Preliminary survey on the occurrence of microplastics in bivalve mollusks marketed in Apulian fish markets.

Microplastics (MPs) are a relevant threat to food safety because they are ingested by humans through various foods. Bivalves are at high risk of microplastic contamination due to their filter-feeding mechanism and pose a risk to consumers as they are ingested whole. In this work, microplastics were detected, quantified, identified, and classified in samples of mussels (Mytilus galloprovincialis) and oysters (Crassostrea gigas) marketed in the Apulia region. The total number of plastic debris was 789 particles in the mussel samples and 270 particles in the oyster samples, with size ranging from 10 to 7350 µm. Fragments with size within the category of 5-500 µm were the predominant findings in both species, with blue as the predominant color in mussels and transparent in oysters; most of the debris was polyamide and nylon polymers in the mussels and chlorinated polypropylene in the oysters. These results show that mussel and oyster samples purchased at fish markets are contaminated with microplastics. The sources may be diverse and further studies are needed to assess the impact of the marketing stage on microplastic contamination in bivalves to better define the human risk assessment associated with microplastic exposure from bivalves consumption.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Respiratory pathogens in children with acute lower respiratory infection detected through multiplex real-time PCR / Patógenos respiratorios en niños con infección respiratoria aguda baja detectados mediante PCR multiplex en tiempo real

Abstract Introduction: Acute respiratory infection in children has a high burden of disease. Detection of multiple micro -organisms through molecular testing of nasopharyngeal swab samples could change the paradigm of a single pathogen being the cause of respiratory disease in children and prove its usefulness in clinical practice. Objective: To characterize the pathogens identified in nasopharyngeal swab samples by means of multiplex realtime polymerase chain reaction (RT-PCR), as well as clinical variables and laboratory findings in children <5 years diagnosed with acute lower respiratory tract infection (ALRTI) and hospitalized in Bogotá D.C., Colombia. Materials and methods: Cross-sectional study conducted in 81 children hospitalized between September 2019 and March 2020 at the Clínica Cafam and in whom nasopharyngeal swab samples were collected for microbiological identification using the Allplex™ multiplex RT-PCR assay. Correlations between the number of pathogens and blood cells and C-reactive protein levels were determined by Spearman's rank correlation coefficient. Results: Patients' mean age was 17.23 months (±14.44), 54.32% were males, and 51.85% were young infants. A total of 149 microorganisms (60.40% viruses) were identified in 63 children (77.78%). Mixed infection and coinfection were reported in 48.15% and 11.11% of children, respectively. Regarding clinical findings, shortness of breath, upper airway obstruction, cough, fever and pharyngitis were the most common clinical signs and/or symptoms in patients with mixed infection (32.97%), coinfection (64.40%), mixed infection (29.78%), and absence of microorganism (22.00%), respectively. A negative correlation was observed between the number of leukocytes and the number of neutrophils and the number of microorganisms detected in the preschoolers group (r=-0.46; p =0.058 and r=-0.51; p =0.033, respectively). Furthermore, a positive correlation was found between monocyte count and the number of microorganisms detected (r=0.53; p =0.0096). Conclusion: Multiplex RT-PCR assay allowed the identification of microorganisms in most children, as well as cases of mixed infection and coinfection in more than half of the sample. In addition, clinical findings in these children were highly heterogeneous as per the assay result..

