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Type I toxin-antitoxin (TA) systems typically consist of a protein toxin that imbeds in the inner membrane where it can oligomerize and form pores that change membrane permeability, and an RNA antitoxin that interacts directly with toxin mRNA to inhibit its translation. In Escherichia coli, symE/symR is annotated as a type I TA system with a non-canonical toxin. SymE was initially suggested to be an endoribonuclease, but has predicted structural similarity to DNA binding proteins. To better understand SymE function, we used RNA-seq to examine cells ectopically producing it. Although SymE drives major changes in gene expression, we do not find strong evidence of endoribonucleolytic activity. Instead, our biochemical and cell biological studies indicate that SymE binds DNA. We demonstrate that the toxicity of symE overexpression likely stems from its ability to drive severe nucleoid condensation, which disrupts DNA and RNA synthesis and leads to DNA damage, similar to the effects of overproducing the nucleoid-associated protein H-NS. Collectively, our results suggest that SymE represents a new class of nucleoid-associated proteins that is widely distributed in bacteria.

SARS-CoV-2 triggers inflammasome-dependent release of pro-inflammatory cytokine IL-1β and pyroptosis, therefore contributes to the huge inflammatory response observed in severe COVID-19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID-19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID-19 patients, and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID-19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID-19 pathogenesis.

OBJECTIVE To evaluate the factor age at the surgery on long-term postoperative outcomes in patients with postprostatectomy incontinence (PPI) after AdVance XP transobturator male sling implantation. METHODS A total of 115 male patients with PPI, who had undergone AdVance XP sling implantation, were included. Patients had PPI with endoscopically confirmed good sphincteric-contractility and a positive coaptive response. Kruskal-Wallis test with Dunn post-hoc tests were used to analyze the postoperative outcome differences between the patient groups aged less than 66, 66-75, and over greater than 75 years. Outcome measures were the 24 h pad test, the number of daily pads used, the International Consultation on Incontinence Questionnaire short form (ICIQ-SF), International Quality of Life Score (IQOL), Patient Global Impression of Improvement (PGI-I), International Index of Erectile Function-5 (IIEF-5), International Prostate Symptom Score (IPSS), and Visual Analog Scale scores. Observation time points were 3, 6, 12, 24, 36, 48, 60, and 84 months after surgery. RESULTS Between the age groups, there was no difference in the success rate of the procedure (defined as 0 pads/24 h and less than 5 g in the 24-h pad test) at any point in time. Subjective parameters measures using the ICIQ-SF, PGI-I, IQOL, and IPSS scores showed no differences between the two cohorts. Only erectile function (IIEF-5 score) was lower in older patients in comparison to the cohort aged less than 66 years (p

Granulomatous dermatitis (GD) is the most common among a variety of skin reactions that may occur in the varicella‐zoster virus (VZV) reactivation area. It is thought that the formation of granulomas may be the result of a delayed hypersensitivity reaction to viral envelope glycoproteins. Immune checkpoint inhibitors (ICIs), such as nivolumab stimulate T cells and promote hypersensitivity reactions, leading to the formation of granulomas in VZV wrapping proteins, thus triggering VZV‐GD. Few cases of the use of ICIs in patients diagnosed with VZV‐GD have been reported in the literature. Here, we report the clinical case of a patient with metastatic lung cancer which was treated with nivolumab who subsequently developed VZV‐GD. Accurate clinical diagnosis and prompt treatment with antiviral agents have resulted in a complete resolution of the clinical picture. Key points Significant findings Treatment with ICIs may result in VZV reactivation. Accurate differential diagnosis and early treatment led to the resolution of VZV‐GD. What this study adds Few cases of ICI and VZV reactivation have been reported in the literature. Full and timely resolution of VZV‐GD allowed the continuation of ICI treatment.

