Identification of potent and selective inhibitors of PKR via virtual screening and traditional design.

Protein Kinase RNA-activated (PKR) inhibition is thought to be relevant for immunology due to the potential to reduce macrophage and dendritic cell responses to bacteria and its signaling downstream of TNFα. PKR is also associated with neuroscience indications such as Alzheimer's disease due to its activation by the double stranded DNA (dsDNA) virus HSV1, a virus suggested to be important in the development of AD. Studies exploring the mechanistic role of PKR with existing tool molecules such as the tricyclic oxindole C16 are clouded by the poor selectivity profile of this ATP-competitive, Type I kinase inhibitor. Type II kinase leads such as the benzothiophene or pyrazolopyrimidine scaffolds from literature are equally poor in their selectivity profiles. As such, it became necessary to identify more potent and selective chemical matter to better understand PKR biology. A dual approach was taken. The first step of the strategy included virtual screening of the AbbVie compound collection. A combination of pharmacophore-based and GPU shape-based screening was pursued to identify selective chemical matter from promiscuous leads. The second step of the strategy followed traditional compound design. This step initiated from a literature lead with PKR cross reactivity. Combined, the two parallel efforts led to identification of more selective leads for investigation of PKR biology.

Unintended pregnancy and sex education in Chile: a behavioural model.

This study analysed factors associated with unintended pregnancy among adolescent and young adult women in Santiago, Chile. Three variations of a behavioural model were developed. Logistic regression showed that the effect of sex education on unintended pregnancy works through the use of contraception. Other significant effects were found for variables reflecting socioeconomic status and a woman's acceptance of her sexuality. The results also suggested that labelling affects measurement of 'unintended' pregnancy.

PIP: Using data from the Santiago Young Adult Reproductive Health Survey on 306 females aged 15-24 years living in greater Santiago in 1988 and having experienced premarital intercourse, the authors model the relationship of sex education and unintended pregnancy using social learning theory which posits that any health behavior is part of a dynamic model in which an individual's behavior is determined by the interaction of personal factors and environmental influences. Three variations of a behavioral model are developed. They found that women who had sex education before first intercourse and used contraception at that intercourse were one-third as likely to have a later unintended pregnancy as those with sex education who did not use contraception at first intercourse. Women who did not have sex education and who did not use contraception at first intercourse, however, were less likely to have an unintended pregnancy than women with no sex education who did use contraception. Across all models, moral ambivalence about premarital sexual activity is related to having an unintended pregnancy, Catholic women are twice as likely to have an unintended pregnancy as non-Catholics, and women from poorer backgrounds are less likely to use contraception and more likely to have early pregnancies. How women define their pregnancies can also affect the measurement of unintended pregnancy. It is important to effectively teach the use of contraceptives to reduce unintended pregnancies among adolescents and young adults who have premarital sexual intercourse.

Premarital sexual activity and contraceptive use in Santiago, Chile.

The Santiago Young Adult Reproductive Health Survey was conducted in 1988 to examine the sexual behavior of and contraceptive use among young adults in Chile. The survey was based on multistage household probability samples of 865 women and 800 men aged 15-24 who were living in Santiago in 1988. Findings show that 35 percent of females and 65 percent of males had had premarital intercourse. Among those who had done so, the median age at first experience was 18.4 years for women and 16.4 years for men. Only 20 percent of females and 19 percent of males used contraceptives at first premarital intercourse. Use of contraceptives increased with age at the time of that event. Fertility data reveal that 70 percent of first births were premaritally conceived, and more than one-third of these were born prior to union. The high rates of premarital and unintended pregnancy among young women and the low prevalence of effective contraceptive use indicate a need for greater emphasis on sex education and family planning services directed at adolescents and unmarried young adults in Santiago.

[Reproductive health survey of young adults in greater Santiago]. / Encuesta de salud reproductiva en adultos jóvenes del Gran Santiago.

In 1988 a survey was carried out in order to obtain information on knowledge about reproduction, sexual activity, attitudes, and use of contraceptive methods among residents between 15 and 24 years of age in Greater Santiago. For this purpose, a multistage, self-weighted, non-replacement probability sample was chosen from the entire Santiago urban area. After 2,898 households were visited, 865 women and 800 men were selected and interviewed. For the interview, a questionnaire with 156 questions was developed; many questions were similar to those included in similar surveys in Brazil and Guatemala. The interviewers were professionals who had received prior training. Although 75% of the interviewees had attended sex education classes, they had erroneous ideas on various basic subjects. Sixty-nine percent of the women interviewed had undergone menarche before attending these classes. In addition, 35.4% of the women and 65.0% of the men had had sexual relations prior to marriage, and less than 20% had used any contraceptive method. More than 60% of the interviewees who had children had conceived them before marrying. These findings point up the necessity of offering sex education classes for children and young people, as well as facilitating their access to family planning services, in order to decrease the number of illegitimate and unwanted children that are born in Chile.

Survey of reproductive health in young adults, greater Santiago, 1988.

This article reports the results of an interview survey with 1,665 residents of Metropolitan Santiago 15-24 years old. The survey, which dealt with various aspects of reproductive health, indicated that the sex education received by 75% of the subjects generally failed to convey an accurate knowledge of the basic concepts of sexuality; that use of contraceptive methods was very limited; that approximately 25% of the 865 women interviewed had been pregnant at some time; and that 40% of all the pregnancies were unplanned. These findings demonstrate a need to begin effective sex education programs and to provide adolescent services commensurate with the circumstances of modern life.

