Copper pro-inflammatory properties have been confirmed by using p

Copper pro-inflammatory properties have been confirmed by using primary neurons. (C) 2009 Elsevier Inc. All rights reserved.”
“To determine the underlying substrate utilization mechanism in the logistic equation for batch microbial growth by revealing the relationship between the logistic and Monod kinetics. Also, to determine the logistic rate constant in terms of Monod kinetic


The logistic equation used to describe batch microbial growth was related to the Monod kinetics and found to be first-order in terms of the substrate and biomass concentrations. The logistic equation LY411575 constant was also related to the Monod kinetic constants. Similarly, the substrate

utilization kinetic equations were derived by using the logistic growth equation and related to the Monod kinetics.

It is revaled that the logistic growth equation is a special form of the Monod growth kinetics when substrate limitation is first-order with respect to the substrate concentration. The logistic rate constant (k) is directly proportional to the maximum specific growth rate constant (mu(m)) and initial substrate concentration (S(0)) and also inversely related to the saturation constant (K(s)).

The semi-empirical logistic equation can be used instead of Monod kinetics at low substrate concentrations to describe batch microbial growth using the relationship between the logistic rate constant and the Monod kinetic

“Sodium channel blocker buy ICG-001 insecticides (SCBIs), such as indoxacarb and metaflumizone, are a new class of insecticides with a mechanism of action different from those of other insecticides that target sodium channels. SCBIs block sodium channels in a manner similar to local anesthetics (LAs) such as lidocaine. Several residues, particularly F1579 and Y1586, in the sixth transmembrane segment (S6) of domain IV (IV) of rat Na(v)1.4 sodium Selleck SU5402 channels are required for the action of LAs and SCBIs and may form part of overlapping receptor sites. However, the binding site for SCBIs in insect sodium channels remains undefined. We used site-directed mutagenesis, the Xenopus laevis oocyte expression system, and the two-electrode voltage clamp technique to study the effects on SCBI activity of mutating F1817 and Y-1824 (analogous to those residues identified in mammalian sodium channels) to alanine, in the voltage-sensitive sodium channel of the German cockroach, Blattella germanica. The mutant channels showed no effect or a marked increase in channel sensitivity to both DCJW (the active metabolite of indoxacarb) and metaflumizone.


antibodies (mAbs) are in widespread us


antibodies (mAbs) are in widespread use for the treatment of cancer. Their success as cancer therapeutics relies substantially on their ability to engage the immune system. Specifically, Fc-receptor-expressing immune cells mediate the killing of tumor cells by mAbs. Stimulation of these immune effector cells might therefore represent a promising strategy to enhance the therapeutic potential of mAbs. For instance, stimulation of natural killer cells, gamma delta T cells, macrophages, or dendritic cells can be used Tubastatin A in vivo to enhance antibody-dependent cellular cytotoxicity, phagocytosis or even tumor vaccine effects. Here, we review several ways to improve the antitumor efficacy of mAbs by combining them with therapies that are directed against immune effector cells.”
“Brain-derived neurotrophic factor (BDNF) plays important roles in the development, maintenance, and plasticity of the mammalian forebrain. These functions include regulation of neuronal maturation and survival, axonal and dendritic arborization, synaptic efficacy, and modulation of complex behaviors including

depression and spatial learning. Although analysis of mutant mice has helped establish essential developmental see more functions for BDNF, its requirement in the adult is less well documented. We have studied late-onset forebrain-specific BDNF knockout (CaMK-BDNFKO) mice, in which BDNF is lost primarily from the cortex and hippocampus in early adulthood, well after BDNF expression has begun in these structures. We found that although CaMK-BDNFKO mice grew at a normal rate and can survive more than a year, they had smaller brains than wild-type siblings. The CaMK-BDNFKO mice had generally normal behavior in tests for ataxia and anxiety, but displayed

