“The present study was conducted to clarify the causes of

“The present study was conducted to clarify the causes of recent improvement of outcomes after hepatectomy in patients with hepatitis C (HC)-related hepatocellular carcinoma (HCC).\n\nFrom 1990 to 2006, 323 curative liver resections for HC-HCC were performed in our department. The patients were divided into two groups: early period (1990-1999: n = 221) and the late period (2000-2006:

n = 102). Prognostic factors were determined to clarify the cause of the survival improvement INCB024360 inhibitor in the modern era.\n\nThe overall survival rates for the patients in the early and late periods were 54.9 and 70.3% at 5 years, respectively (P = 0.0005). There was no difference in the recurrence-free survival rates between the two groups, although both survival without recurrence (P = 0.0003) and survival after recurrence (P = 0.0063) were significantly better in the late period than in the early period. Patients with better liver function, patients with interferon AZD9291 cost (IFN) therapy and patients with subsegmentectomy were selected more frequently, and

the incidence of blood transfusion was decreased in the late period below the level recorded in the early period. For recurrent HCC, lipiodolization decreased and local ablation therapy increased in the late period. The independent prognostic factors for overall survival were preoperative serum levels of albumin and alanine aminotransferase, histological liver cirrhosis, tumor size, intrahepatic metastasis, histological grade, blood transfusion, and IFN therapy.\n\nIn HC-HCC, survival was improved in the late period of the present study. Selection of patients with good liver function, no blood transfusion with reduction of blood loss, anti-hepatitis C virus therapy with IFN, and introduction of local ablation therapy for HCC recurrence

may be related to the improved survival.”
“The role of imaging in treatment decision-making for patients with prostate cancer is to characterize the cancer already BKM120 supplier diagnosed on biopsy, to determine tumor location, to assess tumor volume, and to exclude more-extensive disease. MRI is currently the most established imaging modality for this purpose, with the highest sensitivity and specificity for detection and staging of prostate tumors. The development and wider adoption of active surveillance and focal treatment approaches would also benefit from accurate localization of cancer. As such, 3 T MRI and multiparametric approaches are being developed as tools for the localization and staging of prostate cancer. Men wishing to commence or remain on active surveillance might benefit by having larger cancers identified before embarking on this management strategy. MRI might have its greatest role in patients where there is a discrepancy between PSA and biopsy results suggesting a potential missed prostate tumor.”
“The general prevalence and population composition of gastrointestinal and pulmonary helminths of working donkeys were studied.

5 mg/kg but not more than 2 mg/kg) is the only drug potentially u

5 mg/kg but not more than 2 mg/kg) is the only drug potentially used by a trained physician, without the presence CP-868596 order of an anaesthesiologist (Grade A). With these dosages without drug combination, the highest level of security depends largely on the quality of the hospital environment (Grade A). Intramuscular (< 4 mg/kg) is an alternative route, but the recovery time is delayed (Grade B). The optimal management is performed by an anesthesiologist, it is necessary to facilitate access to the operating room for children undergoing this type of procedure

(Professional consensus). Mainly IV ketamine can be used by pediatric intensive care and emergency physicians who currently have medical skills to detect and treat side effects. (C) 2012 Published by selleck screening library Elsevier Masson SAS.”
“A recent molecular phylogeny of the Arid clade of the genus Hemidactylus revealed that the recently described H. saba and two unnamed Hemidactylus species from Sinai, Saudi Arabia and Yemen

form a well-supported monophyletic group within the Arabian radiation of the genus. The name ‘Hemidactylus saba species group’ is suggested for this clade. According to the results of morphological comparisons and the molecular analyses using two mitochondrial (12S and cytb) and four nuclear (cmos, mc1r, rag1, rag2) genes, the name Hemidactylus granosus Heyden, 1827 is resurrected from the synonymy of H. turcicus for the Sinai and Saudi Arabian species. The third species of this group from Yemen is described formally as a new species H. ulii sp. n. The phylogenetic relationships of the members of ‘Hemidactylus saba species group’ are evaluated and the distribution and ecology of individual species are discussed.”
“The combined use