[Reproductive health survey in young adults: sexual experience and use of contraceptives in Santiago, Chile]. / Encuesta de salud reproductiva en adultos jóvenes: experiencia sexual y uso de anticonceptivos en Santiago, Chile.

A self weighted, 2 stage probability sample of households in greater Santiago was obtained to select women and men between 15 and 24 years of age in order to obtain information about knowledge of sexual aspects, sexual activity and use of contraception. 35% of females and 65% of males declared to have had premarital sexual intercourse. Mean age at first premarital coitus was 18 and 16 years for women and men, respectively. Partners were 3.5 years older for females and 2.5 years older for males. A steady boy friend was the most common first sexual partner for females. Only 20% of women and 19% of males used contraception at first coitus. Rhythm, pills and withdrawal were the most commonly used methods. Less than 4 coituses in the 2 months preceding the survey were declared by 75% of subjects. All women declared themselves monogamous; 8% of males acknowledged more than one sexual partner in the last month.

Catholicism and fertility in Puerto Rico.

This paper examines the association between fertility and religious affiliation among Puerto Ricans. Bongaarts' proximate determinants framework is used to compare religious categories on behaviors that directly affect fertility. We found no difference in recent fertility between Catholics and non-Catholics in Puerto Rico (total fertility rate = 2.5). We also found Catholics and non-Catholics to be similar on age at first marriage (23.3 and 23.4 years, respectively), contraceptive use (71 percent and 69 percent of married women currently contracepting), and breast-feeding practices (mean duration of breast-feeding of 4.4 and 4.3 months). Differences were observed between less committed and more committed Catholics in total fertility rate, age at first marriage, and contraceptive use, but these differences were not large and were in the opposite direction from the expected. Our findings support the theory of convergence of Catholic and non-Catholic fertility for the US. Our discrepancy with findings from the National Survey of Family Growth is evidence of the cultural diversity in the US Hispanic population and indicates the importance of disaggregating by ethnicity or national origin when studying this population.

Contraceptive use and the need for family planning in Puerto Rico.

In 1982, 69 percent of Puerto Rican women in union were practicing contraception. Forty-five percent relied on contraceptive sterilization (40 percent, female, and five percent, male), eight percent were using the pill, four percent each, the IUD and the condom, five percent relied on rhythm, and three percent were using other methods. Thus, sterilization is the dominant form of fertility regulation in Puerto Rico, and there is relatively little use of reversible methods for childspacing. Reliance on female sterilization peaks among women in union in the age-group 35-44 (54 percent), whereas pill use is highest among those aged 15-24 (approximately 23 percent). Overall, eight percent of all women aged 15-49 are at risk of unintended pregnancy because they are fecund, sexually active, not pregnant or seeking pregnancy and not using any kind of contraceptive method. However, among women in union, this risk ranges from nine percent among those aged 30-39 to 22 percent among women aged 15-19. Reliance on sterilization rather than reversible methods of contraception is strongly influenced by socio-demographic variables. Women with less than a high school education, the wives of blue-collar workers, women living outside of the major cities and those born in Puerto Rico depend upon sterilization more than do women with a college education, the wives of white-collar employees, women living in cities and those born outside of the country. These findings point to the need for improved availability of reversible family planning services, especially for young women, and those whose childbearing is incomplete.

PIP: In 1982, 69% of Puerto Rican women in union were practicing contraception. 45% relied on contraceptive sterilization (40%, female, and 5%, male), 8% were using the pill, 4% each, the IUD and the condom. 5% relied on rhythm, and 3% were using other methods. Thus, sterilization is the dominant form of fertility regulation in Puerto Rico, and there is relatively little use of reversible methods for child spacing. Reliance on female sterilization peaks among women in union in the age-group 35-44 (54%), whereas pill use is highest among those aged 15-24 (approximately 23%). Overall, 8% of all women aged 15-49 are at risk of unintended pregnancy because they are fecund, sexually active, not pregnant or seeking pregnancy and not using any kind of contraceptive method. However, among women in union, this risk ranges from 9% among those aged 30-39 to 22% among women aged 15-19. Reliance on sterilization rather than reversible methods of contraception is strongly influenced by socio-demographic variables. Women with less than a high school education, the wives of blue-collar workers, women living outside of the major cities and those born in Puerto Rico depend upon sterilization more than do women with a college education, the wives of the white-collar employees, women living in cities and those born outside of the country. These findings point to the need for improved availability of reversible planning services, especially for young women, and those whose childbearing is incomplete.

Female migration in Chile: types of moves and socioeconomic characteristics.

This paper examines inter-provincial female migration in Chile for the 1965--1970 period, with a view to describing socioeconomic characteristics of migrant women and to determining differences and similarities in age, educational level, occupation, and type of move (first, return, or repeat) between movers to the capital and to other urban areas. Data are from a five percent sample of the 1970 Chilean census. Findings reveal that non-return migrants to other urban areas are differentiated from those to Santiago by an older age structure, higher educational levels, higher status occupations, and are more likely to be making a second (or higher-order) move. Moreover, educational measures suggest that recent female migration to urban Chile is more prevalent among the upper than the lower strata of the society.