reduced spatial learning ability in the Morris water task and increased depression in the Porsolt swim test. These behavioral deficits were very similar to those we previously described in an early-onset forebrain-specific BDNF knockout. To identify an anatomical correlate of the abnormal behavior, we quantified dendritic spines in cortical neurons. The spine density of CaMK-BDNFKO mice was normal at P35, but by P84, there was a 30% reduction in spine density. The strong similarities we find between A-1155463 nmr early- and late-onset BDNF knockouts suggest that BDNF signaling is required continuously in the CNS for the maintenance of some forebrain circuitry also affected by developmental BDNF depletion. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Biologically important human proteins often require mammalian cell expression for structural studies, presenting technical and economical problems in the production/purification processes. We introduce a novel affinity peptide tagging system that uses a low affinity anti-peptide monoclonal antibody.

Reduction of 5-HT signaling has been suggested to enhance dopamin

Reduction of 5-HT signaling has been suggested to enhance dopaminergic responses in animal CHIR99021 models of psychosis. An intriguing naturalistic strategy to reduce 5-HT brain content is afforded by the dietary restriction to its

precursor, l-tryptophan (TRP).

Objective We investigated the impact of a TRP-deficient diet in rats on the prepulse inhibition of the startle (PPI), a measure of sensorimotor gating which is typically impaired by psychotomimetic substances.

Materials and methods After either short-term (6 h) or long-term (14 days) TRP deprivation, rats were tested for startle reflex and PPI. Moreover, we assessed the impact of both TRP deprivation regimens on PPI reduction induced by the psychotomimetic substance d-amphetamine (AMPH).

Results Both TRP-deficient regimens failed to significantly affect PPI responses. However, chronic, but not short-term, TRP-deficient diet induced a significant sensitization to the effects of AMPH (1.25-2.5 mg/kg, subcutaneous). The enhanced predisposition to PPI disruption elicited by prolonged TRP deprivation was completely reversed 24 h after reinstatement

of TRP in the diet, as well as pretreatment with antipsychotic drugs haloperidol (0.1 mg/kg, intraperitoneal) and clozapine (5 mg/kg, intraperitoneal), which exert their therapeutic action mostly through blockade of DA D(2) receptors.

Conclusions The present results confirm and extend previous findings

on the impact of serotonergic signaling in the modulation AZD4547 concentration of DA transmission in schizophrenia and point to chronic TRP deprivation as a potential model of environmental manipulation that may produce a sensitization to psychotic-like symptoms induced by dopaminergic activation.”
“BACKGROUND AND IMPORTANCE: To present the feasibility of using the Ascent balloon, a new double-lumen remodeling balloon, for a new 2-in-1 technique allowing coiling through the lumen of the balloon without the use of an additional coiling microcatheter. Remodeling technique had enlarged the indications for endovascular treatment of intracranial aneurysm. Nevertheless, one Levetiracetam of the limitations of this technique is that it requires using 2 devices in the same parent artery.

CLINICAL PRESENTATION: A 55-year-old woman presented with a 7.7 x 4.5-mm incidental anterior communicating artery aneurysm. Only 1 A1 segment (left side) was patent on the cerebral angiogram. A 6F Fargo Max guiding catheter was positioned in the left petrous internal carotid artery. The Ascent balloon was placed in front of the neck of the aneurysm after navigation on a Traxcess 0.014-in guidewire. Coiling of the aneurysm sac was performed via 1 lumen of the device under iterative inflations of the balloon through the second lumen.

“Objective: The objective was to compare the


“Objective: The objective was to compare the

medium- and long-term outcomes for pericardial monocusp valves, polytetrafluoroethylene (Gore-Tex, WL Gore and Associates Inc, Flagstaff, Ariz) 0.1-mm monocusp valves, and bileaflet 0.1-mm polytetrafluoroethylene valves and their efficiency in the right ventricular outlet.

