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© 2023 Wiley Periodicals LLC.In this study, we have synthesized a series of 3-(pyridin-2-yl)-2-(pyridin-2-ylimino)thiazolidin-4-ol derivatives regioselectively from 2-iminothiazolidin-4-ones using LiAlH4 at room temperature. Due to the presence of the restricted rotation around the N3-Caryl single bond, the formation of M/P isomers was observed. The OH group of the hemiaminal was found to orient itself on the same side with pyridyl nitrogen during this restricted rotation to form an intramolecular hydrogen bond, which was demonstrated by the computational DFT study. This orientation presumably inhibited the occurrence of dehydration and stabilized the molecule.

In 2003, the Society of Surgical Oncology (SSO) initiated a breast surgical oncology fellowship, which has now grown to 60 SSO accredited programs as of 2021. Limited knowledge exists on the traits of successful applicants and the factors influencing the rank list.A web-based, anonymous survey was sent to all SSO Breast Surgical Oncology Fellowship program directors. The survey consisted of 26 questions. Descriptive statistics were used to analyze survey responses and evaluate impact on applicant interview and rank list.Thirty-four programs (57% response rate) completed the survey. Programs received an average of 70 applications and granted 24 interviews. Most programs reported a minimum ABSITE cut-off score (n = 28, 82%) and a defined publication requirement (n = 22, 65%), including a first-author requirement (n = 18, 53%) to extend an invitation to interview. For postinterview rank, applicant interpersonal skills were highly valued. The interview was the most important aspect for the rank list.Many programs have ABSITE and publication thresholds before offering an interview. Upon receiving interview invitation, the applicant's interview performance, interpersonal skills, and letters of recommendation were the most important aspect in rank list decision making.

Purpose Ventricular tachycardia (VT) is a rapid, abnormal heart rhythm that can lead to sudden cardiac death. Current treatment options include antiarrhythmic drug therapy and catheter ablation, both of which have only modest efficacy and have potential complications. Cardiac radiosurgery has the potential to be a noninvasive and efficient treatment option for VT. Cardiac motion, however, must be accounted for to ensure accurate dose delivery to the target region. Cardiac synchronized volumetric modulated arc therapy (CSVMAT) aims to minimize the dose delivered to normal tissues by synchronizing beam delivery with a cardiac signal, irradiating only during the quiescent intervals of the cardiac cycle (when heart motion is minimal) and adjusting the beam delivery speed in response to heart rate changes. Methods A CSVMAT plan was adapted from a conventional VMAT plan and delivered on a Varian TrueBeam linear accelerator. The original VMAT plan was divided into three interleaved CSVMAT phases, each consisting of alternating beam-on and beam-off segments synchronized to a sample heart rate. Trajectory log files were collected for the original VMAT and CSVMAT deliveries and the dose distributions were measured with Gafchromic EBT-XD film. Results Analysis of the trajectory log files showed successful synchronization with the sample cardiac signal. Film analysis comparing the original VMAT and CSVMAT dose distributions returned a gamma passing rate of 99.14% (2%/2 mm tolerance). Conclusions The film results indicated excellent agreement between the dose distributions of the original and cardiac synchronized beam deliveries. This study demonstrates a proof of principle cardiac synchronization strategy for precise radiation treatment plan delivery and adjustment to a variable heart rate. The cardiac synchronized technique may be advantageous in radioablation for VT.

WOS: 000486972406051 [No abstract available]

