Development of 3D-QSAR and pharmacophoric models to design new anti-Trypanosoma cruzi agents based on 2-aryloxynaphthoquinone scaffold.

In this work we have collected a set of 30 trypanosomicidal naphthoquinones and developed pharmacophoric and 3D-QSAR models as tools for the design of new potential anti-Chagasic compounds. Firstly, qualitative information was obtained from SAR and pharmacophoric models identifying some fragments around the 2-aryloxynaphthoquinone scaffold important for the antiparasitic activity. Then, 3D-QSAR CoMFA and CoMSIA models were developed. The models showed adequate statistical parameters where the steric, electrostatic, and hydrophobic features explain the trypanosomicidal effect. Therefore, to validate our models, we carried out the design, synthesis, and biological evaluation on T. cruzi epimastigotes of five new compounds (33a-e). According to CoMFA model, three out of five compounds showed pIC50 values within one logarithmic unit of deviation. The two compounds that did not fit the predictions were those with high lipophilicity, which agreed with the SAR and pharmacophore models. Docking and molecular dynamic studies were performed on T. cruzi trypanothione reductase, in a proposed binding site for this type of naphthoquinone. Interestingly, 33a-e showed the same interaction pattern as a naphthoquinone inhibitor (2). Finally, predicted drug-likeness properties indicated that 33a-e have optimal oral bioavailability. Thus, this study provides new in silico models for obtaining novel trypanosomicidal compounds.

Economic risk factors for HIV infection among women in rural Haiti: implications for HIV prevention policies and programs in resource-poor settings.

AIMS: The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population. METHODS: Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%. RESULTS: In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection. CONCLUSIONS: Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.

[Vaccines: producers in countries of the Southern hemisphere]. / Vaccins: les producteurs des pays du sud.

Vaccine producers in southern hemisphere countries now contribute significantly to global output. In 2006 southern hemisphere countries accounted for more than 10% of the total worldwide production with a progression approximately 70% greater than all producers combined in the two-year period between 2004 and 2006. Though difficult to measure, production in volume is higher due to lower prices practiced in most of these countries. For many years before the 1980s, production was scattered among numerous limited-scale companies. Most were founded at the initiative of governments striving to cover the needs of the population for essential vaccines. A number of institutions and private structures such as Institut Pasteur Production, Connaught Laboratories, and Institut Merieux have also set up production facilities. Today's producers can be divided into two categories, i.e., local producers that produce mainly monovalent vaccines and worldwide producers with strong R&D investment programs. Local producers are located mainly in large southern hemisphere countries such as China, India, Brazil, and Indonesia as well as in eastern countries. For the most dynamic companies, international development is focused on southern hemisphere countries excluding North America and Europe. With the support international organization such as WHO, UNICEF and GAVI, alliances are now being formed and networks are being organized in an effort to ensure reliable supplies of high quality vaccines at affordable prices in developing countries. The contribution of these producers will increase for the greater benefit of the people living in the southern hemisphere.

Fertility traits in spring-calving Aberdeen Angus cattle. 2. Model comparison.

