A paradigm for drug discovery employing encoded combinatorial libraries.

Very large combinatorial libraries of small molecules on solid supports can now be synthesized and each library element can be identified after synthesis by using chemical tags. These tag-encoded libraries are potentially useful in drug discovery, and, to test this utility directly, we have targeted carbonic anhydrase (carbonate dehydratase; carbonate hydro-lyase, EC 4.2.1.1) as a model. Two libraries consisting of a total of 7870 members were synthesized, and structure-activity relationships based on the structures predicted by the tags were derived. Subsequently, an active representative of each library was resynthesized (2-[N-(4-sulfamoylbenzoyl)-4'-aminocyclohexanespiro]-4-oxo-7 -hydroxy- 2,3-dihydrobenzopyran and [N-(4-sulfamoylbenzoyl)-L-leucyl]piperidine-3-carboxylic acid) and these compounds were shown to have nanomolar dissociation constants (15 and 4 nM, respectively). In addition, a focused sublibrary of 217 sulfamoylbenzamides was synthesized and revealed a clear, testable structure-activity relationship describing isozyme-selective carbonic anhydrase inhibitors.

O agente comunitário e o usuário de álcool: discursos sobre a concepção e a assistência na Atenção Básica

Estima-se que 52% da população mundial faz uso de álcool, sendo a droga mais consumida no mundo. Ao usuário, o álcool torna-se prejudicial devido às consequências nos níveis biológicos, sociais e funcionais. Assim, a redução do uso abusivo da substância é um dos objetivos da Organização Mundial de Saúde (OMS) e uma das prioridades na agenda de saúde pública mundial. No Brasil, a Política do Ministério da Saúde para a Atenção Integral aos Usuários de Álcool e Outras Drogas teve como objetivo a criação de uma rede de atenção integral a eles - a RAPS (Rede de Atenção Psicossocial). A RAPS é considerada um grande avanço da Reforma Psiquiátrica, já que integra os diversos pontos de atenção disponíveis no Sistema Único de Saúde (SUS). Um dos pontos da RAPS é a Atenção Básica (AB), que através da atuação das equipes da Estratégia Saúde da Família (ESF) tem a possibilidade de monitoração, prevenção do uso e colaboração na reinserção social dos usuários de álcool e outras drogas devido à proximidade e criação de vínculo entre o serviço e usuário. Para que o vínculo seja estabelecido o Agente Comunitário de Saúde (ACS) é a peça fundamental, visto que conhece a comunidade e reconhece suas necessidades, além de ser a figura que medeia as relações entre a equipe de saúde e os usuários. Assim sendo, o objetivo deste estudo foi descrever e analisar o discurso de ACS sobre o uso de álcool e a assistência prestada na AB. Trata-se de um estudo qualitativo de teor descritivo, cuja pesquisa ocorreu em cinco municípios da região central do Estado de Santa Catarina. Foram realizadas entrevistas semiestruturadas, analisadas através do método da Análise de Conteúdo. A análise das entrevistas resultou na formulação de duas categorias e quatro subcategorias empíricas. Os resultados evidenciaram que os ACS percebem o consumo de álcool como inerente a população em virtude da cultura caracterizada pelo consumo habitual e festivo da droga. Eles percebem que o uso do álcool torna-se um problema quanto à definição social atribuída pela comunidade, ressaltando as consequências para a família e outras perdas vivenciadas pelos usuários com base nas repercussões sociais. Quanto à assistência prestada por eles aos usuários de álcool, os resultados indicaram uma prática desprovida de instrumentos ou habilidades para a abordagem adequada do uso, evidenciando uma prática infundada pelos ACS. A prática está pautada também nas crenças em relação aos usuários de álcool, que estão muito ligadas aos estigmas relacionados a estes usuários em geral e não em evidências científicas. Conclui-se que a partir do conhecimento das percepções e práticas deste profissional, é possível direcionar ações que potencialize a prática dos ACS, já que são profissionais com grandes possibilidades de atuação diante da prevenção e tratamento do abuso de álcool e reabilitação social do usuário