Methods: We reviewed all hand-sewn right ventricular outlet valves created by the author (Graham R. Nunn) in the setting of repaired tetralogy of Fallot or equivalent right ventricular outlet Foretinib molecular weight pathology when the native pulmonary valve could not be preserved. The valves were assessed by serial transthoracic echocardiography and more recently by magnetic resonance imaging angiography for late valve function. The bileaflet polytetrafluoroethylene valves were constructed in a standardized fashion from a semicircle of 0.1-mm polytetrafluoroethylene Akt inhibitor (the radius of which equaled the length of the outflow tract incision) that gave a lengthened free edge to the leaflets, central fixation of the free edge posteriorly just proximal to the branch pulmonary arteries, and generous augmentation of the outflow tract with polytetrafluctroethylene patch-plasty. The bileaflet configuration shortens the

closing time against the posterior wall, and the leaflets are forced to maintain their configuration without prolapse into the right ventricular outlet. The valve can be generously oversized in young children to try to avoid the need for replacement.

Results: A total of 54 patients met the selection criteria-22 patients received fresh autologous pericardial Bcl-w monocusps, 7 patients received polytetrafluoroethylene C (0.1-mm) monocusps, and 25 patients received bileaflet potytetrafluoroethylene (0.1-min) outlet valves. The pericardial valves have the longest follow-up, and all valves developed free pulmonary incompetence. Polytetrafluoroethylene monocusps had reliable competence early after surgery but progressed to pulmonary incompetence. The bileaflet polytetrafluoroethylene (0.1-mm) valves

have remained competent with regurgitant fractions of only 5% to 30% (magnetic resonance imaging angiography), and this has remained stable with time. The maximum follow-up for these valves is 5 years. No stenosis or peripheral emboli have been recognized, and no valves have been replaced to date.

Conclusion: Hand-sewn bileaflet polytetrafluoroethylene valves in the right ventricular outlet can reliably provide competence and maintain function in the medium term Their shape and size allow placement in young children with a reasonable expectation that they will remain competent with growth of the native annulus and not require replacement. Their durability is superior to the pericardial and polytetrafluoroethylene moriocusp valves in this series.”
“Obejctive: We sought to evaluate midterm functional and anatomic results after coronary artery surgical arterioplasty or bypass grafting in infants and children.

Here we show that a combination of ultra-high-field strength magn

Here we show that a combination of ultra-high-field strength magnetic resonance imaging (17.6 T, MRI) coupled with fluorescent microscopy (FLM) serves as a powerful tool for the in vivo imaging of cell homing within the BM. Ultra-high-field MRI can achieve high-resolution three-dimensional (3D) images (28 x 28 x 60 mu m(3)) of the BM in live mice, GSK621 datasheet sufficient to resolve anatomical changes in BM microstructures attributed to radiation damage. Following intra-arterial infusion

with dsRed-expressing BM cells, labeled with superparamagnetic iron oxides, both FLM and MRI could be used to follow initial homing and engraftment of donor HSC to a limited number of preferred sites within a few cell diameters of the calcified bone-he endosteal niche. Subsequent histology confirmed the fidelity and accuracy of MRI to create non-invasive, high-resolution 3D images of donor cell engraftment of the BM in living animals at the level of single-cell detection. Leukemia (2011) 25, 1223-1231; doi:10.1038/leu.2011.72; published online 15 April 2011″
“Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson’s disease

(PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested CRT0066101 in vitro the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients

and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. Selleckchem Quizartinib This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward.

These results demonstrate that Tax expression may allow premature

These results demonstrate that Tax expression may allow premature DNA replication in the presence of genomic lesions. Attempts to replicate in the presence of these lesions would result in gradual accumulation

learn more of mutations, leading to genome instability and cellular transformation.”
“Introduction: Clinical studies of patients treated with somatostatin-receptor (sstr)-targeted [DOTA(0)-Tyr(3)]-octretide (DOTATOC) labeled with Lu-177 and Y-90 have shown overall response rates in the range of 9-33%. This study evaluates the potential for combination therapy with gemcitabine in an effort to improve clinical outcomes.