Resumen Introducción. La infección respiratoria aguda en niños tiene una alta carga de enfermedad. La detección de múltiples microorganismos a través de pruebas moleculares en hisopados nasales podría cambiar el paradigma de patógeno único causal de enfermedad respiratoria en niños y ser de utilidad en la práctica clínica. Objetivo. Caracterizar los patógenos identificados mediante la técnica de reacción en cadena de polimerasa multiplex en tiempo real (RT-PCR) en hisopado nasal, así como las variables clínicas y los resultados de laboratorio en niños <5 años diagnosticados con infección respiratoria aguda baja (IRAB) y hospitalizados en Bogotá D.C., Colombia. Materiales y métodos. Estudio transversal realizado en 81 niños hospitalizados entre septiembre de 2019 y marzo de 2020 en la clínica Cafam y en quienes se hizo hisopado nasal para realizar la identificación microbiològica mediante la prueba RT-PCR multiplex Allplex. Las correlaciones entre el número de patógenos y los niveles de células del hemograma y el nivel de proteína C reactiva se determinaron mediante el coeficiente de correlación de Spearman. Resultados. La edad promedio fue 17.23 meses (±14.44), 54.32% fueron varones y 51.85%, lactantes menores. Se identificaron 149 microorganismos (60.40% virus) en 63 niños (77.78%). Hubo infección mixta en el 48.15% y coinfección en 11.11% de los niños. Respecto a los hallazgos clínicos, la dificultad respiratoria, la obstrucción de la vía respiratoria alta, la tos, la fiebre y la faringitis fueron más comunes en los casos de infección mixta (32.97%), ausencia de microorganismo (16.00%), coinfección (64.40%), infección mixta (29.78%) y ausencia de microorganismo (22.00%), respectivamente. Se observó una correlación negativa entre el número de leucocitos y neutrófilos y el número de microorganismos detectados en preescolares (r=-0.46; p=0.058 y r=-0.51; p=0.033) y una positiva entre el recuento de monocitos y el número de microorganismos detectados (r=0.53; p =0.0096). Conclusión. La prueba RT-PCR multiplex permitió identificar microorganismos en la mayoría de niños, así como casos de infección mixta y coinfección en más de la mitad de la muestra. Además, los hallazgos clínicos fueron altamente heterogéneos entre los niños según el resultado de la prueba.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Behavioral and Psychological Strategies of Long-Term Weight Loss Maintainers in a Widely Available Weight Management Program.

OBJECTIVE: The study's purpose was to use validated questionnaires to identify novel behavioral and psychological strategies among weight loss maintainers (WLMs) in a commercial weight management program. METHODS: Participants were 4,786 WLMs in WW (formerly Weight Watchers, New York, New York) who had maintained weight loss ≥ 9.1 kg (24.7 kg/23.8% weight loss on average) for 3.3 years and had a current mean BMI of 27.6 kg/m2 . A control group of 528 weight-stable individuals with obesity had a mean BMI of 38.9 kg/m2 and weight change < 2.3 kg over the previous 5 years. RESULTS: WLMs versus Controls practiced more frequent healthy dietary choices (3.3 vs. 1.9; η p 2 = 0.37), self-monitoring (2.6 vs. 0.7; η p 2 = 0.30), and psychological coping (2.5 vs. 1.1; η p 2 = 0.25) strategies. WLMs also reported more willingness to ignore food cravings (4.4 vs. 3.5; η p 2 = 0.16) and had greater habit strength for healthy eating (5.3 vs. 3.2;  η p 2 = 0.21). Standard canonical coefficients indicated that dietary (0.52), self-monitoring (0.40), and psychological (0.14) strategies as well as habit strength for healthy eating (0.15) contributed independently and most (49.5% of variance) to discriminating groups. CONCLUSIONS: In a widely available weight management program, more frequent practice of healthy dietary, self-monitoring, and psychological coping strategies as well as development of greater habit strength for healthy eating differentiated long-term WLMs from weight-stable individuals with obesity.

Occurrence of Ochratoxin A in the wild boar (Sus scrofa): chemical and histological analysis.

Ochratoxins are fungal secondary metabolites that may contaminate a broad variety of foodstuffs, such as grains, vegetables, coffee, dried fruits, beer, wine and meats. Ochratoxins are nephrotoxins, carcinogens, teratogens and immunotoxins in rats and are also likely to be in humans. In 2009/2010, a survey of the presence of Ochratoxin A (OTA) in regularly hunted wild boars in the Calabria region of southern Italy detected OTA in 23 animals in the kidney, urinary bladder, liver and muscles: 1.1 ± 1.15, 0.6 ± 0.58, 0.5 ± 0.54 and 0.3 ± 0.26 μg/kg, respectively. Twelve tissue samples showed levels of OTA higher than the guideline level (1 μg/kg) established by the Italian Ministry of Health. In five wild boars, gross-microscopic lesions were described for the organs displaying the highest concentrations of OTA determined by HPLC-FLD analysis, i.e., the kidney, liver and urinary bladder.

Positivity for HLA DR1 is associated with basal cell carcinoma in renal transplant patients in southern Brazil.