of fluorescence cystoscopy and cross-polarization optical coherence tomography (CP OCT) with quantitative estimation of the OCT signal was assessed in 92 bladder zones. It demonstrated the diagnostic accuracy in detecting superficial selleck kinase inhibitor bladder cancer of 93.6%, sensitivity 96.4%, specificity 92.1%, positive predictive value 87% and negative predictive value 97.9%. Quantitative estimation of OCT signal standard deviation in cross-polarization (CP OCT SD index) makes the visual criteria of CP OCT image assessment more objective. The level of CP OCT SD index for diagnosing superficial bladder cancer, including cancer in situ, was 4.32 dB and lower. When tumor is located on a postoperative scar, CP OCT SD index may be higher than the threshold level of 4.32 dB due to strong scattering and depolarization in scar fibrous tissue. A high inverse correlation was found between CP OCT SD index and the level expressed by p63, Ki-67, p53, CD44v6 markers. ((c) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)”
“A 3D-QSAR/CoMFA was performed for a series of triazine and its spiro derivative based DHFR inhibitors displaying IC50 values ranging from 0.002 to 58.8 mu M.

As noted in a large body of literature, ignoring such departures

As noted in a large body of literature, ignoring such departures could yield bias and lead to wrong conclusions. Different approaches have been developed to tackle these two major problems.

In this paper, we review available methods for dealing with overdispersion and structural zeros within a longitudinal data setting and propose a distribution-free modeling approach to address the limitations of these methods by utilizing a new class of functional response models. We illustrate our selleckchem approach with both simulated and real study data. Copyright (c) 2012 John Wiley & Sons, Ltd.”
“Macrophages, a heterogeneous and ubiquitous cell population representing up to 15% of the cellular content of different types of tissue, are the principal cell mediators in response to pathogens, inflammation process, tissue homeostasis and repair and play a pivotal role in atherosclerosis and insulin resistance because of their capacity to be the major source of inflammatory CX-6258 chemical structure cytokines, which can function through paracrine and endocrine mechanisms.

Recently, differently activated macrophage populations have been described, depending on a large variety of microenvironmental signals, and it is now recognized that their activation plays a crucial role in the development and progression of atherosclerosis. There is good evidence of the ability of conjugated linoleic acids and polyphenolic compounds to modulate inflammation in experimental models involving macrophages. This observation leaves room to the intriguing hypothesis that macrophage polarization Volasertib could represent one of the unifying mechanisms through which specific food components can exert anti-inflammatory effects in humans, contributing to the prevention of chronic diseases strongly linked to inflammation, such as atherosclerosis. Future studies

should be addressed to substantiate this hypothesis, investigating whether or not physiological concentrations of food-derived metabolites can perturb macrophage activation in vitro. On the in vivo side, the evaluation of macrophage populations in tissues, however complex, should be included among the analyses performed in observational and intervention studies, in order to understand if macrophage activation is involved in the anti-inflammatory activity of a specific dietary regimen. (C) 2011 Elsevier B.V. All rights reserved.”
“The diagnosis of pseudohypoparathyroidism type 1a (PHP1a) is challenging, because both the osteodystrophy, such as brachydactyly and round face, and the symptomatic hypocalcemia usually develop beyond infancy. Although ectopic calcification may be an early sign of PHP1a, there are no systematic reviews regarding the time of its appearance. We here report on two PHP1a patients who presented with subcutaneous calcification in neonatal period.

“The tuber of Liriope platyphylla Wang et Tang (Liliaceae)

“The tuber of Liriope platyphylla Wang et Tang (Liliaceae), also known as Liriopis tuber, is famous in Oriental medicine owing to its tonic, antitussive, expectorant and anti-asthmatic properties. In the present study, the effects of Liriopis tuber water extract (LP) on proinflammatory mediators secreted from lipopolysaccharide (LPS)-induced cultured RAW 264.7 mouse macrophages were investigated. Nitric oxide (NO), prostaglandin E2 (PGE2) and intracellular calcium release were measured after 24 h incubation. Various cytokines and nuclear transcription factors (NF-kappa