Background The aim of this study was to investigate whether Helicobacter pylori plays a role in the pathogenesis and severity of non-cystic fibrosis bronchiectasis, and its relationship with gastroesophageal reflux (GER). Methods Forty-one patients and 16 controls between 5 and 18 years of age were enrolled. H. pylori was investigated on polymerase chain reaction and culture in gastric juice (GJ) and bronchoalveolar lavage fluid (BALF). Urea breath test (UBT) was also used for defining H. pylori infection. GER was detected on 24 h pH monitoring or scintigraphy. Computed tomography (CT) scoring was used to quantify the severity and extent of bronchiectasis. Results Nine patients (22%) in the bronchiectasis group (BG) and three patients (18.8%) in the control group (CG) had H. pylori-positive BALF. Sixteen BG patients (39%) and seven CG patients (43.8%) had H. pylori-positive GJ. UBT was positive in 11 BG patients (26.8%) and in three CG patients (18.8%). H. pylori positivity in BALF, GJ and UBT was not significantly different between the two groups (P > 0.05). Six patients with GER and five patients without GER in BG had H. pylori-positive BALF and GJ (P = 0.827). No association was found between BALF H. pylori positivity and forced expiratory volume in 1 s (FEV1) in BG. CT score was significantly higher in BG patients with H. pylori-positive compared with H. pylori-negative BALF (P < 0.05). Conclusions Helicobacter pylori is not associated with the pathogenesis of bronchiectasis but it may be responsible for the severity of the disease.

Aggression, which is defined as a behavior causing harm or pain, is a behavioral pattern typically expected in children and adolescents who are involved in criminal activities. The aim of this study was to examine the relationship between aggression and self-injurious behavior (SIB) in children and adolescents. The study was performed in 295 cases which were sent for medicolegal examination. The mean age of the subjects was 14.27 ± 1.05 years (age range 10-18 years). The aggression levels of the subjects were determined using the Aggression Questionnaire (AQ), which is an updated form of the Buss-Durkee Hostility Inventory. The mean total AQ score of the subjects with and without SIB was 78.04 ± 21.0 and 62.75 ± 18.05, respectively (p < 0.01). There were significant statistical differences between the two groups with respect to their subscale scores (p < 0.01). It was concluded that the levels of aggression increased in children and adolescents who were involved in criminal activities when the SIBs increased.

Purpose: To establish the clinical acceptability of universal Monte Carlo phase–space data for the 10XFFF (flattening filter free) photon beam on the Varian TrueBeam Linac, including previously unreported data for small fields, output factors, and inhomogeneous media. The study was particularly aimed at confirming the suitability for use in simulations of lung stereotactic ablative radiotherapy treatment plans. Methods: Monte Carlo calculated percent depth doses (PDDs), transverse profiles, and output factors for the TrueBeam 10 MV FFF beam using generic phase–space data that have been released by the Varian MC research team were compared with in-house measurements and published data from multiple institutions (ten Linacs from eight different institutions). BEAMnrc was used to create field size specific phase–spaces located underneath the jaws. Doses were calculated with DOSXYZnrc in a water phantom for fields ranging from 1 × 1 to 40 × 40 cm2. Particular attention was paid to small fields (down to 1 × 1 cm2) and dose per pulse effects on dosimeter response for high dose rate 10XFFF beams. Ion chamber measurements were corrected for changes in ion collection efficiency (P ion) with increasing dose per pulse. MC and eclipse anisotropic analytical algorithm (aaa) calculated PDDs were compared to Gafchromic film measurement in inhomogeneous media (water, bone, lung). Results: Measured data from all machines agreed with Monte Carlo simulations within 1.0% and 1.5% for PDDs and in-field transverse profiles, respectively, for field sizes >1 × 1 cm2 in a homogeneous water phantom. Agreements in the 80%–20% penumbra widths were better than 2 mm for all the fields that were compared. For all the field sizes considered, the agreement between their measured and calculated output factors was within 1.1%. Monte Carlo results for dose to water at water/bone, bone/lung, and lung/water interfaces as well as within lung agree with film measurements to within 2.8% for 10 × 10 and 3 × 3 cm2 field sizes. This represents a significant improvement over the performance of the eclipse aaa. Conclusions: The 10XFFF phase–space data offered by the Varian Monte Carlo research team have been validated for clinical use using measured, interinstitutional beam data in water and with film dosimetry in inhomogeneous media.