BACKGROUND: Renal transplant patients have a higher incidence of non-melanoma skin cancer (NMSC). Previous studies hypothesized that human leukocyte antigen (HLA), especially types DR1, DR4, and DR7, may influence the incidence of these tumors. This study investigates the association between NMSC and the presence of HLA DR1, DR4, and DR7 in renal transplant patients in southern Brazil. METHODS: In a historical cohort study, 1032 patients who underwent renal transplantation during the period from January 1993 to December 2006 were examined to identify occurrences of NMSC and HLA status prior to transplant. RESULTS: Of the 1032 patients examined, 59 (5.71%) developed NMSC (squamous cell carcinoma [SCC]: 2.42%; basal cell carcinoma [BCC]: 1.74%; both: 1.55%). The presence of HLA DR1 was associated with a higher probability of developing any NMSC and particularly with developing BCC (P < 0.05). There was no statistically significant association between the presence of HLA DR4 or DR7 and the occurrence of NMSC in this sample. CONCLUSIONS: HLA DR1 appears to be associated with the development of BCC, as well as with the higher number of NMSC lesions in renal transplant patients. This study supports the trend to associate the DR1 allele with BCC and not with SCC.

Chemopreventive efficacy of Atorvastatin against nitrosamine-induced rat bladder cancer: antioxidant, anti-proliferative and anti-inflammatory properties.

To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) CONTROL: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.

HLA and skin cancer.

Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.

HLA and skin cancer / HLA e câncer de pele

Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.

Os cânceres da pele - melanoma e não-melanoma - são neoplasias comuns e com incidência crescente ao longo de décadas. Representam um importante problema de saúde pública. A patogênese destas neoplasias não é completamente compreendida, assim como não o são os fatores genéticos envolvidos. Os genes HLA estão associados a alguns tumores e podem representar um dos mecanismos implicados no desenvolvimento do câncer de pele. Apresenta-se uma revisão atualizada sobre a relação entre antígenos HLA, câncer da pele não-melanoma e melanoma.

A novel recruitment message to increase enrollment into a smoking cessation treatment program: preliminary results from a randomized trial.

Most smokers do not utilize approved interventions for nicotine dependence, reducing the probability of cessation. Smoking cessation programs typically use recruitment messages emphasizing the health threats of smoking. Augmenting this threat message by describing the genetic aspects of nicotine addiction may enhance enrollment into a cessation program. During telephone recruitment, 125 treatment-seeking smokers were randomized to receive by phone either a standard threat message or a threat plus genetic prime message and were offered open-label varenicline and counseling. There was a greater rate of enrollment into the cessation program for the threat plus genetic prime participants (51.7%) versus the threat-only participants (37.7%; p = .03). Smokers who self-identified from racial/ethnic minority groups were less likely to enroll in the cessation program (p = .01) versus smokers who self-identified as Caucasian. These preliminary data suggest that a simple, affordable, and transportable communication approach enhances enrollment of smokers into a smoking cessation program. A larger clinical trial to evaluate a genetic prime message for improving recruitment into smoking cessation programs is warranted.

Association of the nicotine metabolite ratio and CHRNA5/CHRNA3 polymorphisms with smoking rate among treatment-seeking smokers.

INTRODUCTION: Genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in the CHRNA5/A3/B4 gene cluster with heaviness of smoking. The nicotine metabolite ratio (NMR), a measure of the rate of nicotine metabolism, is associated with the number of cigarettes per day (CPD) and likelihood of cessation. We tested the potential interacting effects of these two risk factors on CPD. METHODS: Pretreatment data from three prior clinical trials were pooled for analysis. One thousand and thirty treatment seekers of European ancestry with genotype data for the CHRNA5/A3/B4 SNPs rs578776 and rs1051730 and complete data for NMR and CPD at pretreatment were included. Data for the third SNP, rs16969968, were available for 677 individuals. Linear regression models estimated the main and interacting effects of genotype and NMR on CPD. RESULTS: We confirmed independent associations between the NMR and CPD as well as between the SNPs rs16969968 and rs1051730 and CPD. We did not detect a significant interaction between NMR and any of the SNPs examined. CONCLUSIONS: This study demonstrates the additive and independent association of the NMR and SNPs in the CHRNA5/A3/B4 gene cluster with smoking rate in treatment-seeking smokers.