Methods: Human pancreatic adenocarcinoma Capan-2, rat pancreatic cancer AR42J and human small cell lung cancer NCI-H69

cells were each treated with 1 mu g/ml gemcitabine for 4 days followed by replacement of the medium alone for four additional days. Cell cycle and direct receptor-uptake studies were performed to study the effects of gemcitabine pretreatment and Lu-177-DOTATOC radionuclide therapy. Parallel control studies were performed with receptor-non-targeted Lu-177-DOTA and DOTATOC.

Results: Cells treated with gemcitabine for 4 days showed a down-regulation of sstr expression as determined by 177Lu-DOTATOC uptake. see more However, after 4 days of additional growth in absence of gemcitabine, the uptake of 177Lu-DOTATOC was 1.5-3 times greater than that of the untreated control cells. In gemcitabine-pretreated Capan-2 cells, 84% of the cell population was in the G(2)M phase of the cell cycle. Due to sstr up-regulation and cell cycle modulations, synergistic effects of gemcitabine Florfenicol pretreatment were observed in cell viability and apoptosis assays. Lu-177-DOTATOC resulted in two to three times greater apoptosis in gemcitabine-pretreated Capan-2 cells compared to the untreated cells.

Conclusion: Gemcitabine

pretreatment up-regulates sstr expression and acts as a radiosensitizer through cell cycle modulation. The rational combination of gemcitabine and sstr-targeted radiopharmaceuticals represents a promising chemoratiation therapeutic tool with great potential to improve clinical outcomes and, thus, merits further study. (C) 2008 Elsevier Inc. All rights reserved.”
“Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, an emerging disease characterized by atypical pneumonia. Using a yeast two-hybrid screen with the nucleocapsid (N) protein of SARS-CoV as a bait, the C terminus (amino acids 251 to 422) of the N protein was found to interact with human elongation factor 1-alpha (EF1 alpha), an essential component of the translational machinery with an important role in cytokinesis, promoting the bundling of filamentous actin (F-actin). In vitro and in vivo interaction was then confirmed by immuno-coprecipitation, far-Western blotting, and surface plasmon resonance.

The number and diversity of identified endocrine factors from adi

The number and diversity of identified endocrine factors from adipose tissue (adipokines) is growing rapidly. Here,

I argue that a systems biology approach to understanding the robust multi-level signaling networks established by the adipose secretome will be crucial for developing efficient type 2 diabetes treatment. Recent advances in whole-genome association studies, global molecular profiling and quantitative modeling are currently fueling the emergence of this novel research strategy.”
“Dysfunctional N-methyl-D-aspartate (NMDA) receptor neurotransmission has been implicated in the pathophysiology of schizophrenia. It is thought that this abnormal functioning can be corrected by increasing availability of the NMDA co-agonist glycine through inhibition of glycine transporter type 1 (GlyT1). Herein is described the pharmacologic profile of RG1678, a potent and noncompetitive glycine reuptake inhibitor. In vitro, RG1678 noncompetitively inhibited TGF-beta inhibitor glycine uptake at human GlyT1 with a concentration exhibiting half-maximal inhibition (IC50) of 25 nM and competitively blocked [H-3]ORG24598

binding sites at human GlyT1b in membranes from Chinese hamster ovary cells. In hippocampal CA1 pyramidal cells, RG1678 enhanced NMDA-dependent long-term potentiation at 100 nM but not at 300 nM. In vivo, RG1678 dose-dependently increased cerebrospinal fluid and striatal levels of glycine measured by microdialysis in rats. Additionally RG1678 attenuated hyperlocomotion induced by the psychostimulant D-amphetamine or the NMDA receptor glycine site antagonist L-687,414 in mice. RG1678 also prevented the hyper-response to D-amphetamine challenge in rats treated chronically with phencyclidine, an NMDA receptor open-channel blocker. In the latter experiment, a decrease in ex vivo striatal [H-3]raclopride binding was also measured. These data demonstrate that RG1678 is Daporinad concentration a potent, noncompetitive glycine reuptake inhibitor that can modulate both glutamatergic and dopaminergic neurotransmission in animal experiments

that model aspects of schizophrenia.

