NLRP1 promotes tumor growth by enhancing inflammasome activation and suppressing apoptosis in metastatic melanoma.

Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1ß (IL-1ß)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), caspase-1 activation by another danger-signaling sensor NLRP1 does not require ASC because NLRP1 contains a C-terminal CARD domain that facilitates direct caspase-1 activation via CARD-CARD interaction. We hypothesized that NLRP1 has additional biological activities besides IL-1ß maturation and investigated its role in melanoma tumorigenesis. NLRP1 expression in melanoma was confirmed by analysis of 216 melanoma tumors and 13 human melanoma cell lines. Unlike monocytic THP-1 cells with prominent nuclear localization of NLRP1, melanoma cells expressed NLRP1 mainly in the cytoplasm. Knocking down NLRP1 revealed a tumor-promoting property of NLRP1 both in vitro and in vivo. Mechanistic studies showed that caspase-1 activity, IL-1ß production, IL-1ß secretion and nuclear factor-kB activity were reduced by knocking down of NLRP1 in human metastatic melanoma cell lines 1205Lu and HS294T, indicating that NLRP1 inflammasomes are active in metastatic melanoma. However, unlike previous reports showing that NLRP1 enhances pyroptosis in macrophages, NLRP1 in melanoma behaved differently in the context of cell death. Knocking down NLRP1 increased caspase-2, -9 and -3/7 activities and promoted apoptosis in human melanoma cells. Immunoprecipitation revealed interaction of NLRP1 with CARD-containing caspase-2 and -9, whereas NLRP3 lacking a CARD motif did not interact with the caspases. Consistent with these findings, NLRP1 activation but not NLRP3 activation reduced caspase-2, -9 and -3/7 activities and provided protection against apoptosis in human melanoma cells, suggesting a suppressive role of NLRP1 in caspase-3/7 activation and apoptosis via interaction with caspase-2 and -9. In summary, we showed that NLRP1 promotes melanoma growth by enhancing inflammasome activation and suppressing apoptotic pathways. Our study demonstrates a tumor-promoting role of NLRP1 in cancer cells.

[Predictors of sexual behavior in a group of heterosexual university students at risk for AIDS in Montreal]. / Prédicteurs des comportements sexuels à risque face au SIDA chez un groupe d'étudiants universitaires hétérosexuels de Montréal.

In order to evaluate the predictors of risky sexual behavior and AIDS, 573 male and female college students enrolled in French speaking universities in Montreal answered a questionnaire dealing with their sexual behaviors, from which an index of risks was computed (CASH). The analyses show that the best predictors of the CASH for men are associated to their sexual partner taking the pill, peer attitudes toward sexuality and individual sensation-seeking index. For women the best predictors of risky sexual behaviors are the perception of chances to catch AIDS, use of drugs or alcohol during coital behavior, peer group attitudes, personal sexual attitudes and using the pill as a contraceptive. These results suggest that risky sexual behaviors depend on complex processes associated to lifestyle and personality structures.

Use of intravenous alfentanil-midazolam anesthesia for sedation during brief endourologic procedures.

Traditionally, general or regional anesthesia has been employed during endourologic procedures. The success of sedative-analgesic sedation during SWL prompted an investigation into its use in minor endourologic procedures. We compared intravenous alfentanil-midazolam anesthesia (n = 30) with spinal anesthesia (n = 35) during procedures such as ureteroscopy and stent placement using physiologic measures and patient and anesthetist ratings. The former series was prospective; the latter was retrospective. Physiologic measures remained stable and oxygen saturation was above 90% in all patients in both groups during the procedures. The average anesthesia and recovery room times were significantly shorter for patients given alfentanilmidazolam: 23.3 v 36.1 minutes and 85.5 v 179.6 minutes, respectively (P < 0.001; t-test), and this difference reduced the anesthesia cost an average of 46%. The anesthetists rated the intravenous regimen satisfactory in 92% of the patients, and 94% of the patients rated the procedure as comfortable. All 18 of the patients who had previously had spinal anesthesia considered alfentanil-midazolam superior. Intravenous alfentanil-midazolam sedation anesthesia can provide adequate analgesia for many minor endourologic procedures while shortening the anesthesia recovery time.

[Risky sex and contraception in students in France, Quebec and Spain]. / Sexualité à risque et contraception chez des étudiants de France, du Québec et d'Espagne.

In the context of a transational study, 404 sexual active 17-21 years-old students living in Lyon (France), Montreal (Quebec) and Salamanque and Madrid (Spain) have answered a questionnaire dealing with their contraceptive patterns, their perceptions of AIDS and their risky sexual behaviors. Results show that each group uses a different contraceptive strategy. In France and in Quebec those who had their first intercourse before 17 years of age used oral contraceptive rather than the condom. As for AIDS girls from Quebec had a higher index of risky sexual behaviors (CASH) than French, but the opposite was true among boys, while both girls and boys from Spain adopted safer sexual behaviors. Multiple regression analysis shows that the CASH rests on different predictors according to each national context.

[Unsafe sex and contraception among students from France, Quebec and Spain]. / Sexualite a risque et contraception chez des etudiants de France, du Quebec et d'Espagne.

