Five- and six-coordinate nitrosyl hemes have been prepared and their infrared, electron paramagnetic resonance (EPR), and visible-Soret spectra compared with the corresponding spectra for nitrosyl hemoglobin A (Hba-NO) determined both in the presence and the absence of inositol hexaphosphate (IHP). The five- and six-coordinate NO complexes prepared from either dipyridine or pyridine carbonyl protoheme dimethyl ester had N-O stretch bands (nuno) near 1675 and 1625 cm-1, respectively. These frequencies are sensitive to change in solvent (nuno decreased as the dipole moment of the solvent increased) and, with six-coordinate species, to changes in trans ligand. However, these solvent and trans ligand effects were small compared with the difference (ca. 50 cm-11) between five- and six -coordinate species. The nature of the trans ligand affected the relative proportions of the two...

This study examines leading explanations for unsafe sex in light of in-depth interviews with 102 high-risk gay and bisexual men in Toronto to see how well they engage with the social circumstances and reasoning processes of men in their sexual relationships. We argue that there is an inadequate fit between some of the leading explanations and the discursive accounts provided by high risk men themselves. Their accounts focus on unsafe sex occurring as a resolution to condom and erectile difficulties, through momentary lapses and trade offs, out of personal turmoil and depression, and as a byproduct of strategies of disclosure and intuiting safety. This study examines, in particular the circumstances and rationales associated with men who identify their practices as "barebacking." We conclude with recommendations for communicating prevention messages to those most at risk based on the self-understandings of gay and bisexual men who most frequently practice unprotected sex.

IntroductionIdentifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify “optimal” candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada.MethodsBetween November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify “optimal” candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses.ResultsOf 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were “optimal” candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3–2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2–2.3). The proportion of men who were “optimal” candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP.ConclusionsA higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers.

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Ferrous-carbonyl complexes of the soluble Pseudomonas putida cytochrome P-450,,, and a denatured form (P-420) of this enzyme, as well as cytochromes P-450 and P-448 in liver microsomes from rats pretreated with phenobarbital and 3-methylcholanthrene, have been studied by infrared spectroscopy. The FeCO bonding was examined in order to probe the spatial relationship between the dioxygen-and substrate-binding sites and to determine whether the presence of a unique axial ligand bound trans to carbon monoxide could be responsible for the red-shifted Soret absorbance band maximum at 450 nm. The d-camphor(K+)-bound cytochrome P-450,,, yielded a single infrared absorbance band for the heme-bound carbonyl (uc-, 1940 cm-') having a bandwidth a t half-height ( A v l p ) of 13 ern-', while the camphor-free enzyme gave rise to two stretching frequencies of equal area a t 1963 and 1942 cm-' ( A u l / 2 11-12 and 19-21 cm-', respectively). Addition of d-camphor and a monovalent metal ion (K+) to the camphor-free ferrous carbonyl-enzyme converted the infrared spectrum back to that of the original camphor-bound enzyme. The area of the 1940-cm-I band was found to equal that of the combined areas of the 1963-and 1942-cm-l bands. Conversion of the native enzyme to a denatured form (P-420) yielded a w-, 1966 cm-' with A u l p 23 1 nfrared spectroscopy is a powerful technique for probing the oxygen binding site of heme proteins. Carbon monoxide has been the ligand of choice for such studies because the C-0 stretching frequency is much more easily observed in aqueous media than is that of the 0-0 stretching frequency (Maxwell and Caughey, 1978) and because its substitution for 0 2 is assumed to leave the structure of the protein unaltered. The infrared stretching frequency is related to the C-0 bond energy which is very sensitive to differences in both bond type and environment. The present study was initiated to directly probe, by infrared spectroscopy, the dioxygen-binding site of cyto-