The role of feelings of intimacy on perceptions of risk for a sexually transmitted disease and condom use in the sexual relationships of adolescent African-American females.

OBJECTIVES: A core construct targeted by behavioural interventions is the perception that one is at risk for acquiring a sexually transmitted disease (STD). The objective of this analysis was to examine the role of intimacy on perceptions of risk for an STD (PRSTD) and condom use within late adolescent females' main relationships. METHODS: A clinical sample of African-American women aged 14-19 years at enrolment were followed prospectively for 3 years. At each semiannual interview, participants reported their partner-specific PRSTD, feelings of intimacy, perceptions of partner's concurrency and condom use at last sex for each of their main sex partners. RESULTS: A total of 285 individuals reported 724 main relationships. Using generalised estimating equations, intimacy was negatively associated with risk perception, after adjusting for perceptions of partner concurrency (OR: 0.68; 95% CI 0.60 to 0.76). PRSTD was no longer associated with condom use after adjusting for intimacy (OR: 1.30; 95% CI 0.83 to 2.02. CONCLUSIONS: Intimacy was found to be associated with risk perception and condom use within adolescent main relationships. Adolescents may not view their intimate partners as sources of infection. The success of individual-level STD prevention efforts, such as condom promotion, might be limited as condoms may be in conflict with adolescents' expectations about intimate relationships.

Emergency contraceptive use as a marker of future risky sex, pregnancy, and sexually transmitted infection.

OBJECTIVE: The objective of the study was to examine whether emergency contraceptive use predicts future sex at risk for pregnancy, pregnancy, or sexually transmitted infection among young women. STUDY DESIGN: A secondary analysis of control group participants (n = 718) from a recent trial of advanced provision of emergency contraception was conducted. RESULTS: We found no association between use of emergency contraception and either pregnancy or infection. Recent use predicted decreased occurrence of subsequent sex at risk for pregnancy among women with a history of sexually transmitted infection (relative risk [RR], 0.39; 95% confidence interval [CI], 0.15-0.97), whereas ever having used predicted increased occurrence among women who either were highly effective method users (RR, 1.45; 95% CI, 1.05-2.01) or had no history of sexually transmitted infection (RR, 1.31; 95% CI, 1.04-1.65). CONCLUSION: Information about prior emergency contraceptive use was not a useful predictor of subsequent pregnancy, infection, or sex at risk for pregnancy among these young women.

Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption.

Disaccharide intolerance I or congenital sucrase-isomaltase deficiency (CSID) is a disorder leading to maldigestion of disaccharides, which is autosomal recessively inherited. Here we analyzed the sucrase-isomaltase (SI) gene from 11 patients of Hungarian origin with congenital sucrase-isomaltase deficiency. Variants in the SI gene had previously been described in CSID patients, which cause amino acid exchanges that affect the transport, the processing, or the function of the SI protein. None of our patients had known mutations for CSID. Our analyses revealed 43 SI variants in total, 15 within exons and one at a splice site. Eight of the exonic mutations lead to amino acid exchanges, causing hypomorph or null alleles. One new variation affects a splice site, which is also predicted to result in a null allele. All potential pathological alterations were present on one allele only. In six out of the 11 patients the phenotype of CSID could be explained by compound heterozygosity.

Joint effects of alcohol consumption and high-risk sexual behavior on HIV seroconversion among men who have sex with men.

OBJECTIVE: To estimate the effects of alcohol consumption and number of unprotected receptive anal intercourse partners on HIV seroconversion while appropriately accounting for time-varying confounding. DESIGN: Prospective cohort of 3725 HIV-seronegative men in the Multicenter AIDS Cohort Study between 1984 and 2008. METHODS: Marginal structural models were used to estimate the joint effects of alcohol consumption and number of unprotected receptive anal intercourse partners on HIV seroconversion. RESULTS: Baseline self-reported alcohol consumption was a median 8  drinks/week (quartiles: 2, 16), and 30% of participants reported multiple unprotected receptive anal intercourse partners in the prior 2 years. Five hundred and twenty-nine HIV seroconversions occurred over 35 ,870 person-years of follow-up. After accounting for several measured confounders using a joint marginal structural Cox proportional hazards model, the hazard ratio for seroconversion associated with moderate drinking (1-14 drinks/week) compared with abstention was 1.10 [95% confidence limits: 0.78, 1.54] and for heavy drinking (>14 drinks/week) was 1.61 (95% confidence limits: 1.12, 2.29) (P for trend <0.001). The hazard ratios for heavy drinking compared with abstention for participants with 0-1 or more than 1 unprotected receptive anal intercourse partner were 1.37 (95% confidence limits: 0.88, 2.16) and 1.96 (95% confidence limits: 1.03, 3.72), respectively (P for interaction = 0.42). CONCLUSION: These findings suggest that alcohol interventions to reduce heavy drinking among men who have sex with men should be integrated into existing HIV prevention activities.

Effects of time-varying exposures adjusting for time-varying confounders: the case of alcohol consumption and risk of incident human immunodeficiency virus infection.

