Structure-Guided Design of C2-Symmetric HIV-1 Protease Inhibitors Based on a Pyrrolidine Scaffold.

J Med Chem. 2008 Mar 19;
Blum A, Böttcher J, Heine A, Klebe G, Diederich WE

Infections with the human immunodeficiency virus, which inevitably lead to the development of AIDS, are still among the most serious global health problems causing more than 2.5 million deaths per year. In the pathophysiological processes of this pandemic, HIV protease has proven to be an invaluable drug target because of its essential role in the virus' replication process. By use of pyrrolidine as core structure, symmetric 3,4-bis- N-alkylsulfonamides were designed and synthesized enantioselectively from d-(-)-tartaric acid as a new class of HIV protease inhibitors. Structure-guided design using the cocrystal structure of an initial lead as starting point resulted in a second series of inhibitors with improved affinity. The binding modes of four representatives were determined by X-ray crystallography to elucidate the underlying factors accounting for the SAR. With this information for further rational design, the combination of suitable side chains resulted in a final inhibitor showing a significantly improved affinity of K i = 74 nM.

Addressing poverty as risk for disease: recommendations from CDC's consultation on microenterprise as HIV prevention.

Public Health Rep. 2008 Jan-Feb; 123(1): 9-20
Stratford D, Mizuno Y, Williams K, Courtenay-Quirk C, O'leary A

In March 2006, the Centers for Disease Control and Prevention (CDC) convened a consultation meeting to explore microenterprise as a potential human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) prevention intervention. The impulse to link microenterprise with HIV/AIDS prevention was driven by the fact that poverty is a significant factor contributing to the risk for infection. Because increasingly high rates of HIV infection are occurring among women, particularly among poor African American women in the southern United States, we focused the consultation on microenterprise as an intervention among that population. In the international arena, income generated by microenterprise has contributed to improving family and community health outcomes. This article summarizes the contributions made to the consultation by participants from the diverse fields of microenterprise, microfinance, women's studies, and public health. The article ends with recommendations for HIV/AIDS prevention and, by implication, addressing other public health challenges, through the development of multifaceted intervention approaches.

The Influence of a Physician""s Use of a Diagnostic Decision Aid on the Malpractice Verdicts of Mock Jurors.

Med Decis Making. 2008 Mar 18;
Arkes HR, Shaffer VA, Medow MA

BACKGROUND: One reason why physicians may be reluctant to use diagnostic decision aids is that such usage might increase the likelihood of an unfavorable malpractice verdict. The authors tested this hypothesis by sending a DVD of a malpractice trial to a national sample of jury-eligible adults. METHODS: There were 3 independent variables: 1) the physician did or did not use a diagnostic aid, 2) the patient's symptoms either were or were not consistent with a diagnosis of probable appendicitis, and 3) the physician's decision to operate or not operate was either concordant or discordant with the severity of the patient's symptoms. Jurors rendered a verdict, and if they deemed the physician not to have met the standard of care, they indicated how punitive they felt toward the physician. RESULTS: . Mock jurors were more likely to side with the physician-defendant if he recommended an operation when there were many symptoms and refrained when there were few symptoms compared with a physician who did the converse. The use of a decision aid had no influence on this binary standard-of-care decision. Among those physicians deemed liable by the jurors, defying the aid resulted in heightened punishment compared with heeding it. CONCLUSION: . Contrary to many physicians' fears, use of a diagnostic decision aid did not influence the likelihood of an adverse malpractice verdict. Complying with the aid's recommendation provided a measure of protection against jurors' punitiveness for those physicians deemed liable for malpractice. Key words: malpractice; decision aids; jury decision making. (Med Decis Making XXXX;XX:xx-xx).