Item does not contain fulltext Objective Glutamate and γ-aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical-thalamocortical network, involved in normal and pathologic oscillations such as spike-wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats. Methods Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine. Results Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose-dependent manner when injected into the cortex. Intracortical co-injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co-injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min. Significance These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence-enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA. 11 p.

In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto acetylcholine removed imprinted polymer and acetylcholine containing polymer. First, the polymers were produced with acetylcholine, substrate of AChE, by dispersion polymerization. Then, the enzyme was immobilized onto the polymers by using two different methods: In the first method (method A), acetylcholine was removed from the polymer, and then AChE was immobilized onto this polymer (acetylcholine removed imprinted polymer). In the second method (method B), AChE was immobilized onto acetylcholine containing polymer by affinity. In method A, enzyme-specific species (binding sites) occurred by removing acetylcholine from the polymer. The immobilized AChE reached 240% relative specific activity comparison with free AChE because the active enzyme molecules bounded onto the polymer. Transmission electron microscopy results were taken before and after immobilization of AChE for the assessment of morphological structure of polymer. Also, the experiments, which include optimum temperature (25–65°C), optimum pH (3–10), thermal stability (4–70°C), kinetic parameters, operational stability and reusability, were performed to determine the characteristic of the immobilized AChE. Copyright © 2015 John Wiley & Sons, Ltd.

Background Brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations and complications. Neurobrucellosis is an uncommon and serious complication of pediatric brucellosis. Methods We describe seven cases of neurobrucellosis. Results Ataxia (one patient), diplopia (one patient) and hearing loss (one patient) were among the neurological signs and symptoms. The most common diagnoses were acute meningitis and meningoencephalitis. Five of the patients fully recovered, one was lost to follow up and the other had hearing loss as a sequela. Conclusion Neurobrucellosis should be kept in mind in patients with any neurological or neuropsychiatric diseases who live in endemic areas of brucellosis.

A Monte Carlo (MC) validation of the vendor‐supplied Varian TrueBeam 6 MV flattened (6X) phase‐space file and the first implementation of the Siebers‐Keall MC MLC model as applied to the HD120 MLC (for 6X flat and 6X flattening filterfree (6X FFF) beams) are described. The MC model is validated in the context of VMAT patient‐specific quality assurance. The Monte Carlo commissioning process involves: 1) validating the calculated open‐field percentage depth doses (PDDs), profiles, and output factors (OF), 2) adapting the Siebers‐Keall MLC model to match the new HD120‐MLC geometry and material composition, 3) determining the absolute dose conversion factor for the MC calculation, and 4) validating this entire linac/MLC in the context of dose calculation verification for clinical VMAT plans. MC PDDs for the 6X beams agree with the measured data to within 2.0% for field sizes ranging from 2 × 2 to 40 × 40 cm2. Measured and MC profiles show agreement in the 50% field width and the 80%‐20% penumbra region to within 1.3 mm for all square field sizes. MC OFs for the 2 to 40 cm2 square fields agree with measurement to within 1.6%. Verification of VMAT SABR lung, liver, and vertebra plans demonstrate that measured and MC ion chamber doses agree within 0.6% for the 6X beam and within 2.0% for the 6X FFF beam. A 3D gamma factor analysis demonstrates that for the 6X beam, > 99% of voxels meet the pass criteria (3%/3 mm). For the 6X FFF beam, > 94% of voxels meet this criteria. The TrueBeam accelerator delivering 6X and 6X FFF beams with the HD120 MLC can be modeled in Monte Carlo to provide an independent 3D dose calculation for clinical VMAT plans. This quality assurance tool has been used clinically to verify over 140 6X and 16 6X FFF TrueBeam treatment plans. PACS number: 87.55.K‐

Background To compare retrobulbar blood flow in patients with central serous chorioretinopathy (CSC) and healthy subjects using color Doppler ultrasonography. Methods Thirty patients (age 23–54 years) with a first episode of acute CSC and 30 healthy controls (age 30–44 years) were evaluated. The peak systolic blood flow velocity, end-diastolic velocity (EDV), resistance index (RI), and pulsatility index (PI) were measured in the ophthalmic, posterior ciliary, and central retinal arteries. Results The posterior ciliary and central retinal artery EDV were lower in the patient group than in the control group, whereas RI and PI values were significantly higher (p