OBJECTIVE: Discuss issues related to time-varying exposures using as an example the recently meta-analyzed literature (Baliunas et al. in Int J Public Health, 2009) on alcohol consumption and risk of HIV infection. METHODS: Cataloged sources of bias and imprecision in the context of time-varying exposures. RESULTS: Confounding, selection, or measurement bias may occur when standard regression approaches are used to estimate effects of time-varying exposures. The reviewed literature on alcohol consumption and HIV infection suffer from one or more of these biases. CONCLUSIONS: Detailed prospective data and thoughtful implementation of appropriate statistical methods are needed to obtain unbiased estimates of time-varying exposures, such as alcohol consumption.

Determinants of alcohol consumption in HIV-uninfected injection drug users.

We assess the association between time fixed and time varying participant characteristics and subsequent alcohol consumption in 1968 injection drug users (median age 37 years, 28% female, 90% African-American) followed semi-annually from 1988 to 2008. Median alcohol consumption was seven drinks per week at study entry (first and third quartile: 1, 26) with 36% reporting binge drinking. Alcohol consumption and binge drinking decreased over follow-up. Older individuals and women reported consuming fewer drinks per week. Higher typical alcohol consumption was reported by those participants who reported in the prior 6 months: non-injection cocaine use, injection drug use, having one or more sex partners, or among men, a same sex partner. Associations were generally similar for drinks per week and binge drinking. This study demonstrates that in a large urban cohort of persons with a history of injection drug use, risky drug use and sexual risk behavior are associated with subsequent alcohol consumption.

3D geometry-based quantification of colocalizations in multichannel 3D microscopy images of human soft tissue tumors.

We introduce a new model-based approach for automatic quantification of colocalizations in multichannel 3D microscopy images. The approach uses different 3D parametric intensity models in conjunction with a model fitting scheme to localize and quantify subcellular structures with high accuracy. The central idea is to determine colocalizations between different channels based on the estimated geometry of the subcellular structures as well as to differentiate between different types of colocalizations. A statistical analysis was performed to assess the significance of the determined colocalizations. This approach was used to successfully analyze about 500 three-channel 3D microscopy images of human soft tissue tumors and controls.

Bovine prion protein gene (PRNP) promoter polymorphisms modulate PRNP expression and may be responsible for differences in bovine spongiform encephalopathy susceptibility.

The susceptibility of humans to the variant Creutzfeldt-Jakob disease is greatly influenced by polymorphisms within the human prion protein gene (PRNP). Similar genetic differences exist in sheep, in which PRNP polymorphisms modify the susceptibility to scrapie. However, the known coding polymorphisms within the bovine PRNP gene have little or no effect on bovine spongiform encephalopathy (BSE) susceptibility in cattle. We have recently found a tentative association between PRNP promoter polymorphisms and BSE susceptibility in German cattle (Sander, P., Hamann, H., Pfeiffer, I., Wemheuer, W., Brenig, B., Groschup, M., Ziegler, U., Distl, O., and Leeb, T. (2004) Neurogenetics 5, 19-25). A plausible hypothesis explaining this observation could be that the bovine PRNP promoter polymorphisms cause changes in PRNP expression that might be responsible for differences in BSE incubation time and/or BSE susceptibility. To test this hypothesis, we performed a functional promoter analysis of the different bovine PRNP promoter alleles by reporter gene assays in vitro and by measuring PRNP mRNA levels in calves with different PRNP genotypes in vivo. Two variable sites, a 23-bp insertion/deletion (indel) polymorphism containing a RP58-binding site and a 12-bp indel polymorphism containing an SP1-binding site, were investigated. Band shift assays indicated differences in transcription factor binding to the different alleles at the two polymorphisms. Reporter gene assays demonstrated an interaction between the two postulated transcription factors and lower expression levels of the ins/ins allele compared with the del/del allele. The in vivo data revealed substantial individual variation of PRNP expression in different tissues. In intestinal lymph nodes, expression levels differed between the different PRNP genotypes.

Analysis of sequence variability of the bovine prion protein gene (PRNP) in German cattle breeds.

Different alleles of the prion protein gene (PRNP) of human and sheep are known to be associated with varying susceptibilities to transmissible spongiform encephalopathies. However, no polymorphisms in the bovine PRNP gene with an effect on susceptibility to prion diseases have been identified to date. In this study we investigated such polymorphisms in German cattle; 48 healthy animals from six different German cattle breeds and 43 cattle with bovine spongiform encephalopathy (BSE) were analyzed. In contrast to previous studies, all three exons as well as the promoter region of the PRNP gene were investigated. Sequence variants in the bovine PRNP gene could have an impact on the amino acid sequence or the expression level of the prion protein and thus on susceptibility to BSE. We identified a total of 60 polymorphisms in the PRNP gene of German cattle. Of these 60 polymorphisms, 36 were newly identified, whereas 24 of these polymorphisms had been described previously. We did not detect any novel polymorphisms affecting the amino acid sequence of the prion protein. However, we identified a 23-bp insertion/deletion polymorphism in the putative PRNP promoter region that shows a significant association with BSE susceptibility in our animals.