OBJECTIVE To evaluate the efficacy and safety of the AdVance XP male sling in a midterm follow-up for the treatment of male urinary incontinence in a selected patient cohort. MATERIALS AND METHODS In all, 115 patients with postprostatectomy incontinence were prospectively enrolled. A previous endoscopic evaluation of a sufficient coaptive zone in the repositioning test was mandatory. Patients with urine leakage in supine position or previous incontinence surgery were excluded. Postoperatively a standardized 24-hour pad test and pad usage were evaluated. To compare pre- and postoperative continence status nonparametric t test was used. A P-value of

This trial (20010168) studied how body weight (BW) and body mass index (BMI) influenced the pharmacokinetics (PK) of anakinra. Subjects (n = 32) were assigned to four groups (n = 8) according to BW and BMI. Randomization was according to a four‐treatment, four‐period, four‐sequence crossover design. The four anakinra injections were 100, 150, and 300 mg s.c. and 100 mg i.v. Plasma samples were measured by enzyme‐linked immunosorbent assay and noncompartmental PK parameters estimated. BW demonstrated the following effects: after i.v. administration, significant effects (P 100 kg) obese (BMI > 36) vs. larger (> 100 kg) less obese (BMI

Alcoholism is often associated with other forms of drug abuse, suggesting that innate predisposing factors may confer vulnerability to addiction to diverse substances. However, the neurobiological bases of these factors remain unknown. Here, we have used a combination of imaging, neurochemistry and behavioral techniques to investigate responses to the psychostimulant amphetamine in Marchigian Sardinian (msP) alcohol-preferring rats, a model of vulnerability to alcoholism. Specifically, we employed pharmacological magnetic resonance imaging to investigate the neural circuits engaged by amphetamine challenge, and to relate functional reactivity to neurochemical and behavioral responses. Moreover, we studied self-administration of cocaine in the msP rats. We found stronger functional responses in the extended amygdala, alongside with increased release of dopamine in the nucleus accumbens shell and augmented vertical locomotor activity compared with controls. Wistar and msP rats did not differ in operant cocaine self-administration under short access (2 hours) conditions, but msP rats exhibited a higher propensity to escalate drug intake following long access (6 hours). Our findings suggest that neurobiological and genetic mechanisms that convey vulnerability to excessive alcohol drinking also facilitate the transition from psychostimulants use to abuse.

Triplets of Lactobacullus plantarum strains were isolated from nine contrasting habitats. Without any passage through other culture media, isolation and cultivation were on model media that strictly reproduced the chemical and physical conditions and stressors of the habitats of origin. Here, we demonstrated how L. plantarum regulates and shapes its transcriptome in response to contrasting habitats. Firstly, multivariate clustering analysis of transcriptional data (RNA-Seq), complemented with metabolomics and phenomics, grouped the strains according to the habitats of origin. Subsequently, selected strains from each habitat switched to repeated cultivation on MRS medium and transcriptomes homogenized into a unique cluster. Adaptation to this common medium mainly relied on activation of genes for phage- and prophage-related proteins and transposases. Finally, the comparison of growth across model media and with respect to MRS medium showed that 44% of the overall 3112 gene transcripts changed depending on the specific habitat. Regulation and shaping of transcriptomes mainly concerned carbohydrate acquisition, pyruvate catabolism, proteolytic system and amino acid, lipid and inorganic ion transport and metabolism, with contrasting responses for contrasting habitats. Pathways reconstruction demonstrated how the large genome size of L. plantarum imparts transcriptome and metabolic flexibility as the basic mechanism for a nomadic lifestyle.

Because of the impossibility to consume food of animal origin, vegan consumers are looking for substitutes that could enrich their diet. Among many substitutes, fermented nut products are made from different nut types and obtained after soaking, grinding, and fermentation. Although other fermented vegetable products have been deeply investigated, there are few data about the fermentative processes of nut‐based products and the microbial consortia able to colonize these products are not yet studied. This study characterized a hand‐made vegan product obtained from cashew nut. Lactic acid bacteria responsible for fermentation were identified, revealing a succession of hetero‐ and homo‐fermentative species during process. Successively, some lactic acid bacteria isolates from the home‐made vegan product were used for a pilot‐scale fermentation. The products obtained were characterized and showed features similar to the home‐made one, although the microbiological hazards have been prevented through proper and rapid acidification, enhancing their safety features. Spontaneous fermented products are valuable sources of microorganisms that can be used in many food processes as starter cultures. The lactic acid bacteria isolated in this research can be exploited by industries to develop new foods and therefore to enter new markets. The use of selected starter cultures guarantees good organoleptic characteristics and food safety (no growth of pathogens).

