This study explored the therapeutic alliance and satisfaction between transgender clients and their therapists. The design was qualitative and heuristically based. Seven transgendered participants who had lived full-time as their non-natal gender for at least three months and who had spent at least the majority of a course of therapy discussing their current gender identity were recruited. Interviews were semistructured, and each was transcribed verbatim. Three levels of coding were used for analysis: seven individual depictions in narrative form, a single composite depiction bringing together similarities between the experiences of the participants, and a single exemplary depiction of critical themes. Results suggest that the participants did not experience many of the heterosexist, sexist, and pathologizing biases described in previous studies. Rather, they described supportive and affirming relationships with their therapists. Some participants had had negative experiences with previous therapists. Participants called for further training and education for therapists and other helping professionals. Implications for theory, research, practice, and policy are explored.
Implementation and use of an electronic pop-up alert in an inpatient psychiatric unit significantly improved rates of ordering fasting blood glucose and lipid levels for inpatients treated with SGAs. Overall rates remain suboptimal, suggesting a need for additional strategies to further improve metabolic monitoring.
Indandiones were identified as a novel class of small molecule inhibitors of hepatitis C virus NS3 serine protease from high throughput screening. We further studied the structure activity relationships and the mechanisms of inhibition for this class of compounds. Our studies revealed two similar, yet different, mechanisms accounting for the apparent indandione inhibition of HCV NS3 protease. In one case, the apparent inhibition results from the chemical breakdown of the parent compound and the subsequent redox chemistry of the compound. Oxidation of the cysteine containing substrate A to a disulfide-linked dimer converts this substrate to a potent, slow-binding inhibitor with a K(i) value of 170 nM. The second class of indandiones appears to react directly with the substrate to form an S-phenyl disulfide adduct with the P1 cysteine. This modification converts the substrate to a slow-binding inhibitor with a K(i) value of 110 nM, a k(on) = 2370 M(-1) s(-1), and k(off) = 2.5 x 10(-4) s(-1). A stable analogue of this latter compound was synthesized that contained a CH(2)-S linkage instead of the S-S linkage. The CH(2)-S compound showed no inhibition at concentrations as high as 40 microM, which suggests an important role for the S-S linkage in the inhibitory mechanism. Cysteine 159, which lies near the active site of the HCV protease, was mutated to serine. The C159S mutant displayed wild-type catalytic activity and susceptibility to inhibition by the S-S linked inhibitor. This result argues against a mechanism involving disulfide exchange between the inhibitor and the sulfhydryl group of C159. The mechanism of inhibition for this S-S linked substrate based inhibitor is likely due to oxidation of cysteines involved in chelation of the structural zinc atom.
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