The aim of this study was to investigate the possible superiority of a threshold-linear (TL) approach for calving day (CD) and calving success (CS) analysis in beef cattle over 2 multiple-trait (MT), censored models, considering CD at the first 3 calving opportunities. The CD observations on animals that failed to calve in the latter models were defined as cows being assigned a penalty value of 21 d beyond the last observed CD record within contemporary group (PEN model) or censored CD values that were randomly obtained from a truncated normal distribution (CEN-model). In the TL model, CD records were treated as missing if a cow failed to calve, and parameters were estimated in a TL analysis including CS traits (TLMISS-model). The models included the effects of contemporary group (herd x year of calving x mating management), age at calving, physiological status at mating (lactating or nonlactating cow), animal additive genetic effects, and residual. Field data included 6,763 calving records obtained from first, second, and third parities of 3,442 spring-calving Uruguayan Aberdeen Angus cows. Models were contrasted using a data splitting technique, analyzing correlations between predicted breeding values (PBV) for each pair of subsamples, by rank correlations between PBV obtained with the different models, and by inspecting percentage of sires selected in common using the different approaches at 10 and 25% hypothetical percentages of animals selected. Breeding value correlations of CD between the subsamples for the TLMISS approach were greater (0.67 to 0.68) than correlations for the censored MT models (0.49 to 0.54). Average correlations between PBV of CD in 1 subsample obtained by CEN (PEN, TLMISS) and PBV of CS in the other subsample were -0.53 (-0.55, -0.60) in the first calving opportunity (CO), -0.54 (-0.58, -0.63) in the second CO, and -0.50 (-0.49, -0.58) in the third CO. Rank correlations between PBV for CD in PEN and CEN were high (0.93 to 0.97), but correlations of either method with PBV of CD in TLMISS ranged from 0.50 to 0.71. Common identification of bulls for the top 10% of sires (25% of sires), when selected with PEN/CEN models or the TLMISS model, varied between 50 (44%) and 60 (52%). The use of the TL animal model for genetic evaluation seems attractive for genetic evaluation of fertility traits in beef cattle.

Fertility traits in spring-calving Aberdeen Angus cattle. 1. Model development and genetic parameters.

Calving records (n = 6,763) obtained from first, second, and third parities of 3,442 spring-calving, Uruguayan Aberdeen Angus cows were used to estimate heritabilities and genetic correlations for the linear trait calving day (CD) and the binary trait calving success (CS), using models that considered CD and CS at 3 calving opportunities as separate traits. Three approaches were defined to handle the CD observations on animals that failed to calve: 1) the cows were assigned a penalty value of 21 d beyond the last observed CD record within contemporary group (PEN); 2) the censored CD values were randomly obtained from a truncated normal distribution (CEN); and 3) the CD records were treated as missing, and the parameters were estimated in a joint threshold-linear analysis including CS traits (TLMISS). The models included the effects of contemporary group (herd x year of calving x mating management), age at calving (3 levels), physiological status at mating (nonlactating or lactating), animal additive genetic effects, and residual. Estimates of heritability for CD traits in the PEN and CEN data sets ranged from 0.20 to 0.31, with greater values in the first calving opportunity. Genetic correlations were positive and medium to high in magnitude, 0.57 to 0.59 in the PEN data set and 0.38 to 0.91 in the CEN data set. In the TLMISS data set, heritabilities ranged from 0.19 to 0.23 for CD and 0.37 to 0.42 for CS. Genetic correlations between CD traits varied between 0.82 and 0.88; between CS traits, genetic correlations varied between 0.56 and 0.80. Negative (genetically favorable), medium to high genetic correlations (-0.54 to -0.91) were estimated between CD and CS traits, suggesting that CD could be used as an indicator trait for CS. Data recording must improve in quality for practical applications in genetic evaluation for fertility traits.

Identification of chlamydia and gonorrhoea among women in rural Haiti: maximising access to treatment in a resource poor setting.

OBJECTIVE: To develop a risk assessment algorithm that will increase the identification and treatment of women with cervical infection in rural Haiti. METHODS: Study participants were randomly selected from new patients who accessed services at a women's health clinic in rural Haiti between June 1999 and December 2002. This case-control study included women who tested positive for chlamydia and/or gonorrhoea based on the Gen-Probe PACE 2 laboratory test as cases. Controls were women who tested negative for both of these infections. RESULTS: Women from this area of rural Haiti had a limited level of education and lived in impoverished housing conditions. The sensitivity estimates of Haitian Ministry of Health and WHO algorithms for detecting chlamydia and/or gonorrhoea were generally low (ranging from 16.1% to 68.1%) in this population. Risk scores based on logistic regression models of local risk factors for chlamydia and gonorrhoea were developed and sensitivity estimates were higher for algorithms based on these risk scores (up to 98.8%); however, specificity was compromised. CONCLUSIONS: A risk assessment algorithm to identify women with chlamydia and/or gonorrhoea is more sensitive and less specific than the syndromic management approach advocated by WHO and adapted by the Haitian Ministry of Health. Using a risk assessment tool with high sensitivity based on local risk factors of cervical infection will maximise access to care, improve outcomes, and decrease morbidity in women who have cervical infection in rural Haiti.

