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Background: African American/Black and Hispanic persons living with HIV (AABH-PLWH) are under-represented in AIDS clinical trials (ACTs) in the United States. Barriers AABH-PLWH experience to ACTs are multi-faceted, including distrust of medical research, low levels of knowledge, unsupportive social norms, lack of referral, and challenges navigating ACT systems. In past research we found a multi-component peer-driven intervention was efficacious in boosting rates of screening for/enrollment into ACTs. The present qualitative study seeks to understand AABH-PLWH's perspectives on which specific intervention features or components had utility. Interventions features explored included structural elements (e.g., small group sessions, individual sessions on the ACT research unit); approaches (e.g., Motivational Interviewing); and specific components (e.g., small-group discussion of historical and cultural factors reducing participation among AABH-PLWH). Methods: A total of 37 AABH-PLWH (mean age 50.6 years, SD=7.5 years; 48.6% female; 62.2% African American/ Black, 27.0% Hispanic) were purposively selected from a larger study for in-depth interviews, which were audiorecorded, transcribed verbatim, and analyzed using systematic content analysis. Results: We found the intervention improved knowledge and positive attitudes toward ACTs, and triggered sociallevel facilitators such as altruism and more positive social norms. Discussions of cultural/historical barriers to ACTs associated with race/ethnicity had utility. Holding a session on the ACT research unit reduced fear and increased motivation. Results highlighted the value of Motivational Interviewing, and several components were perceived as less useful (e.g., involving social network members in ACT decisions). Conclusion: Findings can inform future intervention designs to address racial/ethnic disparities in ACTs and have implications for trials of other conditions where racial/ethnic disparities persist.

The N-terminal cysteine-rich somatomedin B (SMB) domain (residues 1-44) of the human glycoprotein vitronectin contains the high-affinity binding sites for plasminogen activator inhibitor-1 (PAI-1) and the urokinase receptor (uPAR). We previously showed that the eight cysteine residues of recombinant SMB (rSMB) are organized into four disulfide bonds in a linear uncrossed pattern (Cys(5)-Cys(9), Cys(19)-Cys(21), Cys(25)-Cys(31), and Cys(32)-Cys(39)). In the present study, we use an alternative method to show that this disulfide bond arrangement remains a major preferred one in solution, and we determine the solution structure of the domain using NMR analysis. The solution structure shows that the four disulfide bonds are tightly packed in the center of the domain, replacing the traditional hydrophobic core expected for a globular protein. The few noncysteine hydrophobic side chains form a cluster on the outside of the domain, providing a distinctive binding surface for the physiological partners PAI-1 and uPAR. The hydrophobic surface consists mainly of side chains from the loop formed by the Cys(25)-Cys(31) disulfide bond, and is surrounded by conserved acidic and basic side chains, which are likely to contribute to the specificity of the intermolecular interactions of this domain. Interestingly, the overall fold of the molecule is compatible with several arrangements of the disulfide bonds. A number of different disulfide bond arrangements were able to satisfy the NMR restraints, and an extensive series of conformational energy calculations performed in explicit solvent confirmed that several disulfide bond arrangements have comparable stabilization energies. An experimental demonstration of the presence of alternative disulfide conformations in active rSMB is provided by the behavior of a mutant in which Asn(14) is replaced by Met. This mutant has the same PAI-1 binding activity as rVN1-51, but its fragmentation pattern following cyanogen bromide treatment is incompatible with the linear uncrossed disulfide arrangement. These results suggest that active forms of the SMB domain may have a number of allowed disulfide bond arrangements as long as the Cys(25)-Cys(31) disulfide bond is preserved.

DNA analysis by flow cytometry is considered to be of prognostic value in epidermoid carcinoma of the head and neck. However, few and contradictory studies have been made on laryngeal carcinomas. We studied 48 epidermoid carcinomas in patients subjected to horizontal supraglottic laryngectomy with a 5-year- followup. The technique described by Hedley for fixated and paraffin-embedded tumors was used. Thirteen tumors were excluded on the grounds of presenting variation coefficients in excess of 10. Of the 35 cases analyzed, 28 (80%) were diploid and seven (20%) aneuploid. No correlation was observed between tumor ploidy and patient survival, recurrence, or any of the histopathological variables studied.