Objectives To evaluate the efficacy and safety of the AdVance XP (R) sling (Boston Scientific, formerly American Medical Systems) in male stress urinary incontinence (SUI) after radical prostatectomy in a prospective multicentre study, as in recent years several studies have shown the effectiveness and safety of the AdVance sling for treating male SUI and in 2010 the second-generation AdVance XP was introduced with several changes in the sling design and a new needle shape. Patients and Methods In all, 115 patients were included. Patients with nocturnal UI, previous UI surgery, previous radiotherapy and a coaptive zone of 50%. All others were classified as failures. Significance analysis was performed using the Wilcoxon test. Results The mean (median) preoperative urine loss in the 24-h pad test was 272.0 (272.0) g. After a follow-up of 3 months (114 patients), 64.9% of the patients were cured and 31.6% had an improved continence status. The mean urine loss decreased significantly to 34.9 g (P < 0.001), with a mean VAS score of 0.5, and mean PGI-I of 1.5. After a follow-up of 24 months (80 patients), 68.8% of the patients were cured and 22.5% had improved. The mean urine loss decreased significantly to 19.1 g (P < 0.001), with a mean VAS score of 0.3, and mean PGI-I of 1.5. After a follow-up of 36 months (47 patients), 66.0% of the patients were cured and 23.4% had improved. The mean urine loss decreased significantly to 21.8 g (P < 0.001), with a mean VAS score of 0.0, and mean PGI-I of 1.6. The mean IQOL and ICIQ-UI SF improved significantly (both P < 0.001) after 36 months. There were no significant postoperative changes in IIEF-5 and IPSS. No intraoperative and no long-term complications occurred. No erosion or explanations occurred. Conclusion The AdVance XP shows good and stable effectiveness and low complication rates even at a mid-term follow-up of up to 36 months.

BACKGROUND The Brazilian exportation of pet food has shown high growth rates in the last two years and determination of the exposure degree is one of the most important parameters for the risk assessment of chemical compounds. In this study the exposure degree of dogs to mycotoxins was estimated and acceptable daily intake (ADI) and safe pet dietary level (SPDL) were calculated. Thus the natural occurrence of fumonisins, zearalenone and aflatoxins was evaluated in 100 dry dog feed samples provided by pet owners in Parana State, Brazil. RESULTS Despite the high frequency of fumonisins (68%), zearalenone (95%) and aflatoxins (68%) in feed samples, the mean levels detected were low. ADI for fumonisins and zearalenone was 20.0 and 1.00 µg kg(-1) body weight (BW) day(-1) respectively and SPDL for fumonisins was 2000 µg kg(-1) feed. The probable daily intake values (1.83 µg fumonisins, 0.93 µg zearalenone and 0.02 µg aflatoxins kg(-1) BW day(-1) ) were low. CONCLUSION The exposure degree of dogs could be assumed to be very low. However, the co-occurrence of these three or other mycotoxins, and possible synergic or additive effects, should be taken into account when determining the maximum allowed levels or risk assessment. © 2016 Society of Chemical Industry.

To use Pharmacokinetic (PK) simulations to illustrate potential differences in clinical outcomes between prophylaxis with conventional recombinant factor VIII (rFVIII) and rFVIIIFc, an extended half-life rFVIII covalently fused to the Fc domain of human IgG1.Population PK estimates from 180 (rFVIIIFc) and 46 (rFVIII) severe haemophilia A patients were used to simulate FVIII activity over time at various rFVIIIFc dosing regimens compared to rFVIII 30 IU kg(-1) three times weekly in a typical adult patient.rFVIII dosed 3x30 IU kg(-1) weekly gave trough levels of 2.7, 2.8 and 0.7 IU dL(-1) , and time spent below 1, 3 and 5 IU dL(-1) of 0.2/1.2/2.3 days week(-1) . rFVIIIFc 2 x 45 IU kg(-1) gave higher troughs (4.4 and 1.7 IU dL(-1) ) and shorter time spent below 1, 3 and 5 IU dL(-1) (0/0.6/1.3 days week(-1) ), with same total factor consumption. rFVIIIFc 2 x 30 IU kg(-1) gave similar troughs (3.0 and 1.2 IU kg(-1) ) and time spent below 1, 3 and 5 IU dL(-1) (0/1.0/2.1 days week(-1) ), despite total factor consumption being reduced by one-third. The same dose and interval of rFVIIIFc (3 x 30 IU kg(-1) ) gave substantially higher troughs (7.8, 8.5 and 3.3 IU dL(-1) ) and markedly shorter time spent below 1, 3 and 5 IU dL(-1) (0/0/0.4 days week(-1) ).The lower clearance of rFVIIIFc compared to conventional rFVIII gives rFVIIIFc the potential of improved bleed prevention and reduced injection frequency at similar factor consumption. Although additional clinical data are required to confirm the conclusions, the simulations clearly show the potential of rFVIIIFc of increased flexibility to tailor treatment to the individual patient, and to advance the standard of care in haemophilia.