Factors associated with forced sex among women accessing health services in rural Haiti: implications for the prevention of HIV infection and other sexually transmitted diseases.

The goals of the current study were to: (1) estimate the prevalence of forced sex among women accessing services at a women's health clinic in rural Haiti; and (2) examine factors associated with forced sex in this population. Based on data from a case-control study of risk factors for sexually transmitted diseases (STDs), a cross-sectional analysis to examine factors associated with forced sex was performed. A number of factors related to gender inequality/socioeconomic vulnerability placed women in rural Haiti at higher risk of forced sex. The strongest factors associated with forced sex in multivariate analyses were: age, length of time in a relationship, occupation of the woman's partner, STD-related symptoms, and factors demonstrating economic vulnerability. The findings suggest that prevention efforts must go beyond provision of information and education to the pursuit of broader initiatives at both local and national levels. At the community level, policy-makers should consider advancing economic opportunities for women who are vulnerable to forced sex. Improving access to community-based income-generating activities may begin to address this problem. However, the viability of these local projects depends largely upon Haiti's 'macro-economic' situation. In order to ensure the success of local initiatives, external humanitarian and development assistance to Haiti should be supported. By broadening the definition of "prevention" interventions, we may begin to address the systemic problems that contribute to the occurrence of forced sex and the increasing incidence of HIV infection throughout the world, such as gender inequality and economic vulnerability. Taking into account factors influencing risk at the local level as well as the macro-level will potentially improve our capacity to reduce the risk of forced sex and the spread of STDs, including HIV infection, for millions of women living in poverty worldwide.

Prevalence and risk factors of STDs in rural Haiti: implications for policy and programming in resource-poor settings.

The goals of the current study are to: (1) estimate the prevalence of sexually transmitted diseases (STDs) among women accessing services at a women's health clinic in rural Haiti; and (2) identify risk factors for STDs in this setting. The design is a case control study, comparing risk factors for women who demonstrated positive laboratory results for chlamydia and/or gonorrhoea to women who tested negative for both of these pathogens. The strongest risk factors for chlamydia and/or gonorrhoea were largely economic variables, with work as a domestic servant increasing the risk by four-fold. Working as a market vendor reduced a woman's risk of having an STD by approximately 45%. Given that economic factors are strongly associated with STD risk in this context, one potential mechanism for reducing the risk of STDs, including HIV, would involve increasing economic opportunities for women in rural Haiti.

Investigation of genotype x country interactions for growth traits in beef cattle.

The importance of genotype x country interactions for weaning and birth weight and postweaning gain between Argentina (AR), Canada (CA), Uruguay (UY), and the United States (US) for populations of Hereford cattle was investigated. Three sample data sets of computationally manageable sizes were formed for each trait and pairwise combination of countries to investigate possible interactions. Parameters were estimated for each sample data set via an accelerated EM-REML algorithm and multiple-trait animal models that considered either weaning or birth weight as a different trait in each country. Direct and maternal (in parentheses) weaning weight genetic correlation estimates for AR-CA, AR-UY, AR-US, CA-UY, CA-US, and UY-US were 0.82 (0.80), 0.81 (0.72), 0.81 (0.79), 0.83 (0.78), 0.85 (0.82), and 0.86 (0.81), respectively. Direct and maternal (in parentheses) birth weight genetic correlation estimates were 0.92 (0.62), 0.97, (0.85), and 0.99 (0.97) for AR-CA, AR-US, and CA-US, respectively. Birth weight was not analyzed for UY due to small amounts of data. Postweaning gain in CA and US was 160-d gain, and in AR and UY 345-d gain was used. Across-country direct genetic correlations for postweaning gain were estimated for each pairwise country data set using a model that considered weaning weight as the same trait across each country, whereas postweaning gain was treated as a different trait in each country. Direct genetic correlation estimates for postweaning gain for AR-CA, AR-UY, AR-US, CA-UY, CA-US, and US-UY were 0.64, 0.80, 0.51, 0.84, 0.92, and 0.83, respectively. The overall results indicate that weaning and birth weights of Hereford calves can be analyzed as the same trait in all countries with a common set of heritabilities and genetic correlations, after adjustment for heterogenous phenotypic variances across countries. Postweaning gain in CA and US can be considered as the same trait and analyzed using a single set of parameters. Postweaning gain in AR and UY should be considered as a separate trait from postweaning gain in CA and US, and postweaning gain in AR and UY can be considered as the same trait and analyzed using a common heritability, after adjustment for phenotypic variance differences between the two countries.