Nicotine metabolite ratio predicts smoking topography and carcinogen biomarker level.

BACKGROUND: Variability in smoking behavior is partly attributable to heritable individual differences in nicotine clearance rates. This can be assessed as the ratio of the metabolites cotinine and 3'-hydroxycotinine (referred to as the nicotine metabolism ratio; NMR). We hypothesized that faster NMR would be associated with greater cigarette puff volume and higher levels of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a carcinogen biomarker. METHODS: Current smokers (n = 109) smoked one of their preferred brand cigarettes through a smoking topography device and provided specimens for NMR and total NNAL assays. RESULTS: Faster nicotine metabolizers (third and fourth quartiles versus first quartile) based on the NMR exhibited significantly greater total puff volume and total NNAL; the total puff volume by daily cigarette consumption interaction was a significant predictor of total NNAL level. CONCLUSION: A heritable biomarker of nicotine clearance predicts total cigarette puff volume and total NNAL. IMPACT: If validated, the NMR could contribute to smoking risk assessment in epidemiologic studies and potentially in clinical practice.

Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis.

PURPOSE: To evaluate the efficacy of a selective cyclooxygenase-2 (COX-2) inhibitor in rat bladder cancer chemoprevention, as well as to assess the relevance of inflammation, proliferation and oxidative stress in tumor growth and in its prevention. RESULTS: The main findings were: (I) the incidence of carcinoma was: control: 0% (0/8); BBN: 65% (13/20); CEL: 0% (0/8) and BBN + CEL: 12.5% (1/8); (II) the mean tumor volume per rat with tumor and per tumor were significantly lower in the BBN + CEL group (21.2 and 5.3 +/- 0.4 mm(3)) vs. BBN (138.5 +/- 7.5 and 112.5 +/- 6.4 mm(3)); (III) the incidence of pre-neoplasic (hyperplasia and dysplasia) and neoplasic (papillary tumors and carcinoma in situ-CIS) lesions were notoriously reduced in the CEL + BBN treatment; (IV) CEL significantly reduced serum TGFbeta1 and CRP and increase TNFalpha and IL-1beta (p < 0.001); (V) CEL reduced MDA formation in serum (p < 0.001) and liver (p < 0.05) and also showed a trend to reduction in kidney. METHODS: Drug treatments were performed during the first 8 w, followed by 12 w for tumor expression/prevention, in the following groups: control-vehicle; carcinogen-0.05% of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN); celecoxib (CEL)-10 mg/kg/day and preventive CEL + BBN. The bladders were analyzed for number and volume of tumor and nature of urothelium lesions. Serum was assessed for markers of inflammation, proliferation and redox status. CONCLUSIONS: Celecoxib has demonstrated an outstanding inhibitory effect on bladder cancer chemoprevention, which might be due to its expected anti-inflammatory actions, as well as by anti-proliferatory and antioxidant actions. This data supports a pivotal role of cancer chemoprevention strategies based on COX-2 inhibition.

Predictors of enrollment in a smoking cessation clinical trial after eligibility screening.

PURPOSE: A fraction of smokers considered eligible for pharmacotherapy treatment trials for nicotine dependence enrolled. Little is known about smokers not enrolling in a treatment trial or how these smokers differ from those who have enrolled. PROCEDURES: We screened 2257 individuals for a smoking cessation trial involving behavioral counseling and a novel medication. FINDINGS: Of those screened, 33% of callers were eligible for enrollment (N=753). Of those eligible for the trial, 37% attended the subsequent enrollment session (N=282). We compared the 282 attendees to the 471 smokers who were eligible for the trial but did not attend. Logistic regression indicated that African American smokers were about half as likely to enroll in the trial (odds ratio [OR], 0.55; 95% CI, 0.36-0.84); for every year increase in age, participants were 4% more likely to enroll (OR, 1.04; 95% CI, 1.02-1.06); and participants who were motivated to enroll in the trial for financial incentives were 42% less likely to enroll in the trial (OR, 0.58; 95% CI, 0.45-0.76). CONCLUSIONS: These findings suggest the need to devise and test recruitment strategies directed toward African Americans and younger smokers to increase enrollment among eligible smokers to smoking cessation treatment trials.