Sexual Sensation Seeking, Alcohol Use, and Risky Sexual Behavior Among Men Who Have Sex With Men

Men who have sex with men (MSM) remain most at risk for developing HIV infection. The best prevention in this population is to identify risk factors associated with unprotected sex. Recent research suggests that sexual sensation seeking (SSS) and level of average drinking moderates the relationship between drinking alcohol in the context of sex and risky sexual behavior in a young MSM population (ages 16-20). Current study is an exploratory analysis using multilevel modeling to examine if these results are consistent across a MSM population with a wider range of ages who are also heavy drinkers. Participants (n = 181) included MSM (ages 18-75 years) from a longitudinal clinical research trial. Results indicate that MSM with higher SSS were more likely to have unprotected anal sex if they drank alcohol 3 hours prior to sex than those who did not, (OR = 1.07; 95% CI: 1.03 – 1.12). There was no significant interaction effect for average levels of drinking.

Uso de alcohol y tabaco y variables cognitivo-motivacionales en el ámbito escolar: efectos sobre el rendimiento académico en adolescentes españoles

El objetivo de este estudio fue analizar: (a) la relación entre el consumo de tabaco y alcohol y el rendimiento académico y (b) la capacidad predictiva de los factores psicoeducativos y el abuso de alcohol y tabaco sobre el rendimiento académico en una muestra de 352 adolescentes españoles de 2º a 4º de Educación Secundaria Obligatoria (ESO). Para analizar las variables cognitivo-motivacionales se utilizaron el Self-Description Questionnaire-II, la Sydney Attribution Scale y el Achievement Goal Tendencies Questionnaire. El consumo abusivo de alcohol y tabaco, el sexo y la repetición de curso fueron también evaluados utilizando medidas autoinformadas. El rendimiento académico fue evaluado a partir de los registros escolares. Se utilizaron análisis de frecuencias y regresión logística para analizar los datos. Los análisis de frecuencias revelaron que los estudiantes que abusan del tabaco y el alcohol presentan un rendimiento académico más pobre. Los análisis de regresión logística destacaron que los comportamientos saludables así como las variables educativas y cognitivo-motivacionales ejercieron un efecto predictivo diferente sobre el rendimiento académico dependiendo del área académica analizada. Estos resultados señalan que para mejorar el rendimiento académico en la adolescencia se han de tener en consideración no sólo variables académicas sino también variables relacionadas con la salud.

Influencia de la comunicación publicitaria en el consumo de alcohol

La literatura científica aduce que a mayor exposición de mensajes publicitarios de bebidas alcohólicas, mayor probabilidad de que estas sean consumidas. Método. La muestra constó de 437 estudiantes universitarios. Los objetivos se centraron en analizar la relación entre mensaje publicitario y consumo. Resultados. Existe relación entre publicidad y consumo, dado que el consumo de los jóvenes coincide con el recuerdo de las campañas en cuanto al tipo de bebida consumida. Conclusiones. Observamos que la publicidad parece ser un instrumento de influencia al consumo de alcohol.

Predictive Models of Alcohol Use Based on Attitudes and Individual Values

Two predictive models are developed in this article: the first is designed to predict people's attitudes to alcoholic drinks, while the second sets out to predict the use of alcohol in relation to selected individual values. University students (N = 1,500) were recruited through stratified sampling based on sex and academic discipline. The questionnaire used obtained information on participants' alcohol use, attitudes and personal values. The results show that the attitudes model correctly classifies 76.3% of cases. Likewise, the model for level of alcohol use correctly classifies 82% of cases. According to our results, we can conclude that there are a series of individual values that influence drinking and attitudes to alcohol use, which therefore provides us with a potentially powerful instrument for developing preventive intervention programs.

