Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.

Habituation of male sexual arousal: effects of attentional focus

Three experiments are reported demonstrating that levels of penile tumescence and subjective sexual arousal are greater when men employ participant-oriented rather than spectator-oriented attentional focus while viewing an erotic film segment. Under each instructional set, there was a reduction in sexual arousal during repeated erotic stimulation. As sexual arousal habituated, the men reported feeling less absorbed during erotic stimulation. When these associated changes in attentional focus (absorption) were partialled out through analysis of covariance, sexual arousal remained relatively stable over trials, suggesting that sexual arousal is less likely to habituate if attentional focus remains constant during repeated erotic stimulation. Further directions for studying associations between habituation of sexual arousal and cognitive processing are discussed.

Circumcision in Australia : further evidence on its effects on sexual health and wellbeing

Objective: To report on the prevalence and demographic variation in circumcision in Australia and examine sexual health outcomes in comparison with earlier research.
Methods: A representative household sample of 4,290 Australian men aged 16–64 years completed a computer-assisted telephone interview including questions on circumcision status, demographic variables, reported lifetime experience of selected sexually transmissible infections (STIs), experience of sexual difficulties in the previous 12 months, masturbation, and sexual practices at last heterosexual encounter.
Results: More than half the men (58%) were circumcised. Circumcision was less common (33%) among men under 30 and more common (66%) among those born in Australia. After adjustment for age and number of partners, circumcision was unrelated to STI history except for non-specific urethritis (higher among circumcised men, OR=2.11, p<0.001) and penile candidiasis (lower among circumcised men, OR=0.49, p<0.001).
Circumcision was unrelated to any of the sexual difficulties we asked about (after adjusting for age) except that circumcised men were somewhat less likely to have worried during sex about whether their bodies looked unattractive (OR=0.77, p=0.04). No association between lack of circumcision and erection difficulties was detected. After correction for age, circumcised men were somewhat more likely to have masturbated alone in the previous 12 months (OR=1.20, p=0.02).
Conclusions: Circumcision appears to have minimal protective effects on sexual health in Australia.

Systemic apomorphine alters HPA axis responses to interleukin-1β adminstration but not sound stress

Apomorphine is a dopamine receptor agonist that was recently licensed for the treatment of erectile dysfunction. However, although sexual activity can be stressful, there has been little investigation into whether treatments for erectile dysfunction affect stress responses. We have examined whether a single dose of apomorphine, sufficient to produce penile erections (50 μg/kg, i.a.), can alter basal or stress-induced plasma ACTH levels, or activity of central pathways thought to control the hypothalamic-pituitary-adrenal axis in rats. An immune challenge (interleukin-1β, 1 μg/kg, i.a.) was used as a physical stressor while sound stress (100 dB white noise, 30 min) was used as a psychological stressor. Intravascular administration of apomorphine had no effect on basal ACTH levels but did substantially increase the number of Fos-positive amygdala and nucleus tractus solitarius catecholamine cells. Administration of apomorphine prior to immune challenge augmented the normal ACTH response to this stressor at 90 min and there was a corresponding increase in the number of Fos-positive paraventricular nucleus corticotropin-releasing factor cells, paraventricular nucleus oxytocin cells and nucleus tractus solitarius catecholamine cells. However, apomorphine treatment did not alter ACTH or Fos responses to sound stress. These data suggest that erection-inducing levels of apomorphine interfere with hypothalamic-pituitary-adrenal axis inhibitory feedback mechanisms in response to a physical stressor, but have no effect on the response to a psychological stressor. Consequently, it is likely that apomorphine acts on a hypothalamic-pituitary-adrenal axis control pathway that is unique to physical stressors. A candidate for this site of action is the nucleus tractus solitarius catecholamine cell population and, in particular, A2 noradrenergic neurons.