This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’. (C) 2011 Elsevier Ltd. All rights reserved.”
“Mullerian mimicry, where groups of chemically defended species display a common warning color pattern and thereby share the cost of educating predators, is one of the most striking examples of ecological adaptation. Classic models of Mullerian mimicry predict that all unpalatable species of a similar size and form within a community should converge on a single mimetic pattern, but instead communities of unpalatable species often display a remarkable diversity of mimetic patterns (e.g. neotropical ithomiine butterflies).

Stimulation at this site is typically delivered at low frequencie

Stimulation at this site is typically delivered at low frequencies in contrast to the high frequency stimulation required for therapeutic benefit in the subthalamic nucleus. Therefore, we looked for and demonstrated evidence of low frequency synchronization of activity in the pedunculopontine nucleus of a patient with Parkinson’s disease that increased after treatment with dopamine and which might be mimicked by local deep brain stimulation at low frequency.”
“Purpose: We addressed the Quisinostat ic50 impact of stone density and size on the role of computerized tomography for diagnosing residual stones after percutaneous nephrolithotomy.

Materials and Methods: We prospectively evaluated

check details 100 renal units that underwent percutaneous nephrolithotomy. The study included 55 opaque and 45 lucent or faint stones. Patients were examined after the procedure by plain x-ray of the kidneys, ureters and bladder, linear tomography, ultrasound and spiral computerized tomography. Minute residual stones were defined as 1 or 2 caliceal stones less

than 5 mm, as measured by computerized tomography.

Results: Stone-free status was achieved in 38 renal units. Minute and significant residual stones were detected in 26 and 36 renal units, respectively. For faint and lucent stones sensitivity for overall stone detection was 100% for computerized tomography, 11.1% for plain x-ray, 22.2% for linear tomography and 22.2% for ultrasound (p < 0.05). Sensitivity for detecting significant residual stones was 100% for computerized tomography, 20% for plain x-ray, 33.3% for linear tomography and 20% for ultrasound (p < 0.05). For opaque stones sensitivity for overall stone detection was 100% for

computerized tomography, 62.9% for plain x-ray, 74.3% linear tomography and 48.6% for ultrasound (p < 0.05). Sensitivity for detecting significant residual stones was 100% for computerized tomography, 85.7% for plain x-ray (p not significant), 95.2% for linear tomography (p not significant) and 57.1% for ultrasound (p < 0.05).

Conclusions: Computerized tomography provides the most sensitive tool for detecting residual stones after percutaneous nephrolithotomy. Nevertheless, Selleckchem BAY 1895344 it should not be routinely performed in patients with opaque stones because it yields no statistically valuable increase in the diagnosis of significant residual stones compared with that of plain x-ray and linear tomography.”
“We studied Fos immunoreactivity within targets of the mesocorticolimbic dopamine systems at different stages of acquisition of heroin place conditioning. Fos was quantified in groups of rats after one or four exposures to 0.3-mg/kg heroin only, or to the conditioning compartment only, or to both heroin and the conditioning compartment, or to neither stimuli.

Poor cognitive performance was observed in the subjects taking

Poor cognitive performance was observed in the subjects taking PS-341 in vivo dimenhydrinate. We used two-channel near-infrared spectroscopy to investigate the effects of dimenhydrinate on the COS. With the one exception of shifting attention task in the left forehead, no significant difference was found between dimenhydrinate and placebo during the tasks of the test battery. Under placebo treatment,

on the other hand, CgA levels were significantly elevated during cognitive testing when compared with baseline. However, CgA levels were not significantly elevated above baseline following dimenhydrinate. The present study is one of the first to demonstrate that the first-generation antihistamine drugs altered the responses of salivary CgA during cognitive tasks. The changes in salivary CgA

secretion, as a result of dimenhydrinate administration, may serve as a sensitive biomarker of a psychological status such as a drug-induced sedation during the performance of a cognitive test battery. Further studies, however, are required to examine the usefulness of this sensitive biomarker in investigation of psychological agents during cognitive tasks. (c) 2007 Elsevier Inc. All rights reserved.”
“BACKGROUND AND IMPORTANCE: We present a patient with a cervical spine dural arteriovenous fistula associated with a radiculopial artery aneurysm at the same vertebral level presenting with subarachnoid hemorrhage.