Predictors and Consequences of Simultaneous Alcohol and Cannabis Use in Adolescents

Background/Aims: The simultaneous use of alcohol and cannabis is common among adolescents, but has been little studied. In this study, we examine predictors and consequences of this behavior in a population-based sample of high school students. Method: Self-reports were obtained from students in Quebec (Canada) followed throughout high school (N=6589). Logistic regressions were used to test the association between individual, family, and peerrelated predictors in grades 7–8 and simultaneous alcohol and cannabis use in grade 10, as well as between simultaneous alcohol and cannabis use in grade 10 and experiencing 3 or more substance-related problems of various types (legal, physical, etc.) in grade 11. Results: Most predictors in grades 7–8 were associated with simultaneous alcohol and cannabis use in grade 10. Only variables reflecting early-onset substance use involvement — alcohol intoxication, cannabis use, and drug use by close friend(s) — remained predictive in a multivariate model. Simultaneous alcohol and cannabis use was associated with increased substance-related problems in grade 11, above and beyond baseline problems and the concurrent use of the two substances in separate episodes in grade 10. Conclusions: Simultaneous alcohol and cannabis use 1) is anticipated by multiple psychosocial risk factors which come together with individual and peer substance use in early high school and 2) is independently predictive of subsequent substance-related problems. Providing adolescents with adequate information regarding the potential harm of simultaneous use may be a useful prevention strategy.

Adolescent Illicit Drug Use and Subsequent Academic and Psychosocial Adjustment : an Examination of Socially-Mediated Pathways

Background: Questions remain regarding the consequences of illicit drug use on adolescent adjustment and the nature of mechanisms that may explain these consequences. In this study, we examined whether early-onset illicit drug use predicts subsequent academic and psychosocial adjustment and whether associations are socially-mediated by decreased school engagement and increased peer deviancy. Method: 4885 adolescents were followed throughout secondary school. We used regressions to determine whether illicit drug use in grade 7 predicted academic achievement, school dropout, depressive symptoms, and conduct problems in grades 10–11, adjusting for potential confounders. We used path analysis to test whether significant associations were mediated by school engagement and peer deviancy in grade 8. Results: Illicit drug use predicted conduct problems and school dropout, but not academic achievement and depressive symptoms. The association between illicit drug use and conduct problems was fully mediated by increased peer deviancy. The association between illicit drug use and school dropout was partially mediated by increased peer deviancy, but remained mostly direct. No indirect association via decreased school engagement was found. Examination of reverse pathways revealed that conduct problems and academic achievement in grade 7 predicted drug use in grades 10–11. These associations were mediated by peer deviancy and school engagement (conduct problems only). Conclusion: Adolescent illicit drug use influences the risk of school dropout and conduct problems in part by contributing to deviant peer affiliation. Reciprocal social mediation characterizes the association between drug use and conduct problems. A reverse mechanism best explains the association with academic achievement.

The pragmatics of computer-mediated communication between South African and Mexican drug traffickers

South Africa and Mexico are ripe with drug trafficking. The gangs and syndicates running the drug businesses in these two countries collaborate occasionally. Communication between these international drug business partners takes place on social media. Their main language of communication is English, mixed with some limited use of Spanish and Afrikaans. The key purpose of the interactions between the South African and Mexican parties is the organisation of their business activities. This study aims at examining how the drug traffickers position each other and themselves regarding their common business interest and how their relationship evolves throughout their interactions. Moreover, it is of interest to look at how these people make use of different social media and their affordances. For this a qualitative analysis of the interaction between two drug traffickers (one South African and one Mexican) on Facebook, Threema and PlayStation 4 was performed. Computer-mediated communication between these two main informants was studied at various stages of their relationship. Results show that at first the interaction between the South African and Mexican drug traffickers consists of interpersonal negotiations of power. The high risk of the drug business and gang/syndicate membership paired with intercultural frictions causes the two interlocutors to be extremely cautious and at the same time to mark their position. As their relationship develops and they gain trust in each other a shift to interpersonal negotiations of solidarity takes place. In these discursive practices diverse linguistic strategies are employed for creating relational effects and for positioning the other and the self. The discursive activities of the interactants are also identity practices. Thus, the two drug traffickers construct identities through these social practices, positioning and their interpersonal relationship.