The purposes of this study were to evaluate the ability of a group of third-year dental students without any endodontic clinical experience to use the ProTaper Instruments (Dentsply Maillefer) to decrease the amount of straightening of curved canals on human molar teeth and to determine the incidence of instrument fractures and instrumentation time. Thirty-one undergraduate dental students in Turkey received a training session. The students prepared a total of 144 root canals in human mandibular or maxillary molar teeth with ProTaper. Fifty-six teeth were excluded due to unreadable image, misinformation, or straight or severe curve. Using pre- and post-preparation digital radiographs, the straightening of curved root canals was investigated. Loss of working length and incidence of fracture were also noted. A total of eighty-eight curved root canals were selected. Mesiobuccal or mesiolingual roots with curvatures of between 20° and 43° as assessed by Schneider's method and working length of between 15 mm and 22.5 mm were included in the study. The means of the curved root canals before and after the instrumentation were 29.5° ± 6° and 27° ± 6.3°, respectively. The means of the working length before and after the instrumentation were 19 mm ± 2.1 mm and 18.3 mm ± 1.9 mm, respectively. A statistically significant difference between straightening of curved root canals and loss of working length was found between before and after instrumentation (p

Metabotropic glutamate (mGlu) receptors are positioned at synapses of the thalamocortical network that underlie the development of spike-and-wave discharges (SWDs) associated with absence epilepsy. The modulatory role of individual mGlu receptor subtypes on excitatory and inhibitory synaptic transmission in the cortico-thalamo-cortical circuitry makes subtype-selective mGlu receptor ligands potential candidates as novel antiabsence drugs. Some of these compounds are under clinical development for the treatment of numerous neurologic and psychiatric disorders, and might be soon available for clinical studies in patients with absence seizures refractory to conventional medications. Herein we review the growing evidence that links mGlu receptors to the pathophysiology of pathologic SWDs moving from the anatomic localization and function of distinct mGlu receptor subtypes in the cortico-thalamo-cortical network to in vivo studies in mouse and rat models of absence epilepsy.

The aim of this study was to present the characteristics of medicolegal autopsies of fatal poisonings in Trabzon (Turkey), performed from 1998 to 2008, to contribute to the available data on this topic. A retrospective study of the forensic records and the toxicological data of all autopsies performed over that period revealed that 285 cases (6.34%) of the 4492 total autopsies performed were attributed to fatal poisoning. Major toxic substances were classified in five categories as follows: carbon monoxide (CO), insecticides, prescription medications, narcotic drugs, and alcohol (methyl and ethyl). CO was the most frequent cause of death (63.2%), followed by insecticides (17.2%), prescription medications and narcotic drugs (9.8%), alcohol (7.7%), and others (mushroom, rodenticide, and botulism) (2.1%). Ages of the patients ranged from 1 to 86 years (21.55 ± 36.56).

This article examines the remittance patterns of Cameroonians residing in Aarhus, Denmark and discusses the findings in relation to those from earlier studies on migrants’ remittances. Based on analyses of the inclination of these Cameroonians to support development projects in Cameroon, it is argued that a strengthened partnership between local non-state actors in Cameroon and the Cameroonian diaspora will significantly improve the role remittances can play in the country’s development. The article also highlights the framework, benefits and challenges of such potential partnership and suggests ways in which remittances from the Cameroonian diaspora in particular and African migrants in general, could be effectively channelled beyond migrants’ families to further the continent’s development drive.