B and CREB) of LPS-induced RAW 264.7 were measured by a multiplex bead array assay based on xMAP technology. LP (up to 200 mu g/mL) significantly decreased levels of nitric oxide (NO), interleukin (IL)-6, IL-10, IL-12p40, interferon-inducible this website EPZ5676 in vivo protein-10, keratinocyte-derived

chemokine, monocyte chemotactic protein-1, vascular endothelial growth factor, granulocyte macrophage-colony stimulating factor, platelet derived growth factor, PGE2, intracellular calcium, NF-kappa B and CREB in LPS-induced RAW 264.7 cells (p < 0.05). The results suggest that LP has immunomodulatory activity to reduce excessive immune reactions during the activation of macrophages by LPS. Further studies are needed to verify the precise mechanism regulating immunomodulatory activities of LP.”
“Objective: This study’s objective was to determine the effect of therapeutic massage on peripheral blood flow utilizing dynamic infrared thermography in a constant temperature/humidity thermal chamber to assess noncontact skin temperature.\n\nDesign: The design was a repeated-measures crossover experimental design; the independent variable was treatment condition (massage, light touch, control).\n\nSetting: The study setting was a university research laboratory.\n\nSubjects: Seventeen (17) healthy volunteers Crenolanib supplier (8 males/9 females; age

= 23.29 +/- 3.06) took part in the study.\n\nInterventions: One (1) 20-minute neck and shoulder therapeutic massage treatment was performed for each of the three treatment conditions.\n\nOutcome measures: The dependent variable was noncontact, mean skin temperature in 15 regions measured at 6 time points (pretest and 15, 25, 35, 45, and 60 minutes post-test) for each treatment condition.\n\nResults: The massage treatment produced significant elevations in temperature in five regions: anterior upper chest (p – 0.04), posterior neck (p – 0.0006), upper back (p – 0.0005), posterior right arm (p – 0.03), and middle back (p – 0.02). Massage therapy produced significant increases in temperature over time, compared to the other conditions, in the anterior upper chest, and posterior neck, upper back, right arm, and the middle back. Additionally, the temperatures remained above baseline levels after 60 minutes.

“Producers of Bt cotton, Gossypium hirsutum L (Malvaceae)

“Producers of Bt cotton, Gossypium hirsutum L. (Malvaceae), in the southeastern USA face significant losses from highly polyphagous stink bug species. These problems may be exacerbated by crop rotation practices that often BAY 73-4506 mouse result in cotton, peanut, Arachis hypogaea L., and soybean, Glycine max (L.) Merrill (both Fabaceae), growing in close proximity to one another. Because all of these crops are hosts for the major pest stink bug species in the region, we experimentally examined colonization preference of these species among the crops to clarify this aspect of their population dynamics. We

planted peanut, soybean, Bt cotton, and glyphosate-tolerant (RR) non-Bt cotton at three sites over 3 years in replicated plots ranging from 192 to 1 323 m2 and calculated odds ratios for colonization of each crop for Nezara viridula (L.) and Euschistus servus (Say) (both Hemiptera: Pentatomidae). In four of five experiments, both E. servus and N. viridula preferred soybean significantly more often than Vorinostat clinical trial Bt cotton,

non-Bt cotton, and peanut. Neither N. viridula nor E. servus showed any preference between non-Bt and Bt cotton in any experiment. Both species had higher numbers in Bt and non-Bt cotton relative to peanut; this was not significant for any single experiment, but analyses across all experiments indicated that N. viridula preferred Bt and non-Bt cotton significantly more often than peanut. Our results suggest that soybean in the landscape may function as a sink for stink bug populations

relative to nearby peanut and cotton when the soybean is in the reproductive stage of development. Stink bug preference for soybean may reduce pest pressure in near-by crops, but population increases in soybean could lead to this crop functioning as a source for later-season pest pressure in cotton.”
“Nephilid spiders are selleck chemical known for gigantic females and tiny males. Such extreme sexual dimorphism and male-biased sex ratios result in fierce male-male competition for mates. Intense sperm competition may be responsible for behaviors such as mate guarding, mate binding, opportunistic mating, genital mutilation, mating plugs and male castration (eunuchs). We studied the mating biology of two phylogenetically, behaviorally and morphologically distinct south-east Asian nephilid spider species (Herennia multipuncta, Nephila pilipes) in nature and in the laboratory. Specifically, we established the frequencies and effectiveness of plugging (a plug is part of the male copulatory organ), and tested for male and female copulatory organ reuse. Both in nature and in the laboratory, plug frequencies were higher in H. multipuncta (75-80% females plugged) compared with N. pilipes (45-47.4%), but the differences were not significant. Plugs were single and effective (no remating) in H. multipuncta but multiple and ineffective (remating possible) in N. pilipes.