Predictors and Consequences of Simultaneous Alcohol and Cannabis Use in Adolescents

Background/Aims: The simultaneous use of alcohol and cannabis is common among adolescents, but has been little studied. In this study, we examine predictors and consequences of this behavior in a population-based sample of high school students. Method: Self-reports were obtained from students in Quebec (Canada) followed throughout high school (N=6589). Logistic regressions were used to test the association between individual, family, and peerrelated predictors in grades 7–8 and simultaneous alcohol and cannabis use in grade 10, as well as between simultaneous alcohol and cannabis use in grade 10 and experiencing 3 or more substance-related problems of various types (legal, physical, etc.) in grade 11. Results: Most predictors in grades 7–8 were associated with simultaneous alcohol and cannabis use in grade 10. Only variables reflecting early-onset substance use involvement — alcohol intoxication, cannabis use, and drug use by close friend(s) — remained predictive in a multivariate model. Simultaneous alcohol and cannabis use was associated with increased substance-related problems in grade 11, above and beyond baseline problems and the concurrent use of the two substances in separate episodes in grade 10. Conclusions: Simultaneous alcohol and cannabis use 1) is anticipated by multiple psychosocial risk factors which come together with individual and peer substance use in early high school and 2) is independently predictive of subsequent substance-related problems. Providing adolescents with adequate information regarding the potential harm of simultaneous use may be a useful prevention strategy.

Adolescent Illicit Drug Use and Subsequent Academic and Psychosocial Adjustment : an Examination of Socially-Mediated Pathways

Background: Questions remain regarding the consequences of illicit drug use on adolescent adjustment and the nature of mechanisms that may explain these consequences. In this study, we examined whether early-onset illicit drug use predicts subsequent academic and psychosocial adjustment and whether associations are socially-mediated by decreased school engagement and increased peer deviancy. Method: 4885 adolescents were followed throughout secondary school. We used regressions to determine whether illicit drug use in grade 7 predicted academic achievement, school dropout, depressive symptoms, and conduct problems in grades 10–11, adjusting for potential confounders. We used path analysis to test whether significant associations were mediated by school engagement and peer deviancy in grade 8. Results: Illicit drug use predicted conduct problems and school dropout, but not academic achievement and depressive symptoms. The association between illicit drug use and conduct problems was fully mediated by increased peer deviancy. The association between illicit drug use and school dropout was partially mediated by increased peer deviancy, but remained mostly direct. No indirect association via decreased school engagement was found. Examination of reverse pathways revealed that conduct problems and academic achievement in grade 7 predicted drug use in grades 10–11. These associations were mediated by peer deviancy and school engagement (conduct problems only). Conclusion: Adolescent illicit drug use influences the risk of school dropout and conduct problems in part by contributing to deviant peer affiliation. Reciprocal social mediation characterizes the association between drug use and conduct problems. A reverse mechanism best explains the association with academic achievement.

Methods for integrating alcohol education into existing curriculum. Volume II. Part 7. Final report.

National Highway Traffic Safety Administration, Office of Alcohol Countermeasures, Washington, D.C.

Patterns of currency transactions and their relationship to narcotics traffic : hearing before the Subcommittee on General Oversight and Renegotiation of the Committee on Banking, Finance, and Urban Affairs, House of Representatives, Ninety-sixth Congress, first session on H.R. 5961 ... November 29, 1979.

"Serial no. 96-47."

Sentencing and dispositions of youth DUI and other alcohol offenses: a guide for judges and prosecutors.

Mode of access: Internet.

An Evaluation handbook for health education programs in alcohol and substance abuse /

Mode of access: Internet.