Evidence for endogenous formation of N'-nitrosonornicotine in some long-term nicotine patch users.

INTRODUCTION: Nitrosation of nicotine or its metabolites in the human body could lead to formation of the 2 carcinogenic tobacco-specific nitrosamines-N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). METHODS: We investigated the possibility of endogenous formation of NNN in people who had stopped smoking and used the 21-mg nicotine patch for 6 months. We quantified urinary biomarkers of exposure to NNN-the sum of NNN and its pyridine-N-glucuronide, referred to as total NNN. Also measured were NNK metabolites-the sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its N- and O-glucuronides, referred to as total NNAL. RESULTS: The average decline of urinary total NNN was less drastic than that of total NNAL: 22% of baseline total NNN and 7.3% of baseline total NNAL were detected in urine 24 weeks after smoking cessation and patch use (p = .02). The average ratio of total NNN to total NNAL in the same urine samples increased from 0.14 in baseline urine to 0.38 after 24 weeks of nicotine patch use. DISCUSSION: Overall, these results demonstrate that endogenous formation of NNN may occur in nicotine patch users. However, the levels of urinary total NNN during patch use were generally extremely low. Moreover, in 10 of 20 subjects analyzed here, the rate of decline in total NNN was similar to that in total NNAL, indicating that endogenous formation of NNN is virtually nonexistent in these subjects. Supplementation with ascorbic acid could be a simple approach to block possible NNN formation in nicotine patch users.

A placebo-controlled trial of modafinil for nicotine dependence.

BACKGROUND: Nicotine deprivation symptoms, including fatigue and attentional deficits, predict relapse following smoking cessation. Modafinil (Provigil), a wakefulness medication shown to have efficacy for the treatment of cocaine addiction, was tested as a novel therapy for nicotine dependence in a double-blind placebo-controlled trial. METHODS: One hundred and fifty-seven treatment-seeking smokers received brief smoking cessation counseling and were randomized to: (1) 8 weeks of modafinil (200mg/day), or (2) 8 weeks of placebo. The primary outcome was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT). Secondary outcomes included cigarette smoking rate and post-quit nicotine deprivation symptoms (e.g., negative affect, withdrawal). RESULTS: In this interim study analysis, EOT quit rates did not differ between treatment arms (42% for placebo vs. 34% for modafinil; OR=0.67 [0.34-1.31], p=0.24). Further, from the target quit date to EOT, the daily smoking rate was 44% higher among non-abstainers in the modafinil arm, compared to non-abstainers in the placebo arm (IRR=1.44, CI95=1.09-1.89, p<0.01). Modafinil-treated participants also reported greater increases in negative affect and withdrawal symptoms, vs. participants randomized to placebo (ps<0.05). CONCLUSIONS: These data do not support the use of modafinil for the treatment of nicotine dependence and, as a consequence, this trial was discontinued. Cigarette smoking should be considered when modafinil is prescribed, particularly among those with psychiatric conditions that have high comorbidity with nicotine dependence.

Genetic variation in mu-opioid-receptor-interacting proteins and smoking cessation in a nicotine replacement therapy trial.

Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy, we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins, namely ARRB2 and HINT1. Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label randomized trial. In a logistic regression model controlling for OPRM1 genotype, treatment type, and other covariates, we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up. Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up, but this may not be a pharmacogenetic effect, given that the participants were drug free during this time. Haplotype analysis did not reveal any significant associations for either gene. We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance; however, interpretation of this finding is limited by the small number of participants with the minor alleles for both genes. Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation, further exploration of opioid pathway genes in larger prospective pharmacogenetic trials may be warranted.

Translating basic science to improve pharmacotherapy for nicotine dependence.

Nicotine dependence has a complex multifactorial etiology, underscoring the value of applying a transdisciplinary research model. The important goal of treating nicotine dependence can be realized by transdisciplinary research that translates discoveries in basic neuroscience, pharmacology, genetics, and behavioral science to develop new treatment models that can be translated readily into the clinic and community. As part of this special issue highlighting work at the Transdisciplinary Tobacco Use Research Centers (TTURCs), we describe transdisciplinary research at the University of Pennsylvania TTURC aimed at elucidating the neurobiological and genetic basis of nicotine dependence, the development of novel medications, and the translation of this research to practice.