Hybrid multilevel inverters have emerged as attractive power conversion systems at medium voltage levels, which are structured by cascaded series inverters having different internal DC bus voltages. This scheme therefore provides the capability to produce higher voltages at higher speeds with low switching losses and high conversion efficiency. The fundamentals and importance of hybrid multilevel systems can be easily enhanced by the undergraduate with visual learning and laboratory studies. However, the students cannot be able to implement the peripheral interface controller (PIC)-based projects sufficiently. In this paper, the simulation models and experimental setup of a hybrid multilevel inverter are presented in detail. From the theoretical and experimental experience obtained from this study, the students and engineers can provide more analytical opportunities for studying control algorithms of PIC controlled power electronics projects. This will provide the students to reinforce their lectures and laboratory studies. (c) 2010 Wiley Periodicals, Inc. Comput Appl Eng Educ 20: 445453, 2012

Purpose: Genetically epileptic WAGRij rats develop spontaneous absence-like seizures after 3 months of age. We used WAGRij rats to examine whether absence seizures are associated with changes in the expression of type-1 cannabinoid (CB1) receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of "presymptomatic" 2-month old and "symptomatic" 8-month-old WAGRij rats relative to age-matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB1 receptor affects absence seizures. We recorded spontaneous spike-wave discharges (SWDs) in 8-month old WAGRij rats systemically injected with the potent CB1 receptor agonist, R(+)WIN55,212-2 (3-12 mgkg, s.c.), given alone or combined with the CB1 receptor antagonistinverse agonist, AM251 (12 mgkg, s.c.). Results: Data showed a reduction of CB1 receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB 1 receptor protein levels in ventral basal thalamic nuclei of 8-month-old WAGRij rats, as compared with age-matched ACI control rats. In vivo, R(+)WIN55,212-2 caused a dose-dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB 1 receptor agonists. Both effects were reversed or attenuated when R(+)WIN55,212-2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB1 receptors within the thalamic-cortical-thalamic network, and raise the interesting possibility that CB1 receptors are targeted by novel antiabsence drugs.

Purpose: A Monte Carlo(MC) based QA process to validate the dynamic beam delivery accuracy for Varian RapidArc™ (Varian Medical Systems, Palo Alto, CA) using Linac delivery log files (DynaLog) is presented. Using DynaLog file analysis and MC simulations, the goal of this article is to (a) confirm that adequate sampling is used in the RapidArc optimization algorithm (177 static gantry angles) and (b) to assess the physical machine performance [gantry angle and monitor unit (MU) delivery accuracy]. Methods: Ten clinically acceptable RapidArc treatment plans were generated for various tumor sites and delivered to a water-equivalent cylindrical phantom on the treatment unit. Three Monte Carlo simulations were performed to calculate dose to the CT phantom image set: (a) One using a series of static gantry angles defined by 177 control points with treatment planning system (TPS) MLC control files (planning files), (b) one using continuous gantry rotation with TPS generated MLC control files, and (c) one using continuous gantry rotation with actual Linac delivery log files. Monte Carlo simulated dose distributions are compared to both ionization chamber point measurements and with RapidArc TPS calculated doses. The 3D dose distributions were compared using a 3D gamma-factor analysis, employing a 3 % ∕ 3 mm distance-to-agreement criterion. Results: The dose difference between MC simulations, TPS, and ionization chamber point measurements was less than 2.1%. For all plans, the MC calculated 3D dose distributions agreed well with the TPS calculated doses (gamma-factor values were less than 1 for more than 95% of the points considered). Machine performance QA was supplemented with an extensive DynaLog file analysis. A DynaLog file analysis showed that leaf position errors were less than 1 mm for 94% of the time and there were no leaf errors greater than 2.5 mm . The mean standard deviation in MU and gantry angle were 0.052 MU and 0.355°, respectively, for the ten cases analyzed. Conclusions: The accuracy and flexibility of the Monte Carlo based RapidArc QA system were demonstrated. Good machine performance and accurate dose distribution delivery of RapidArc plans were observed. The sampling used in the TPS optimization algorithm was found to be adequate.

