonal processes as increasing the risk for failed back surgery. Empirical findings with the MMPI-2 Restructured Form (MMPI-2-RF) are presented next, including descriptive analyses with a sample of 1341 individuals assessed as part of a pre-surgical psychological screening. Correlations between MMPI-2-RF scale scores and measures of the primary risk factors identified in this review are reported for a smaller sample of 197 pre-surgical candidates. Interpretive implications of the MMPI-2-RF findings are discussed along with suggestions for further research in this area.

γ-Glutamyltranspeptidase (GGT, syn. γ-Glutamyltransferase) and dipeptidylpeptidase-IV (DPP-IV) activity participates in metabolic and growth control of normal and tumor cells by processing biologically active peptides. Here, we report on up-regulation of these enzymes in human brain gliomas determined by catalytic enzyme histochemistry and immunocytochemistry. Higher activity of GGT was found in 50%, 68% and 81% of WHO grade II, III and IV tumors, respectively. The process started at/near the microvasculature, from where it spread to the parenchyma. On average, the enzyme activity in grade II, III and IV gliomas exceeded controls 2.0, 3.0 and 3.5-fold, respectively. Up-regulation of DPP-IV-like activity also started at the microvasculature, but mainly in pericytes and mononuclear-like cells around the vessels and dispersed in the parenchyma. Marked elevation of this enzyme activity, comprising also tumor parenchyma, occurred only in grade IV glioblastomas (65% patients; 3.6 times above controls) which can, therefore, help in their differentiation from grade III gliomas. The increase of total DPP-IV-like activity also included its two enzymatic homologs, the canonical DPP-IV/CD26 and FAP-1α. The increase in GGT is supposed to be a tumor grade dependent response of microvasculature and tumor astrocytes to stress induced by tissue hypoxia and/or the metabolic aberrancies. The increase in DPP-IV-like activity in high-grade tumors can be attributed to inflammatory/scavenging processes performed by the mononuclear-like cells and, in glioblastomas, also to regressive changes in the structure and function of the microvasculature and tumor parenchyma, including astrocyte stress response. The inverse relationship between DPP-IV-like activity and Ki67 in most glioblastomas and shorter survival time of patients with low activity of this enzyme also suggest its anti-oncogenic effects.

Epitaxially grown polycrystalline silicon (epi-poly) has shown great promise as a MEMS material, offering isotropic material properties with minimal residual stress and stress gradients. While epi-poly has been used previously for MEMS inertial systems or sensors, its use in high precision resonator applications has been restricted to an encapsulation layer for resonators fabricated in single crystal silicon. In this work, encapsulated resonators fabricated with epi-poly as the functional layer were tested alongside single crystal silicon devices with regard to resonant frequency, quality factor, temperature dependence, and stability. Test results indicate that epi-poly resonators have very similar mechanical properties and stability to single crystal silicon resonators when operated in a clean package.

ABT-384 is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1), the enzyme that regenerates cortisol in several tissues. Two clinical studies of ABT-384 were undertaken to assess its safety, pharmacokinetics, target engagement, and pharmacologic effects in healthy subjects. Single doses from 1 to 240 mg, and multiple doses from 1 to 100 mg once daily for 7-14 days, were administered to healthy adults. Multiple doses from 10 to 100 mg once daily for 21 days were administered to elderly subjects. A total of 103 subjects received at least 1 dose of ABT-384. A maximum-tolerated dose was not defined in either study. The pharmacokinetic profiles of ABT-384 and its active metabolite support once daily dosing. Analysis of urine cortisol metabolites demonstrated full hepatic HSD-1 inhibition with regimens from 1 mg daily, and confirmed in vitro target selectivity. Pharmacologic effects included increases of adrenocorticotrophic hormone levels, cortisol production and androgen and estradiol levels. ABT-384 has a wide therapeutic index relative to full hepatic target engagement which is relevant for indications such as diabetes and metabolic syndrome. Its therapeutic index for other potential indications such as Alzheimer's disease remains to be established.

Polycystic ovary syndrome is one of the most common endocrinopathy in women of fertile age. It is commnoly accompanied by an increased occurence of cardiovascular risk factors. This association led to a consensus statement of Androgen Excess Society for screening of cardiovascular risk factors. We present the recommendations of Czech Endocrine and Czech Diabetological Societies for the screening and primary prevention of cardiovascular diseases and diabetes mellitus.

