Knowledge and Attitudes About Sterilization and Long-Acting Reversible Contraception.

OBJECTIVES: To describe understanding of the irreversible nature of permanent contraception and knowledge and attitudes about long-acting reversible contraception (LARC) among individuals seeking and not seeking permanent contraception. METHODS: We performed a cross-sectional survey among patients with Medicaid insurance attending an obstetrics and gynecology clinic in [location]. The survey consisted of 20 true/false and Likert questions assessing knowledge and perceptions about permanent contraception and LARC. Sixty-seven participants were needed to detect a small-to-medium Cohen's effect size f2 = 0.20, with 95% power and alpha = 0.05. RESULTS: Ninety potential participants were contacted and 67 were recruited. Forty-three participants desired permanent contraception and 24 did not. Approximately half of all participants were not aware that permanent contraception is irreversible. Participants who desired permanent contraception had lower LARC knowledge scores (62% correct versus 70%, p = 0.042) and more negative perceptions about LARC (54% versus 38%, p = 0.048). Fewer participants desiring permanent contraception identified LARC efficacy as equal to permanent contraception (32% versus 83%, p < 0.01), and fewer would consider using LARC (intrauterine device: 23% versus 58%, p < 0.01; implant: 16% versus 46%, p < 0.01). These differences persisted in multivariable models adjusting for age, gravidity, and parity. CONCLUSIONS FOR PRACTICE: Individuals who desire permanent contraception may not be aware of its permanence, or of equally effective alternatives. They were also found to have more negative perceptions of LARC in our sample. Additional research is needed to understand factors underlying these differences. Counseling practices should be tailored to ensure accurate knowledge about permanent contraception and LARC for all people seeking to avoid pregnancy.

An exploratory, randomized, crossover MRI study of microbicide delivery with the SILCS diaphragm compared to a vaginal applicator.

BACKGROUND: Microbicide gels studied for HIV prevention often are delivered via a single-use vaginal applicator. Using a contraceptive diaphragm such as the SILCS diaphragm for gel delivery could have advantages, including lower cost and additional pregnancy prevention. STUDY DESIGN: We performed an exploratory, nonblinded, randomized, crossover study among healthy, sexually active, nonpregnant women. Using BufferGel, we evaluated three microbicide delivery methods for gel distribution and retention: SILCS single-sided gel delivery, SILCS double-sided gel delivery and a vaginal applicator (without SILCS). Magnetic resonance images were taken at baseline, after gel insertion, and immediately and 6 h after simulated intercourse. Three women completed all gel delivery methods described in this article. RESULTS: Magnetic resonance imaging analysis indicated similar gel spread in the vagina among all three methods. SILCS single-sided gel application resulted in the most consistent longitudinal coverage; SILCS double-sided gel application was the most consistent in the transverse dimension. CONCLUSIONS: Gel coverage was similar with all three methods. These results suggest that the SILCS microbicide delivery system is comparable to vaginal applicators for delivery of gel products intravaginally.

An in vivo replication-important function in the second coding exon of Tat is constrained against mutation despite cytotoxic T lymphocyte selection.

Human and simian immunodeficiency virus (HIV/SIV) Tat proteins are specified by two coding exons. Tat functions in the transcription of primate lentiviruses. A plethora of in vitro data currently suggests that the second coding exon of Tat is largely devoid of function. However, whether the second exon of Tat contributes functionally to viral pathogenesis in vivo remains unknown. To address this question directly, we compared infection of rhesus macaques with an SIV, engineered to express only the first coding exon of Tat (SIVtat1ex), to counterpart infection with wild-type SIVmac239 virus, which expresses the full 2-exon Tat. This comparison showed that the second coding exon of Tat contributes to chronic SIV replication in vivo. Interestingly, in macaques, we observed a cytotoxic T lymphocytes (CTL) response to the second coding exon of Tat, which appears to durably control SIV replication. When SIV mutated in an attempt to escape this second Tat-exon-CTL, the resulting virus was less replicatively fit and failed to populate the host in vivo. Our study provides the first evidence that the second coding exon in Tat embodies an important function for in vivo replication. We suggest the second coding exon of Tat as an example of a functionally constrained "epitope" whose elicited CTL response cannot be escaped by virus mutation without producing a virus that replicates poorly in vivo.

Inhibiting expression of specific genes in mammalian cells with 5' end-mutated U1 small nuclear RNAs targeted to terminal exons of pre-mRNA.

Reducing or eliminating expression of a given gene is likely to require multiple methods to ensure coverage of all of the genes in a given mammalian cell. We and others [Furth, P. A., Choe, W. T., Rex, J. H., Byrne, J. C., and Baker, C. C. (1994) Mol. Cell. Biol. 14, 5278-5289] have previously shown that U1 small nuclear (sn) RNA, both natural or with 5' end mutations, can specifically inhibit reporter gene expression in mammalian cells. This inhibition occurs when the U1 snRNA 5' end base pairs near the polyadenylation signal of the reporter gene's pre-mRNA. This base pairing inhibits poly(A) tail addition, a key, nearly universal step in mRNA biosynthesis, resulting in degradation of the mRNA. Here we demonstrate that expression of endogenous mammalian genes can be efficiently inhibited by transiently or stably expressed 5' end-mutated U1 snRNA. Also, we determine the inhibitory mechanism and establish a set of rules to use this technique and to improve the efficiency of inhibition. Two U1 snRNAs base paired to a single pre-mRNA act synergistically, resulting in up to 700-fold inhibition of the expression of specific reporter genes and 25-fold inhibition of endogenous genes. Surprisingly, distance from the U1 snRNA binding site to the poly(A) signal is not critical for inhibition, instead the U1 snRNA must be targeted to the terminal exon of the pre-mRNA. This could reflect a disruption by the 5' end-mutated U1 snRNA of the definition of the terminal exon as described by the exon definition model.