Background: Pulmonary complications are the most frequent cause of postoperative morbidity and mortality in upper abdominal surgery (UAS). We aimed to examine the influence of possible preoperative, operative and postoperative risk factors on the development of early postoperative pulmonary complications (POPC) after UAS. Methods: A prospective study of 60 consecutive patients was conducted who underwent elective UAS in general surgical unit. Each patient’s preoperative respiratory status was assessed by an experienced chest physician using clinical examination, chest radiographs, spirometry and blood gas analysis . Anaesthetical risks, surgical indications, operation time, incision type, duration of nasogastric catheter and mobilization time were noted. Forty-eight hours after the operation, pulmonary examinations of the patients were repeated. Results: Postoperative pulmonary complications were observed in 35 patients (58.3%). The most common complication was pneumonia, followed by pneumonitis, atelectasis, bronchitis, pulmonary emboli and acute respiratory failure. The presence of preoperative respiratory symptoms and the spirometric parameter of forced expiratory volume in 1 s/forced vital capacity were the most valuable risk factors for early prediction of POPC. The sensitivity, specificity and diagnostic efficiency of the presence of preoperative respiratory symptoms in the POPC prediction were 70, 61 and 66%, respectively. Conclusion: We recommend a detailed pulmonary examination and spirometry in patients who will undergo UAS by chest physicians to identify the patients at high risk for POPC, to manage respiratory problems of the patients before surgery and also to help surgeons to take early measures in such patients before a most likely POPC occurrence. Improvement of lung function in those patients at risk for POPC before operation may decrease morbidity in surgical patients.

Several lines of evidence indicate a role for neurokinin3 receptors (NK3-Rs) in behavioural activation and mechanisms governing reinforcement processes. In this study we investigated the effect of pretreatment with the NK3-R antagonist, SR142801, (0.2 and 2.0 mg/kg) on the cocaine-induced (10.0 mg/kg i.p.) increase in extracellular dopaminergic activity in the nucleus accumbens (NAc). In vivo microdialysis in the NAc of freely moving rats showed that cocaine increased concentrations of dopamine (DA) to approximately 350% in the core and approximately 450% in the shell. Pre-treatment with SR142801 significantly potentiated this effect in the core (to approximately 550%), whereas this effect was not found in the shell. We also investigated the effects of NK3-Rs antagonism on cocaine-induced hyperactivity and conditioned place preference. SR142801 blocked the hyperactivity, but neither the conditioned place preference nor the conditioned locomotor activity induced by cocaine, although there was a slight tendency towards a reduced place preference. When given alone, SR142801 had no effects on behaviour or extracellular dopamine concentrations in any of the structures investigated. These data provide evidence for a contribution of NK3-Rs in the acute behavioural and neurochemical effects of cocaine, involving dopaminergic activity in the core of the nucleus accumbens.

Antidepressant drugs have a clinical latency that correlates with the development of neuroadaptive changes, including down-regulation of β-adrenergic receptors in different brain regions. The identification of drugs that shorten this latency will have a great impact on the treatment of major depressive disorders. We report that the time required for the antidepressant imipramine to reduce the expression of β-adrenergic receptors in the hippocampus is reduced by a co-administration with centrally active ligands of type 2/3 metabotropic glutamate (mGlu2/3) receptors. Daily treatment of mice with imipramine alone (10 mg/kg, i.p.) reduced the expression of β-adrenergic receptors in the hippocampus after 21 days, but not at shorter times, as assessed by western blot analysis of β1-adrenergic receptors and by the amount of specifically bound [3H]CGP-12177, a selective β-adrenergic receptor ligand. Down-regulation of β-adrenergic receptors occurred at shorter times (i.e. after 14 days) when imipramine was combined with low doses (0.5 mg/kg, i.p.) of the selective mGlu2/3 receptor agonist LY379268, or with the preferential mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.). Higher doses of LY379268 (2 mg/kg, i.p.) were inactive. This intriguing finding suggests that neuroadaptation to imipramine – at least as assessed by changes in the expression of β1-adrenergic receptors – is influenced by drugs that interact with mGlu2/3 receptors and stimulates further research aimed at establishing whether any of these drugs can shorten the clinical latency of classical antidepressants