Context Stress urinary incontinence (SUI) after radical prostatectomy (RP) continues to be a significant problem with several implications including patient quality of life and other critical postoperative outcomes. Objectives To report the results in terms of efficacy (pad count, 24 hr pad test, QOL questionnaires) and safety (complication rate and type of complications) of all surgical devices approved for the treatment of SUI after RP. Evidence Acquisition A systematic review was conducted in accordance with the PRISMA Statement. A literature search was carried out through the PubMed/Medline, SCOPUS, and Web of Science databases using the keywords "incontinence," "radical prostatectomy," and "'treatment". Inclusion criteria were: number of patients higher than 30, mean follow up longer than 12 months and definition of a successful outcome as the use of 0 to 1 safety pads a day. Evidence Synthesis 113 papers underwent primary review. 51 papers met the inclusion criteria with a total sample size of 4022 patients. Efficacy (0-1 safety pads) was on average 65.7% for AUS, 48.2% for Invance Sling, 48.8% for Advance Sling, 64.2% for ProACT. Twenty four hour pad test and QOL questionnaires were respectively available only in 4 and 18 studies. The overall complication rate was 19.43% for AUS, 7.4% for Invance Sling, 12.3% for Advance Sling, 12.3% for ProACT. Authors' Conclusions Due to the poor overall quality of available studies, it was impossible to identify or refute clinically important differences between the alternative surgical procedures. Although our data seems to suggest that AUS has the highest efficacy in the treatment of SUI following RP it is also associated with the highest complication rate, but this may be due to the longest follow up. Larger rigorous trials are needed in order to support this evidence. Neurourol. Urodynam. 35:875-881, 2016. © 2015 Wiley Periodicals, Inc.

We study a problem of optimal investment/consumption over an innite horizon in a market consisting of two possibly correlated assets: one liquid and one illiquid. The liquid asset is observed and can be traded continuously, while the illiquid one can be traded only at discrete random times corresponding to the jumps of a Poisson process with intensity , is observed at the trading dates, and is partially observed between two dierent trading dates. The problem is a nonstandard mixed discrete/continuous optimal control problem which we face by the dynamic programming approach. When the utility has a general form we prove that the value function is the unique viscosity solution of the HJB equation and, assuming sucient regularity of the value function, we give a verication theorem that describes the optimal investment strategies for the illiquid asset. In the case of power utility, we prove the regularity of the value function needed to apply the verication theorem, providing the complete theoretical solution of the problem. This allows us to perform numerical simulation, so to analyze the impact of time illiquidity in this mixed market and how this impact is aected by the degree