(Int J Periodontics Restorative Dent 2010;30:187-193 )”

(Int J Periodontics Restorative Dent 2010;30:187-193.)”
“Aims: Brown adipose

tissue (BAT) is a potential source of false-positive findings on [(18)F] FDG PET. In this report, we have discussed Liproxstatin-1 supplier the (18)F-FDG uptake mechanisms in BAT and have aimed to determine if dual time point PET imaging helps to differentiate BAT from malignant lesions.\n\nMethods: Patients with dual-time-point PET/CT scans were reviewed retrospectively and 31 cases (11 males, 20 females, age: 28.6 +/- 9.7) having hypermetabolic BAT were included for this study. (18)F-FDG uptake in BAT was quantitatively analyzed by maximum standardized uptake values (SUVmax), and average percent change in SUVmax of BAT between early and delayed images was calculated.\n\nResults: Compared to the initial scans,(18)F-FDG Bafilomycin A1 in vitro uptakes in BAT in delayed images were higher in 26 of the patients, and lower in one patient. In terms of body regions,18F-FDG uptake increased in 80.6%, remained unchanged in 5.5% and decreased in 13.9% of the body regions. Mean percent change in SUVmax, including all BAT regions, was 19.8 +/- 19.1% while the mean percent increase was calculated as 69 +/- 25% in regions where progressive accumulation was observed. The increase in SUVmax correlated with the time interval between the two scans.\n\nConclusion:

Physiologic (18)F-FDG uptake in BAT increases over time and may mimic the behavior of malignant lesions on dual time point PET imaging. Without the exact anatomic definition of the CT scan, false positive interpretation of PET data may be possible in cases with atypical BAT. (C) 2010 Elsevier Espana, S.L. and SEMNIM. All rights reserved.”
“In Arabidopsis thaliana environmental and endogenous cues promote flowering by activating expression of a small

number of integrator genes. The MADS box transcription factor SHORT VEGETATIVE PHASE (SVP) is a critical inhibitor of flowering that directly represses transcription of these genes. However, we show by genetic C59 Wnt manufacturer analysis that the effect of SVP cannot be fully explained by repressing known floral integrator genes. To identify additional SVP functions, we analyzed genome-wide transcriptome data and show that GIBBERELLIN 20 OXIDASE 2, which encodes an enzyme required for biosynthesis of the growth regulator gibberellin (GA), is upregulated in svp mutants. GA is known to promote flowering, and we find that svp mutants contain elevated levels of GA that correlate with GA-related phenotypes such as early flowering and organ elongation. The ga20ox2 mutation suppresses the elevated GA levels and partially suppresses the growth and early flowering phenotypes of svp mutants.

Data were based on 642 patients treated with esophagectomy at 183

Data were based on 642 patients treated with esophagectomy at 183 hospitals between November 1, 2006 and February 28, 2007. Multivariate analysis revealed that postoperative

morbidity and length of stay regressed against hospital and surgeon volumes, patient characteristics, and details of the procedures.\n\nIn a logistic regression model, esophagectomies by surgeons performing a high volume of operations (> 100 cases; “high case-volume surgeons”) were followed by a significantly lower rate of postoperative complications (odds ratio [OR], 0.49; 95% confidence interval (CI), 0.24-0.98, P = 0.04). In a proportional hazard model, high-volume surgeons reduced the length of stay significantly: the hazard ratio for medium casevolume surgeons (50-99 cases) was 1.53 [95% CI, 1.14-2.06, Vorinostat Epigenetics inhibitor P = 0.00], whereas that for the highest case-volume surgeons was 1.34 [95% CI, 1.00-1.79, P = 0.05] Buparlisib in vitro vs the lowest case-volume surgeons. Neither postoperative complications nor length of stay were significantly associated with hospital volume.\n\nThese findings indicate that morbidity after esophagectomy is more dependent on individual surgeon-specific

skill than on hospital-based factors.”
“Recent years have witnessed a new turn in the field of gene expression regulation. Actin and an ever-growing family of actin-associated proteins have been accepted as members of the nuclear crew, regulating eukaryotic gene transcription. In complex with heterogeneous nuclear ribonucleoproteins and certain myosin species, actin has been shown to be an important regulator

