Simvastatin attenuates the activity of matrix metalloprotease-9 in aneurysmal aortic tissue.

To investigate whether statins reduce the concentration of MMP-9 in the aortic wall, we randomised patients undergoing elective open repair of an abdominal aortic aneurysm (AAA) to a pre-operative course of either simvastatin or placebo. MMPs in aortic biopsies were measured using gelatin zymography. Although recruitment closed early because of increasing statin use among eligible patients, with only 21 patients we demonstrated a 40% reduction in MMP-9 levels in the AAA wall in patients randomised to simvastatin. This provides a possible molecular mechanism to explain the reportedly beneficial effects of statins to slow AAA growth.     

The moderating effect of adherence-promoting interventions with clients on evidence-based practices for children and adolescents with mental health problems

Poor adherence of children and adolescents to evidence-based psychosocial interventions remains a fundamental impediment to treatment effectiveness. To maintain client adherence, researchers and clinicians have employed a number of adherence-promoting strategies, from telephone calls and letters to providing transportation costs and child care to motivational enhancement therapies. However, the influence of adherence promoters on intervention outcomes has not been reported. This study examined the moderating effect of adherence-promoting strategies in a survey and meta-analysis of randomized clinical trials of cognitive behavioral treatments, interpersonal therapy, and psycho-education for children and adolescents with mental health problems (k?=?33). Results indicated the type and intensity of adherence promoters' moderated study effect sizes according to client characteristics (age, gender, diagnosis). Preliminary findings suggest that males had higher effect sizes when more intensive adherence-promoting efforts were employed. Adherence-promoting efforts were associated with lower effect sizes for youths who were diagnosed with externalizing disorders. Results of this study suggest directions for future research to clarify clinical guidelines to maximize retention in evidence-based psychotherapy.     

An analysis of how the GAVI alliance and low- and middle-income countries can share costs of new vaccines

Immunization is one of the "best buys" in global health. However, for the poorest countries, even modest expenditures may be out of reach. The GAVI Alliance is a public-private partnership created to help the poorest countries introduce new vaccines. Since 2008 GAVI has required that countries cover a share of the cost of vaccines introduced with GAVI support. To determine how much countries can contribute to the cost of vaccines--without displacing spending on other essential programs--we analyzed their fiscal capacity to contribute to the purchase of vaccines over the coming decade. For low-income countries, external financing will be required to purchase vaccines supported by GAVI, so co-financing needs to be modest. Relatively better-off "intermediate" countries could support initially modest but gradually increasing co-financing levels. The countries soon to graduate from GAVI can generally afford to follow a rapid path to self-sufficiency. Co-financing for these countries needs to ramp up so that national budgets fully cover the costs of the new generation of vaccines once GAVI support ends.     

Ueber die parenchymatöse und subcutane Injection des Alkohols und ähnlich wirkender Stoffe

Ohne Zusammenfassung     

Solution 19F nuclear Overhauser effects in structural studies of the cytoplasmic domain of mammalian rhodopsin

19F nuclear Overhauser effects (NOEs) between fluorine labels on the cytoplasmic domain of rhodopsin solubilized in detergent micelles are reported. Previously, high-resolution solution (19)F NMR spectra of fluorine-labeled rhodopsin in detergent micelles were described, demonstrating the applicability of this technique to studies of tertiary structure in the cytoplasmic domain. To quantitate tertiary contacts we have applied a transient one-dimensional difference NOE solution (19)F NMR experiment to this system, permitting assessment of proximities between fluorine labels specifically incorporated into different regions of the cytoplasmic face. Three dicysteine substitution mutants (Cys-140-Cys-316, Cys-65-Cys-316, and Cys-139-Cys-251) were labeled by attachment of the trifluoroethylthio group through a disulfide linkage. Each mutant rhodopsin was prepared (8-10 mg) in dodecylmaltoside and analyzed at 20 degrees C by solution (19)F NMR. Distinct chemical shifts were observed for all of the rhodopsin (19)F labels in the dark. An up-field shift of the Cys-316 resonance in the Cys-65-Cys-316 mutant suggests a close proximity between the two residues. When analyzed for (19)F-(19)F NOEs, a moderate negative enhancement was observed for the Cys-65-Cys-316 pair and a strong negative enhancement was observed for the Cys-139-Cys-251 pair, indicating proximity between these sites. No NOE enhancement was observed for the Cys-140-Cys-316 pair. These NOE effects demonstrate a solution (19)F NMR method for analysis of tertiary contacts in high molecular weight proteins, including membrane proteins.