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.

Gender differences in presentation, coronary intervention, and outcomes of 28,985 acute coronary syndrome patients in Victoria, Australia

BACKGROUND: Differences in demographics, presenting characteristics, and treatment of heart disease in women may contribute to adverse outcomes. The purpose of this paper was to describe gender differences in the epidemiology, treatment, and outcomes of all admissions for acute coronary syndrome (ACS) in Victoria that occurred between June 2007 and July 2009. METHODS: We undertook a retrospective cohort study of all patients admitted to Victorian hospitals with a first time diagnosis of ACS. Use of angiograms, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and adverse outcomes (death and/or unplanned readmission) were compared by gender and hierarchical logistic regression models were used to account for confounding variables. RESULTS: Of a total of 28,985 ACS patients, 10,455 (36%) were women. Compared with men, women were older (aged ≥75 years: 54% vs 31%; p < .001), more likely to present with multiple comorbidities (>1 comorbidity: 53% vs 46%; p < .001), and more likely to be diagnosed with non-ST-segment elevation ACS (86% vs 80%; p < .001). Women were less likely to receive coronary interventions (angiogram: adjusted odds ratio [aOR], 0.71; 95% CI, 0.66-0.75; PCI: aOR, 0.73; 95% CI, 0.66-0.80; CABG: aOR, 0.58; 95% CI, 0.53-0.64). Adverse outcomes were similar in women and men after accounting for confounding variables. CONCLUSIONS: Our results show that women in Victoria were less likely to receive coronary interventions after an admission for ACS. Clinicians should be wary of inherent gender bias in decisions to refer patients for angiography.