in RNA polymerase II transcription. Furthermore, actin-based molecular motors are believed to facilitate RNA polymerase I transcription and possibly downstream events during rRNA biogenesis. Probably these findings represent the tip of the iceberg of a rapidly expanding area within the functional architecture of the cell nucleus. Further studies will contribute to clarify how actin mediates nuclear functions with a glance to cytoplasmic signalling. These discoveries have the potential to define novel regulatory networks required see more to control gene expression at multiple levels.”
“Meditation is used to improve psychological well-being, but there is no scientific quantitative evidence to prove the relation between them. Therefore, in this study, an effective classifier, namely a support vector machine (SVM), is applied to classify meditation experiences and help validate the interaction between emotional stability and a meditation experience. Three groups (10 subjects in each), created based on practice experience in meditation (S group with 10-30 years, J group with 1-7 years, and N group with 0 years of experience in Tibetan Nyingmapa meditation), were recruited to receive visual stimuli in the form of affective pictures. The images shown were selected from the International Affective Pictures System (TAPS), a confidential database.

While some earlier reports show

While some earlier reports show Selleckchem PU-H71 that Berenil possesses trypanolytic and trypanostatic properties, some studies show it may also indirectly affect the host immune system. Our recent extensive studies show that treatment with Berenil reduces pro-inflammatory cytokine (IL-6, IL-12 and TNF) production in macrophages in vivo and in vitro following stimulation with Ttypanosoma congolense, lipopolysaccharide (LPS), unmethylated bacterial CpG motifs and Poly I:C This global effect was not due to downregulation of Toll-like receptor (TLR) expression on innate immune cells. Instead, Berenil significantly downregulated phosphorylation of mitogen activated

protein kinases (MAPKs, including ERK, p38 and JNK),

signal transducer and activator of transcription (STAT) proteins (including STAT1 and STAT3) and NF kappa B p65 subunit, key signaling molecules and transcription factors involved in the production of proinflammatory cytokines. The ability of Berenil to downregulate major intracellular signaling pathways that lead to proinflammatory cytokine production suggests that it could be used to treat conditions caused by excessive production of inflammatory RSL3 mouse cytokines. (C) 2014 Elsevier B.V. All rights reserved.”
“L-asparaginase (L-ASP) is a therapeutic enzyme used clinically for the treatment of childhood acute lymphoblastic leukemia. L-ASP’s anticancer activity is believed to be associated primarily with depletion of asparagine, but secondary glutaminase activity has also been implicated in its anticancer mechanism of action. To investigate the effects of L-ASP on amino acid metabolism, we have developed an LC-MS/MS metabolomics platform for high-throughput quantitation of 29 metabolites, including all 20 proteinogenic amino acids, 6 metabolically related amino Selleck ABT737 acid derivatives (ornithine, citrulline, sarcosine, taurine, hypotaurine, and cystine), and 3 polyamines (putrescince, spermidine, and spermine) in adherent cultured cells. When we examined the response of OVCAR-8 ovarian cancer cells in culture to L-ASP, asparagine

was depleted from the medium within seconds. Interestingly, intracellular asparagine was also depleted rapidly, and the mechanism was suggested to involve rapid export of intracellular asparagine followed by rapid conversion to aspartic acid by L-ASP. We also found that L-ASP-induced cell death was more closely associated with glutamine concentration than with asparagine concentration. Time-course analysis revealed the dynamics of amino acid metabolism after feeding cells with fresh medium. Overall, this study provides new insight into L-ASP’s mechanism of action, and the optimized analytical method can be extended, with only slight modification, to other metabolically active amino acids, related compounds, and a range of cultured cell types.