PIP: 404 sexually active, unmarried students aged 17 through 21 from Spain, Quebec, and France were surveyed between 1989 and 1991 concerning their contraceptive usage, knowledge of AIDS, and possible risk factors in their sexual behavior. Prevention of AIDS among young people is a public health priority because relatively liberal sexual attitudes, failure to use condoms, multiple partners, and obliviousness to danger place many young people at risk. 24.6% of the students were 17, 60.5% were 18 or 19, and 14.9% were 20 or 21 years old. 62.1% of respondents from Quebec stated they always used contraception, compared to 37.6% from France and 39.3% from Spain. The proportions reporting usage of specific methods over the past year in France, Quebec, and Spain, respectively, were 21.5%, 15.6%, and 14.0% for rhythm; 35.0%, 29.4%, and 40.0% for withdrawal; 54.1%, 37.5%, and 69.6% for condom; 5.0%, 7.1%, and 5.5% for vaginal spermicides; 8.1%, 1.1%, and 9.3% for diaphragm, IUD, and cervical cap; and 62.1%, 83.5%, and 14.5% for oral contraceptives (OCs). Age at first intercourse was the only personal characteristic studied that was associated with choice of method. Respondents from Spain expressed a significantly greater fear of contracting AIDS than did those from Quebec, while the difference between Spanish and French respondents was not statistically significant. But most respondents in all countries considered their actual risk to be small. A coefficient of hazardous sexual activity was developed to assess the risk behavior of each respondent over the past six months. The measure was based on assigned values of infectivity of various practices. The total score for each respondent varied from 1 to 164, with 164 representing maximum risk. The average coefficients of hazardous sexual activity for males and females, respectively, were 64.4 and 42.2 for French, 59.1 and 69.3 for Canadian, and 32.1 and 32.7 for Spanish respondents. The coefficients were significantly lower in Spain than in the other two countries for almost all factors studied. They were usually higher in Canada than in France. Multiple regression analysis indicated that the coefficient was associated with different predictors in each of the three countries. Interventions intended to prevent AIDS should therefore take into account general social factors as well as norms of sexual behavior in each specific national context.^ieng

[Sexual attitudes and scenarios among students in France, Quebec, and Spain]. / Attitudes et scénarios sexuels d'étudiants de France, du Québec et d'Espagne.

Sexual behaviors and attitudes were surveyed among 787, 17-21 years-old students in Lyon (France), Montreal (Quebec) and Salamanque and Madrid (Spain). Near 55% have had intercourse and oral sex in France, while this was the case of almost 80% in Quebec and only about 30% in Spain. Students from France and Quebec were younger at first intercourse, have had more sexual partners, and higher frequencies of intercourse and oral sex than those from Spain. Girls from Quebec have shown higher sexual permissiveness than other girls. Spanish students, particularly girls, consider their parents' sexual attitudes as far less permissive. Religiosity and church attendance seem to still put a strong damper, in Spain, on young people's sexual behaviors.

[Contraception and adolescents, Rhone-Alpes, 1990]. / La contraception et les adolescents, Rhone-Alpes 1990.

PIP: 173 male and 181 female students of a secondary school in the region of Lyons, France, answered a questionnaire in late 1989 on their sexual and contraceptive attitudes and behavior. 76% of the respondents were French, 8% were Algerian, 3% were Portuguese, and the remainder were from various other countries. 16% were 16 years old or less, 32% were 17, 43% were 18-20, and 9% were 20 or over. Only 1 respondent was married. 49.2% were sexually active and their 1st sexual relations occurred on average at 15-16 years of age. Males reported earlier and more frequent sexual activity than females. In the previous year, 47.7% of sexually active respondents reported that they or their partners had used oral contraceptives, 33.3% condoms, .4% withdrawal, 21.3% rhythm, 5.6% spermicides, and 1% diaphragm. 33.6% reported using contraception regularly, 54.5% sporadically, and 11.9% never. Males were significantly less likely to report use of the more effective methods. Effective contraception was not significantly correlated with age of the respondents, age at 1st sexual experience, the sexual experience of friends, the number of partners, or the frequency of intercourse. Neither was there a correlation between effective contraception and the degree of religiosity, sexual permissiveness, or egalitarian attitudes. Attitudes of parents were correlated significantly though weakly with effective use of contraception. Age was significantly correlated with use of condoms, as were use by friends and approval of partners. The principal sources of information were peers for 50% and parents for 35%. Effective use of contraception and use of condoms appeared to be determined by somewhat different social factors, a finding of relevance for AIDS prevention programs.^ieng

Homophobia and attitudes about AIDS.

A random sample of 407 French Canadian adults responded to a questionnaire about perception of AIDS. Negative attitudes about AIDS are better predicted by homophobia than other measures as are attitudes about extramarital relations and attitudes abut adolescent heterosexuality.

[Not Available]. / L'anxiété face à la mort au Québec : résultats d'un sondage d'opinion.

The results of a poll on the attitudes towards death of a representative sample of the Quebec population are presented. The Templer Scale on death anxiety was employed. These results indicate that death is not a preoccupation which triggers a high degree of tension in Quebec society. However, education level, salary, religions belief, age and sex influence the distribution of responses. Moreover, this anxiety is tied to the non-permissiveness in relation to sexuality as well as to sexism.