Investigation of genotype x environment interactions for weaning weight for Herefords in three countries.

The objective of this study was to investigate the possibility of genotype x environment interactions for weaning weight (WWT) between different regions of the United States (US) and between Canada (CA), Uruguay (UY), and US for populations of Hereford cattle. Original data were composed of 487,661, 102,986, and 2,322,722 edited weaning weight records from CA, UY, and US, respectively. A total of 359 sires were identified as having progeny across all three countries; 240 of them had at least one progeny with a record in each environment. The data sets within each country were reduced by retaining records from herds with more than 500 WWT records, with an average contemporary group size of greater than nine animals, and that contained WWT records from progeny or maternal grand-progeny of the across-country sires. Data sets within each country were further reduced by randomly selecting among remaining herds. Four regions within US were defined: Upper Plains (UP), Cornbelt (CB), South (S), and Gulf Coast (GC). Similar sampling criteria and common international sires were used to form the within-US regional data sets. A pairwise analysis was done between countries and regions within US (UP-CB vs S-GC, UP vs CB, and S vs GC) for the estimation of (co)variance components and genetic correlation between environments. An accelerated EM-REML algorithm and a multiple-trait animal model that considered WWT as a different trait in each environment were used to estimate parameters in each pairwise analysis. Direct and maternal (in parentheses) estimated genetic correlations for CA vs UY, CA vs US, US vs UY, UP-CB vs S-GC, UP vs CB, and S vs GC were .88 (.84), .86 (.82), .90 (.85), .88 (.87), .88 (.84), and .87 (.85), respectively. The general absence of genotype x country interactions observed in this study, together with a prior study that showed the similarity of genetic and environmental parameters across the three countries, strongly indicates that a joint WWT genetic evaluation for Hereford cattle could be conducted using a model that treated the information from CA, UY, and US as a single population using single population-wide genetic parameters.

Variance and covariance components for weaning weight for Herefords in three countries.

Records from the Hereford Associations of the United States (USA), Canada, and Uruguay were used to estimate genetic and phenotypic variances and covariances for weaning weight. Estimation was done using a complete animal model, relatively large data sets, and the same methodology for the three countries in order to determine whether genetic parameters for weaning weight were homogeneous across environments. Data were composed of 2,322,722, 487,661, and 102,986 edited weaning weight records for USA, Canada, and Uruguay, respectively. Ten samples were obtained from each country by eliminating data from small herds with fewer than 500 records, selecting herds at random from the entire data set after removing the small herds, and then retaining the direct-sire-connected contemporary groups within each sample. The final sample sizes ranged from 9,832 to 46,377 records. An accelerated EM-REML algorithm was used in estimating the (co)variance components in each sample. The estimates were pooled by calculating the arithmetic mean of the 10 samples from within each country. Direct and maternal (in parentheses) heritability estimates were .24 (.16), .20 (.16), and .23 (.18) for USA, Canada, and Uruguay, respectively. Maternal heritabilities reported here are nearly 50% smaller than the values currently used in national genetic evaluation for the breed, which were estimated using sire-maternal grandsire models. Covariance between direct and maternal was negative in all countries, accounting for 6, 8, and 10% of the total phenotypic variation, and the total dam effect was 32.5, 37.0, and 34.0% in USA, Canada, and Uruguay, respectively. Total heritabilities were similar among the countries, with values of .19, .19, and .17 for the three respective countries. The similarity of genetic and environmental parameters across the three countries suggests that joint genetic evaluation is feasible across environments provided that the genotype x environment interaction is negligible and can be ignored.