The assembly of a connectome requires sensitive hardware tools to

The assembly of a connectome requires sensitive hardware tools to measure neuronal and neurovascular features in all three dimensions, as well as software and machine learning for data analysis and visualization. We present the state of the art on the reconstruction of circuits and vasculature that link brain anatomy and function. Analysis at the scale of tens of nanometers yields connections between identified neurons, while analysis at the micrometer scale yields probabilistic rules of connection between neurons and exact vascular connectivity.”
“Objectives To construct a job-exposure matrix (JEM) for an Ohio beryllium processing https://www.selleckchem.com/products/mln-4924.html facility between 1953 and 2006

and to evaluate temporal changes in airborne selleck compound beryllium exposures.\n\nMethods Quantitative area-and breathing-zone-based exposure measurements of airborne beryllium were made between 1953 and 2006 and used by plant personnel to estimate daily weighted average (DWA) exposure concentrations for sampled departments and operations. These DWA measurements were used to create a JEM with 18 exposure metrics, which

was linked to the plant cohort consisting of 18 568 unique job, department and year combinations. The exposure metrics ranged from quantitative metrics (annual arithmetic/geometric average DWA exposures, maximum DWA and peak exposures) to descriptive qualitative metrics (chemical beryllium species and physical form) to qualitative assignment of GSK1904529A cost exposure to other risk factors (yes/no). Twelve collapsed job titles with long-term consistent industrial hygiene samples were evaluated using regression analysis for time trends in DWA estimates.\n\nResults Annual arithmetic mean DWA estimates (overall plant-wide exposures including administration, non-production, and production estimates) for the data by decade ranged from a high of 1.39 mu g/m(3) in the 1950s to a low of 0.33 mu g/m(3) in the 2000s. Of the 12 jobs evaluated for temporal trend, the average arithmetic DWA mean was 2.46 mu g/m(3) and the average

geometric mean DWA was 1.53 mu g/m(3). After the DWA calculations were log-transformed, 11 of the 12 had a statistically significant (p<0.05) decrease in reported exposure over time.\n\nConclusions The constructed JEM successfully differentiated beryllium exposures across jobs and over time. This is the only quantitative JEM containing exposure estimates (average and peak) for the entire plant history.”
“Background: Dyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model.

Although mural invasion alone was rare, the separate reporting of

Although mural invasion alone was rare, the separate reporting of both mural and extramural invasion in patients with stage C tumor is informative and desirable.”
“Background. Plasmodium falciparum

reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite protein essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit parasite growth in vitro, but the relevance of naturally acquired PfRH5-specific antibodies in humans is unclear. Methods. We assessed this website pre-malaria season PfRH5-specific immunoglobulin G (IgG) levels in 357 Malian children and adults who were uninfected with Plasmodium. Subsequent P. falciparum infections were detected by polymerase chain reaction every 2 weeks and malaria

episodes by weekly physical examination and self-referral for 7 months. The primary outcome was time between the first P. falciparum infection and the first febrile malaria episode. PfRH5-specific IgG was assayed for parasite growth-inhibitory activity. Results. The presence of PfRH5-specific IgG at enrollment was associated with a longer time between the first blood-stage PXD101 in vitro infection and the first malaria episode (PfRH5-seropositive median: 71 days, PfRH5-seronegative median: 18 days; P = .001). This association remained significant after adjustment for age and other factors associated with malaria risk/exposure (hazard ratio,

.62; P = .02). Concentrated PfRH5-specific IgG purified from Malians inhibited P. falciparum growth in vitro. Conclusions. Naturally acquired PfRH5-specific IgG inhibits parasite growth in vitro and predicts protection from malaria. These findings strongly support efforts to develop PfRH5 as an urgently needed blood-stage malaria vaccine. Clinical Trials Registration Prexasertib in vitro NCT01322581.”
“Positron emission tomography (PET) has convincingly provided in vivo evidence that psychoactive drugs increase dopamine (DA) levels in human brain, a feature thought critical to their reinforcing properties. Some controversy still exists concerning the role of DA in reinforcing smoking behavior and no study has explored whether smoking increases DA concentrations at the D3 receptor, speculated to have a role in nicotine’s addictive potential. Here, we used PET and [C-11]-(+)-PHNO ([C-11]-(+)-4-propyl-3,4,4a, 5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol) to test the hypothesis that smoking increases DA release (decreases [C-11]-(+)-PHNO binding) in D2-rich striatum and D3-rich extra-striatal regions and is related to craving, withdrawal and smoking behavior. Ten participants underwent [C-11]-(+)-PHNO scans after overnight abstinence and after smoking a cigarette. Motivation to smoke (smoking topography), mood, and craving were recorded.