BACKGROUND Due to contamination of the environment by pesticides and their mishandling, there is the need for treatment of contaminated sites and correct disposal of materials containing them. Thus, studies with advanced oxidation processes are expanding and can determine the rate constant of the hydroxyl radical with organic compounds of great importance in environmental contamination. In this context, the use of laser flash photolysis has been shown to be viable for the determination of these constants. RESULTS The reaction rate constants of different pesticides with HO• in degassed acetonitrile have been determined. They were 1.6 × 109 M−1 s−1, 0.6 × 109 M−1 s−1, 1.2 × 109 M−1 s−1, 2.4 × 109 M−1 s−1 and 2.2 × 109 M−1 s−1 for the pesticides carbaryl, propoxur, fenoxycarb, ethoxysulfuron and chlorimuron-ethyl, respectively. These values are about an order of magnitude smaller than the diffusion controlled rate and correlate with the relative rates of disappearance of the pesticides in the photo-Fenton reaction in water. CONCLUSION The correlation of the relative rate constants determined by laser flash photolysis with the relative rates of photo-Fenton degradation of the pesticides is compelling evidence for the participation of the hydroxyl radical in the degradation of these pesticides in the latter system. © 2015 Society of Chemical Industry

This paper describes a theoretical model which takes into account charge injection by thermally stimulated hopping (HP), as proposed by Arkhipov, and Fowler–Nordheim tunneling (FNT), for steady-state response of a metal/organic semiconductor hetero-junction in a polymeric light-emitting diode (PLED). The reason for combining these two models is that both injection processes are usually observed in metal/organic semiconductor hetero-junctions. The present model takes into account the material disorder and the escape probability introduced by Arkhipov et al. for both injection processes. The proposed model was tested with experimental results obtained from a PLED ITO/MEH-PPV/Al. Analysis of the experimental results took into account the well-known characteristic of the MEH-PPV in which the charge transport is dominated by holes. Because of this, the electronic current component is assumed to be negligible compared to that for holes. Considering that the device is composed of two different metal/semiconductor junctions, that is, ITO/MEH-PPV and MEH-PPV/Al, the heights of the different potential barriers could be determined. The injection potential barrier, for holes, was determined as 0.4 eV for direct bias (ITO as anode), and as 0.8 eV for reverse bias (aluminum as anode). It was verified that the FNT process is preferable to the HP process in the following situations: (i) high interface potential barrier, (ii) high electric field, and (iii) low temperatures. On the other hand, that is, for a low interface potential barrier, low electric field and high temperatures, the HP process is dominant. With the application of the proposed model, which combines HP and FNT, it was possible to fit the current versus voltage curves for the studied PLED in a wide range of temperatures and electric fields, for direct and reverse bias. Additionally, it was shown that the condition where the HP injection probability is neglected, the non-linearity in FNT plots, versus , obtained experimentally by several authors, may be a consequence of the material disorder. When the HP process is associated with the FNT a more significant non-linearity in the FNT plot was verified.

Purpose To assess the predictive value of Spectral Domain OCT (SD-OCT) to discriminate between pathological true optic disc edema (ODE) and mimickers responsible for pseudoedema (PODE). Methods We carried out an observational cross-sectional study of subjects consecutively referred from 2011 to 2017 to the Neuro-Ophthalmology service of 4 different hospitals for presumed acute ODE. Among a total of 155 eyes, 95 were identified as ODE and 60 as PODE. Patients underwent the optic nerve OCT evaluation using Zeiss Cirrus Optic Disc Cube 200x200 analysis. Average and four principal quadrants RNFL values were compared between ODE and PODE groups and then with age-matched controls. ROC curve and AUC were calculated to determine optimal cut-off values. Mann-Whitney and chi-square tests were used to compare groups. Statistical correlation was tested by Spearman's rho test. All tests were two sided with p

Red blood cells (RBCs) loaded with iron oxide nanoparticles have been proposed as biomimetic constructs with long half-life (ca. 20 days) in the blood compartment and potentially interesting properties (such as relaxivity) as intravascular contrast agents for magnetic resonance imaging. However, the encapsulation of nanoparticles into RBCs might affect their magnetic properties and relaxivity, which may be significantly different from the native suspension. Here, we present a relaxometric study of P904, a novel ultra small iron oxide nanoparticle developed by Guerbet, enclosed in human RBCs. We measured longitudinal (r1) and transverse (r2) relaxivity over a wide range of Larmor frequencies (0.01–300 MHz) in samples of P904-loaded RBCs, and in control samples with P904 nanoparticles dispersed in blood. Internalization of P904 into RBCs resulted in smaller r1, and in a very high r2/r1 ratio (232) at the highest field. Moreover, a shift of the Curie peak to high fields was observed in P904-loaded RBCs, possibly the result of nanoparticle size selection caused by the internalization process. High r2 relaxivity together with a high r2/r1 ratio and a very long blood half-life make P904-loaded RBCs a promising blood-pool negative contrast agent for MR diagnostic applications. Copyright © 2014 John Wiley & Sons, Ltd.