The results framework--an innovative tool for program planning and evaluation.

This article constitutes a case study of the development and implementation of the "results framework," an innovative planning and evaluation tool that is rapidly becoming a standard requirement for United States Agency for International Development (USAID) projects. The framework is used in a USAID-funded regional initiative for HIV/AIDS prevention in Central America. This new program evaluation and monitoring tool provides many advantages over traditional evaluation approaches that use outside consultants to provide midterm and end-of-project evaluations. The results-framework process, which spans the life of the project, provides an opportunity for program staff, donors, partners, and evaluators to work as a team to collect and use rich, longitudinal data for project planning, implementation, and evaluation purposes.

The effect of sex education on teenagers in St. Kitts and Nevis.

Knowledge of sexual matters is one of several key factors capable of influencing teenage reproductive behavior. This article reports the results of initial and followup surveys designed to test such knowledge among adolescent students in St. Kitts and Nevis before and after they received a family life/sex education course in the mid-1980s. This course provided information about fundamentals of human reproduction and contraception, human growth and development, emotional development, and issues of adolescent sexuality.

Sexual practices among the quiché-speaking mayan population of guatemala.

The purpose of this focus group research was to learn more about the sexual behaviors and practices of this population, in part to better understand their resistance to family planning. The Mayan population is made up of some twenty-three linguistically distinct groups, which collectively constitute 37-42 percent of the Guatemalan population. The largest of these groups, the Quiché- speakers, were the focus of the first phase of this research, reported in this article. Years of economic and social subjugation have resulted in a far lower standard of living among the Mayans than the dominant ethnic group in Guatemala, the Ladinos. This difference is reflected in numerous health indicators, including one of the lowest contraceptive prevalence rates in the hemisphere.A total of thirteen groups were conducted among men and women of different age groups. All groups were organized and moderated by a team of five Mayan field workers who spoke the language and were familiar with the culture of the area. While there was initial hesitation to the idea of discussing the highly sensitive topic of sexual behavior in a group setting, the methodology proved appropriate and yielded detailed data on the subject. All sessions were taped, translated to Spanish and transcribed for purposes of analysis.

[Is female sterilization voluntary in El Salvador]?]. / Es voluntaria la esterilizacion de la mujer en El Salvador?

PIP: Sexual sterilization has become an increasingly important family planning method in developing countries, and notably so in Latin America, but some controversy has surrounded the practice because of the suggestion that individuals are coerced into undergoing sterilization. With the goal of examining allegations that low-income women in El Salvador are sterilized without their full knowledge or consent in family planning programs financed by the US, researchers interviewed 648 women who had received the operation in one of 7 facilities in El Salvador. In general, women were interviewed 1 month after their operation, by 6 trained female interviewers, with the assurance that the follow-up effort was not in any way connected with the facility performing the operation. An effort to sample approximately the same number of women from each facility was not entirely successful because of access difficulties. Most interviewees had been sterilized at below 30 years of age (average age at sterilization was 28 years), had begun having children in adolescence, and had not received more than a primary education. They had an average of 3.4 children and 1/3 had experienced the death of at least 1 child. The response to the survey indicated that female sterilization in El Salvador is voluntary. Women were shown to be aware of other contraception options. They had found out about sterilization and had become further informed about the method through providers and through communications with other women who had known about the operation at least 3 years before making a decision to submit to it, and many had waited between 1 month and 1 year before/between the decision and the actual operation. Only 1 women claimed to have felt pressured to be sterilized, identifying her mother as the source of the pressure.^ieng

Nitrate reduction activity in a continuous flow-through system in marine sediments.

Nitrate reduction in a non-polluted, coastal marine sediment was measured with an open flow-through system. The recorded rates depended upon nitrate concentration but were largely independent of the weight of sediment (14-35 g) and the dilution rate (0.7-5 h(-1)). Rate of nitrate uptake followed classical Michaelis-Menten kinetics, and km and Vmax values were equal to 78µM and 0.168µm mol g(-1) hour(-1), respectively. These values are in good agreement with those found by the other authors for the same biotope but by different methods. This technique of the open flow-through system is fast, simple, and inexpensive and involves small quantities of sediment (∼10 g).