The effects of four serotonin (5-HT)-1A compounds (buspirone, gepirone, ipsapirone and zalospirone) were compared with 5-hydroxytryptophan (5-HTP) [a 5-HT precursor with antidepressant (AD) efficacy], and diazepam (a benzodiazepine anxiolytic), on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Past research has shown that AD and anxiolytic compounds each have distinct effects on the DRL 72-s interresponse time (IRT) distribution profile. In the present paper, the profile of the IRT distribution was quantitatively characterized by three metrics: burst ratio, peak location and peak area. 5-HTP shifted the IRT distribution peak toward longer IRT durations, increased reinforcement rate and decreased response rate. The profile of the IRT distribution was not disrupted by 5-HTP. Diazepam disrupted the IRT distribution and increased bursting. In general, the arylpiperazine, 5-HT1A compounds increased reinforcement rate, decreased response rate and disrupted the profile of the IRT distribution. The effects of the four arylpiperazine 5-HT1A compounds on the IRT distribution profile were different from the AD profile of 5-HTP and the benzodiazepine anxiolytic profile of diazepam. Disruption of the IRT distribution by buspirone, gepirone, ipsapirone and zalospirone may result from decreased 5-HT transmission mediated by the presynaptic, somatodendritic 5-HT1A receptor.

Preclinical and clinical evidence suggests that serotonin may be involved in the pathophysiology of autistic disorder. Drugs which facilitate serotonin function have demonstrated relative efficacy in improving social relatedness, diminishing aggressivity, and reducing repetitive thoughts and behaviors in some patients with autism. This single-case report reviews the rationale for the use of lithium augmentation of a serotonin uptake inhibitor, fluvoxamine, in the treatment of autism. A 27-year-old man with autistic disorder was treated with fluvoxamine 200 mg (3 mg/kg) daily for 12 weeks and showed minimal clinical response. When lithium 900 mg daily (0.7 meq/L) was added to the fluvoxamine, a substantial clinical improvement in social relatedness and a marked reduction in aggressive and impulsive behavior were observed after two weeks. At the end of four weeks of treatment with fluvoxamine and lithium, the patient was rated as much improved on the several rating scales. He maintained this clinically mean...

Objective To present electron micrographs of lung tissue obtained from a patient exposed to high ventilatory pressures in the context of pulmonary dysfunction and pulmonary hypertension. Design Case report. Setting Adult intensive care unit of a university-affiliated teaching hospital. Patients A patient exposed to high-pressure mechanical ventilation during support for acute respiratory distress syndrome; the acute respiratory distress syndrome in this case was secondary to septic shock. Measurements and main results Scanning electron micrographs of lung tissue, focusing on the internal alveolar surfaces. Findings Multiple gross disruptions of the alveolar walls, suggestive of stress fractures. Conclusion High-pressure mechanical ventilation may promote fracturing of the alveolar blood:airspace barrier.

Group II metabotropic glutamate (mGlu) receptor agonists were efficacious in randomized clinical research trials for schizophrenia and generalized anxiety disorder. The regional quantification of mGlu(2) and mGlu(3) receptors remains unknown. A selective and structurally novel mGlu(2/3) receptor agonist, 2-amino-4-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY459477) was tritiated and the distribution of mGlu(2) and mGlu(3) receptors was studied in transgenic mice lacking either mGlu(2), mGlu(3) or both receptors. LY459477 is an agonist with 1-2 nM potency for rodent and human mGlu(2) and mGlu(3) receptors. The functional selectivity of LY459477 was demonstrated by over 640-fold selectivity and the displacement binding selectivity was greater than 320-fold for all glutamate receptors except mGlu(6) (∼230-fold). More than 1000-fold selectivity was demonstrated for all non-glutamate receptors known to be targeted by antipsychotic drugs. Like atypical antipsychotic drugs, LY459477 reversed in vitro electrophysiological effects of a serotonergic hallucinogen and behavioral effects of phencyclidine or amphetamine. There was virtually no binding of [(3)H]LY459477 to any brain region in mice with a deletion of both mGlu(2) and mGlu(3) receptors. Regions enriched in mGlu(2) receptors included the medial prefrontal cortex, select hippocampal regions, the medial mammillary nucleus, the medial habenula, and the cerebellar granular cell layer. Regions enriched in mGlu(3) receptors were the dorsolateral entorhinal cortex, the hippocampal CA1 field, the piriform cortex, the substantia nigra, the thalamic reticular nucleus, and primary sensory thalamic nuclei. These findings suggest [(3)H]LY459477 should be a useful tool to further define the role of mGlu(2) and mGlu(3) receptors throughout the brain with respect to major neuropsychiatric syndromes. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.