We isolated Leptospira strains from renal tissue samples of Asiatic red-bellied squirrels Callosciurus erythraeus, captured in Argentina. In December 2008, we captured 34 squirrels in the province of Santa Fe during a short control campaign, which were screened for Leptospira spp. by direct immunofluorescence assays and isolation attempts in renal tissue samples. A prevalence of 38% of Leptospira spp. was obtained by direct immunofluorescence. The isolates, genotyped by the MLVA, were identified as L. interrogans Canicola (N = 2) and L. interrogans Icterohaemorraghiae (N = 1), showing an identical genetic profile to the reference strains Hond Utrech IV (serovar Canicola, serogroup Canicola) and M20 (serovar Copenhageni, serogroup Icterohaemorrhagiae), respectively. Our study shows for the first time that the red-bellied squirrel is a renal carrier of Leptospira interrogans and might act as a reservoir of leptospirosis both in native range and areas of introduction within several European countries, Japan and Argentina. The close association of this introduced squirrel species with humans and domestic animals may increase the probability of disease transmission, particularly in favourable environments. Fil: Gozzi, Ana Cecilia. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina Fil: Guichon, Maria Laura. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación en Biodiversidad y Medioambiente; Argentina Fil: Benitez, Verónica Victoria. Universidad Nacional de Luján. Departamento de Ciencias Básicas; Argentina Fil: Romero, Graciela Noemi. Instituto Nacional de Tecnologia Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Centro de Investigación de Ciencias Veterinarias y Agronomicas; Argentina Fil: Auteri, Carmelo. Instituto Nacional de Tecnologia Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Centro de Investigación de Ciencias Veterinarias y Agronomicas; Argentina Fil: Brihuega, Bibiana. Instituto Nacional de Tecnologia Agropecuaria. Centro Nacional de Investigaciones Agropecuarias. Centro de Investigación de Ciencias Veterinarias y Agronomicas; Argentina

Pharmacological stimulation of N-methyl-D-aspartate receptors (NMDAr) could enhance the outcome of cue-exposure therapy for smoking cessation. NMDAr stimulation can be achieved by increasing pharmacologically the synaptic levels of glycine, a necessary co-agonist. Here, we evaluate the effects of SSR504734, a selective inhibitor of glycine type I transporter (GlyT1) in an extinction-reinstatement procedure inducing robust and lasting nicotine-seeking behavior in rats. Male Wistar rats were trained to associate discriminative stimuli (S(D)s) with the availability of nicotine (0.03 mg/kg/65 μL/2 second/infusion) or sucrose (45-mg pellet) versus non-reward in two-lever operant cages. Reinforced response was followed by cue signaling 20-second time-out (CSs). Once the training criterion was met, rats underwent extinction of lever presses, in the absence of reinforcers, S(D) s and CSs. Re-exposure to nicotine or sucrose S(D+)/CS(+), but not non-reward S(D-)/CS(-), revived responding at the previously reinforced lever. Acute pre-treatment with SSR504734 (10 mg/kg i.p.) reduced nicotine-seeking but not sucrose-seeking behavior without influencing rats' locomotor activity. Sub-chronic treatment (10 mg/kg i.p. for 5 days) during daily exposure to S(D+)/CS(+) reduced nicotine-seeking; however, this effect was transient, with return to S(D+)/CS(+) responding at 72 hours. Full recovery to S(D+)/CS(+) responding was observed after 1 month suggesting that SSR504734 sub-acute treatment did not engage the long-term plasticity mechanisms probably involved in nicotine-seeking. In conclusion, GlyT1-inhibitors might offer a therapeutic opportunity for acute cue-controlled nicotine-seeking, but the lack of persistent effects of the sub-chronic treatment associated with nicotine cues exposure suggests that short-term administration of GlyT1-inhibitor SSR504734 is not sufficient to promote extinction of nicotine-cue conditioned responding.