[Brazil: agricultural modernisation and food production restructuring in the international crisis]. / Bresil: modernisation agricole et restructuration alimentaire dans la crise internationale.

PIP: This study examines the complex relationship of capital accumulation, external debt, and food supply in Brazil, a country which has simultaneously increased its food exports and its unsatisfied demand for food imports in the context of the world economic crisis. In Brazil, the substitution of export cash crops for subsistence crops has been accompanied by a profound but incomplete restructuring of the basic food supply and model of consumption, a restructuring made possible by declining real cost of the new foods. The gap between the extremely rapid evolution of consumption, especially in the urban areas, and the possibilities of concomitant transformation of production is the characteristic feature of the change occuring in Brazil. The current diet of the developed countries evolved over a relatively long period and was based on the declining real cost of basic foodstuffs made possible by increasing labor productivity. Between 1800-1900, the real cost of a kilo of bread was halved, while that of meat remained stable. In France and the US respectively, 80 and 90% of the principal cereals are consumed by animals, while in developing countries most grains are directly consumed. Numerous indices suggest that Brazil has begun to differentiate its food regime in the direction of decreased consumption of cereals, tubers, and legumes, and increased consumption of animal products, with grains increasingly consumed indirectly by animals. Since the early 1970s, Brazil has developed a powerful processed food industry which supports intensive breeding of poultry and, to a lesser extent, pork and milk cattle. However, low income population groups have been forced to reduce their consumption of traditional foodstuffs, whose real prices have undergone relative increases, without achieving a satisfactory level of consumption of the new products. Brazilian food problems result not from insufficient production of food but from the choice of a strongly internationalist model of development in the mid-1960s which required insertion into the world economy, notably through a search for new export sectors. The agricultural sector was assigned 3 functions: producing food as cheaply as possible, increasing the proportion of exportable crops, and substituting some of the foods imported. Brazil evolved in 2 decades from a classic agroexporter to a more complex structure reflecting the semiindustrialized state of the economy. The share of processed agricultural goods increased accordingly. The foods produced for the internal market have been changing at the same time that a new hierarchy of exportable products has evolved. Agricultural policy involved recourse to market mechanisms and cheap credit focused on the south and southeastern regions, large and medium sized producers, and a few products including soy, coffee, sugar cane, and cotton. Just 3% of credits went to the traditional foodstuffs beans and manioc. The most serious consequence of the internationalization of the agricultural economy has been a dangerous increase in the vulnerability of low income groups to world food price fluctuations.^ieng

Upper airway lesions in children after accidental ingestion of caustic substances.

Of 33 children admitted within 24 hours after accidental ingestion of a caustic substance, 14 (42.5%) had evidence of upper airway lesions on direct laryngoscopy. Three patients, 10 to 12 months old, needed endotracheal intubation for acute respiratory obstruction; four patients younger than 2 years had severe dyspnea without obstruction; seven patients had mild or no respiratory symptoms. All were discharged without respiratory sequelae, although esophageal stenosis developed in six patients. Nine of 13 patients younger than 2 years, compared to five of 20 patients older than 2 years, had upper airway lesions (P less than 0.01). The frequency of respiratory tract lesions was higher in patients with severe esophagitis. Eleven of 17 patients with severe esophagitis, compared to three of 16 with mild inflammation, had respiratory tract lesions (P less than 0.025). No specific caustic substance predisposed to upper airway lesions.

Public opinion on and potential demand for vasectomy in semi-rural Guatemala.

In this study of 1,600 men aged 25-50 from semi-rural Guatemala, three-fourths had heard of vasectomy. Among these, 54 per cent approved of it. However, the survey reveals a widespread lack of knowledge regarding the procedure, as well as negative perceptions or doubts about its effect on sexual performance, ability to do hard work, health, and manhood. One-fourth of the respondents who knew of vasectomy and who desired no more children expressed interest in having the operation, a finding which raises questions as to the potential (unrecognized) demand for vasectomy in other developing countries.