CLINICAL PRESENTATION: A 45-year-old Native American man presented with sudden-onset severe headache, lethargy, and right hemiparesis. Computed tomography (CT) of the head showed subarachnoid hemorrhage

and hydrocephalus. A subsequent CT of the neck showed an anterior spinal subdural hematoma from C2 to C4 causing mild cord compression. Carotid and vertebral angiography failed to demonstrate an intracranial aneurysm, but showed a spinal dural arteriovenous fistula originating from the right vertebral artery at the C5 neuroforamen. The severity of the patient’s symptoms, atypical for rupture of a dural arteriovenous fistula, prompted more thorough angiographic evaluation. Thus, injection of the right thyrocervical trunk was performed, demonstrating a 4-mm JNJ-64619178 spinal radiculopial artery aneurysm. Following ventriculostomy, a hemilaminectomy from C4 to C7 was performed with disconnection of the fistula from its drainage system. Subsequent resection of the aneurysm, which was determined to be the cause of the hemorrhage, was accomplished. The patient improved neurologically and was discharged to rehabilitation.

CONCLUSION: Spinal cord aneurysms from a separate vascular distribution may coexist with spinal dural arteriovenous fistulas. In the setting of spinal hemorrhage, especially in situations with an atypical clinical presentation, comprehensive imaging is indicated to rule out such lesions.”
“Phosphatidylserine (PS)-containing liposomes (PSLs) strongly inhibit inflammatory bone loss in adjuvant arthritic (AA) rats.

Four weeks after SE, PLK and PNPO immunoreactivities in dentate g

Four weeks after SE, PLK and PNPO immunoreactivities in dentate granule cells were similar to those in control animals, while their immunoreactivities were markedly reduced in Cornu Ammonis 1 (CA1) pyramidal cells

due to neuronal loss. Linear regression analysis identified a direct proportional relationship between PLK/PNPO immunoreactivity and normalized population spike amplitude ratio in the dentate gyrus and the CA1 region as excluded the data obtained from 4 weeks after SE. These findings indicate PF-02341066 concentration that the upregulation of PLK and PNPO immunoreactivities in principal neurons may not be involved in gamma-aminobutyric acid (GABA)ergic inhibition, but rather in enhanced excitability during epileptogenic periods. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“The evolution of corpus callosum (CC) was integral find more to the development of higher cognitive processes and hemispheric specialization. An examination of CC morphology and organization across different primate species will further our understanding

of the evolution of these specified functions. Using magnetic resonance imaging (MRI) as a non-invasive technique to measure CC size and to approximate the degree of myelination in the corpus callosum, we report differences in CC morphology and organization in capuchin monkeys and chimpanzees, two divergent primate species that have independently evolved several behavioral and anatomical characteristics. Species differences in CC morphology were detected, with chimpanzees having a larger overall CC compared to capuchin monkeys. Additionally, chimpanzees had the genu as the largest subdivision; in capuchin monkeys, the genu and splenium were the largest subdivisions.

Sex differences in signal intensity were detected; capuchin monkey males had higher signal intensity values whereas chimpanzee females had higher signal intensity values. Thus, while capuchin monkeys and chimpanzees show some similarity in patterns of CC morphology, these species differ significantly in the regional organization of the CC. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background Because of the debate about whether second-generation antipsychotic drugs are better than first-generation antipsychotic drugs, we did a meta-analysis of randomised controlled trials to compare the effects of these two types of drugs in patients with schizophrenia.

Methods We compared nine second-generation antipsychotic drugs with first-generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation.

Findings We included 150 double-blind, mostly short-term, studies, with 21533 participants. We excluded open studies because they systematically favoured second-generation drugs. Four of these drugs were better than first-generation antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride -0.