Modeling and reinforcement to combat HIV: the MARCH approach to behavior change.

Theory and research suggest that behavioral interventions to prevent HIV/AIDS may be most effective when they are personalized and affectively compelling, when they provide models of desired behaviors, and when they are linked to social and cultural narratives. Effective strategies must also take into account the opportunities and obstacles present in the local environment. The Modeling and Reinforcement to Combat HIV (MARCH) projects combine key aspects of individual behavior change with efforts to change social norms. There are 2 main components to the program: entertainment as a vehicle for education (longrunning serialized dramas on radio or television portray role models evolving toward the adoption of positive behaviors) and interpersonal reinforcement at the community level (support from friends, family members, and others can help people initiate behavior changes; support through changes in social norms is necessary for behavioral effects to be sustained over time). Both media and interpersonal intervention activities should be linked to existing resources in the community and, wherever possible, provide increased access to preventive services, supplies, and other supporting elements.

Antiproliferative mechanism of action of cryptophycin-52: kinetic stabilization of microtubule dynamics by high-affinity binding to microtubule ends.

Cryptophycin-52 (LY355703) is a new synthetic member of the cryptophycin family of antimitotic antitumor agents that is currently undergoing clinical evaluation. At high concentrations (>/=10 times the IC50), cryptophycin-52 blocked HeLa cell proliferation at mitosis by depolymerizing spindle microtubules and disrupting chromosome organization. However, low concentrations of cryptophycin-52 inhibited cell proliferation at mitosis (IC50 = 11 pM) without significantly altering spindle microtubule mass or organization. Cryptophycin-52 appears to be the most potent suppressor of microtubule dynamics found thus far. It suppressed the dynamic instability behavior of individual microtubules in vitro (IC50 = 20 nM), reducing the rate and extent of shortening and growing without significantly reducing polymer mass or mean microtubule length. Using [3H]cryptophycin-52, we found that the compound bound to microtubule ends in vitro with high affinity (Kd, 47 nM, maximum of approximately 19.5 cryptophycin-52 molecules per microtubule). By analyzing the effects of cryptophycin-52 on dynamics in relation to its binding to microtubules, we determined that approximately 5-6 molecules of cryptophycin-52 bound to a microtubule were sufficient to decrease dynamicity by 50%. Cryptophycin-52 became concentrated in cells 730-fold, and the resulting intracellular cryptophycin-52 concentration was similar to that required to stabilize microtubule dynamics in vitro. The data suggest that cryptophycin-52 potently perturbs kinetic events at microtubule ends that are required for microtubule function during mitosis and that it acts by forming a reversible cryptophycin-52-tubulin stabilizing cap at microtubule ends.

Untied: a safe alternative to restraints.

Designing safe, appropriate, and nonmanpower-dependent alternatives to the physical restraint of confused and agitated patients is a significant nursing problem. An environmental intervention is proposed to reduce restraint use, improve patient outcomes, and use nursing resources more effectively.

Familial hyperproinsulinemia. An autosomal dominant defect.

We describe a genetic defect in a kindred in whom proinsulin or a proinsulin-like material constitutes the major fraction of circulating insulin immunoreactivity in both the fasting and stimulated states. The defect, familial hyperproinsulinemia, affects eight males and 10 females in four generations of the kindred, with an autosomal dominant mode of transmission. Familial hyperproinsulinemia is asymptomatic in the affected progeny, with no apparent relation to hypoglycemia or to the development of diabetes mellitus. This genetic defect may represent either a deficiency in the proinsulin cleaving enzyme (or enzymes) within the beta cell, or more probably, an abnormal species of proinsulin.