Using Iterative Experimentation to Accelerate Program Improvement: A Case Example.

Background: This article offers a case example of how experimental evaluation methods can be coupled with principles of design-based implementation research (DBIR), improvement science (IS), and rapid-cycle evaluation (RCE) methods to provide relatively quick, low-cost, credible assessments of strategies designed to improve programs, policies, or practices.

Objectives: This article demonstrates the feasibility and benefits of blending DBIR, IS, and RCE practices with embedded randomized controlled trials (RCTs) to improve the pace and efficiency of program improvement.

Research Design: This article describes a two-cycle experimental test of staff-designed strategies for improving a workforce development program.

Subcortical volumes are reduced in short-term and long-term abstinent alcoholics but not those with a comorbid stimulant disorder.

Chronic alcohol abuse affects brain structure and function. We examined subcortical structure volumes in 77 short (6-15 week) and 90 long (multi-year) term abstinent alcoholics, along with 74 controls. We used a 3T Siemens MPRAGE sequence for image acquisition and FSL FIRST software for measuring subcortical volumes.

Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections.

Objectives: We aim to develop antibacterial peptide mimics resistant to protease degradation, with broad-spectrum activity at sites of infection.

Methods: The bactericidal activities of LL-37, ceragenins CSA-13, CSA-90 and CSA-92 and the spermine-conjugated dexamethasone derivative D2S were evaluated using MIC and MBC measurements. Gingival fibroblast counting, interleukin-8 (IL-8) and lactate dehydrogenase (LDH) release from keratinocytes (HaCat) were used to determine effects on cell growth, pro-inflammatory response and toxicity.

Antisocial symptoms decrease to normal levels in long-term abstinence.

Background: We have previously shown highly elevated antisocial symptoms and measures of social deviance proneness and antisocial disposition in long-term abstinent alcohol dependence versus non-substance-abusing controls (NSAC). Current antisocial symptoms were reduced to subdiagnostic levels in long-term abstinence; however, the number of current symptoms was not measured beyond its being subdiagnostic.

Methods: Here we measured social deviance proneness, antisocial disposition, and both lifetime and current antisocial symptoms in short-term and long-term abstinent substance-dependent and NSAC samples.

Enhancers of adeno-associated virus AAV2 transduction via high throughput siRNA screening.

Intracellular barriers to adeno-associated virus (AAV) transduction may limit gene delivery. We screened a short interfering RNA (siRNA) library targeting 5,520 genes to help identify pathways that modulate AAV transduction of human endothelium. In replicate screening, 50 pools (three siRNAs per gene) resulted in greater than eightfold reporter gene expression enhancement.

Novel cationic lipids with enhanced gene delivery and antimicrobial activity.

Cationic lipids facilitate plasmid delivery, and some cationic sterol-based compounds have antimicrobial activity because of their amphiphilic character. These dual functions are relevant in the context of local ongoing infection during intrapulmonary gene transfer for cystic fibrosis. The transfection activities of two cationic lipids, dexamethasone spermine (DS) and disubstituted spermine (D(2)S), were tested as individual components and mixtures in bovine aortic endothelial cells and A549 cells.

Combined antibacterial and anti-inflammatory activity of a cationic disubstituted dexamethasone-spermine conjugate.

The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule.

Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice.

Background: The worldwide appearance of drug-resistant strains of H. pylori motivates a search for new agents with therapeutic potential against this family of bacteria that colonizes the stomach, and is associated with adenocarcinoma development. This study was designed to assess in vitro the anti-H.

Cationic lipid formulations alter the in vivo tropism of AAV2/9 vector in lung.

Physicochemical properties of gene transfer vectors play an important role in both transduction efficiency and biodistribution following airway delivery. Adeno-associated virus (AAV) vectors are currently used in many gene transfer applications; however, the respiratory epithelium remains a challenging target. We synthesized two cationic sterol-based lipids, dexamethasone-spermine (DS) and disubstituted spermine (D(2)S) for pulmonary gene targeting.