trans-Activation and repression properties of the novel nonsteroid glucocorticoid receptor ligand 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-y1)-1H-[1]benzopyrano[3,4-f]quinoline (A276575) and its four stereoisomers

Glucocorticoids are potent anti-inflammatory and immunosuppressant agents. However, they also produce serious side effects that limit their usage. It has been proposed that anti-inflammatory properties of glucocorticoids are caused mostly by repression of activator protein 1- and nuclear factor kappabeta-stimulated synthesis of inflammatory mediators, whereas most of their adverse effects are associated with trans-activation of genes involved with metabolic processes. Our laboratories have sought to discover novel glucocorticoid receptor (GR) ligands that have high repression but low trans-activation activities. We describe here cellular properties of 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-y1)-1H-[1]benzopyrano[3,4-f]quinoline (A276575) and its four enantiomers. Similar to dexamethasone, A276575 exhibited high affinity for GR and potently repressed interleukin (IL) 1beta-stimulated IL-6 production in human skin fibroblasts, prostaglandin (PG) E(2) production in A549 human lung epithelial cells, and concanavalin A-induced monocyte proliferation. In contrast to dexamethasone, A276575 caused smaller induction of aromatase activity in human skin fibroblasts and antagonized dexamethasone-induced activation of an mouse mammary tumor virus-glucocorticoid-response element (GRE) reporter gene construct. Among the four enantiomers of A276575, the two (-)-enantiomers showed 10- to 30-fold higher affinities for GR than their respective (+)-enantiomers. Both (-)-Syn and (-)-Anti enantiomers of A276575 were potent inhibitors of IL-1beta-stimulated PGE2 production in A549 lung epithelial cells; unexpectedly, however, only the (-)-Anti enantiomer inhibited regulated on T-cell activation, normal T-cell expressed and secreted (RANTES) production in A549 cells. In summary, A276575 is a novel, nonsteroidal GR ligand that possesses high repression activities against inflammatory mediator production but has lower GRE trans-activation activities than traditional steroids. Differential repression of RANTES and PGE2 production in a cell by the two (-)-enantiomers of A276575 illustrates the complexity of repression by GR.     

Credentialing the public health workforce: an idea whose time has come.

The importance of a well-prepared public health workforce is widely recognized and appreciated. Strategies for enhancing workforce capacity and competency have been discussed by agencies, associations, committees, and expert panels since the landmark 1988 Institute of Medicine report. The need to foster the development of incentives for lifelong learning and career growth is of current interest to national public health associations and federal agencies. The fact that the public health workforce is not a single profession, but rather a fabric of many professions dedicated to a common endeavor, creates challenges to any singular approach. This article explores the relationships among competency, certification, and accreditation and summarizes the expert panel dialogue on workforce development incentives, specifically regarding certification and credentialing. The authors challenge public health leaders to become actively involved in framing the issues so the best possible strategies can be developed.     

Amplifying diffusion of health information in low-literate populations through adult education health literacy classes

Over the next decade, as literacy rates are predicted to decline, the health care sector faces increasing challenges to effective communication with low-literate groups. Considering the rising costs of health care and the forthcoming changes in the American health care system, it is imperative to find nontraditional avenues through which to impart health knowledge and functional skills. This article draws on classroom observations and qualitative interviews with 21 students and 3 teachers in an adult education health literacy class to explore the efficacy of using adult education courses to teach functional health literacy skills to low-literate populations. Data were analyzed using a combination of thematic and content analyses. Results describe the motivation of students to share information within the classroom and with friends and family outside the classroom. This article also provides several recommendations to help ensure accuracy of diffused information both within and outside of the classroom. Ultimately, this study suggests that the adult education system is in a prime position to impart functional health literacy skills to low-literate populations in the classroom. Significantly, this study demonstrates that adult education students themselves may be a powerful vehicle for health communication beyond the walls of the classroom.     

Building capacity for success: the Tobacco Technical Assistance Consortium

The Master Settlement Agreement with the tobacco industry has infused resources into tobacco control and prevention, which has helped fund tobacco control programs at the national, state, and local levels. Many tobacco control programs face challenges in areas such as strategic planning, fiscal operations, advocacy, and personnel management. To provide technical assistance to these programs, the Robert Wood Johnson Foundation, the American Legacy Foundation, and the American Cancer Society combined resources to fund the Tobacco Technical Assistance Consortium (TTAC). TTAG, housed at the Rollins School of Public Health at Emory University, provides support for tobacco control programs and matches requests for technical assistance with consultants who have the appropriate expertise. TTAC is a valuable addition to tobacco control and prevention resources and is a viable component within a school of public health.     

Posthemorrhagic hemispheric cysts in neonates: treatment by cystoventriculostomy

Two premature infants developed enlarging symptomatic hemispheric cysts secondary to intraparenchymal hemorrhages. Computed tomographic scans obtained after metrizamide was injected into the cysts demonstrated that they were isolated from the ventricular system. The cysts were treated by biopsy of the common cyst-ventricular wall through a ventriculoscope. Both patients have been followed for over 1 year. Repeat scans have demonstrated resolution of the cysts, a return to midline of the ventricular system, and an increase in the volume of cerebral tissue. The original abnormal neurological signs have disappeared, and the developmental progress has been excellent.