Using Group Model Building to Describe the System Driving Unhealthy Eating and Identify Intervention Points: A Participatory, Stakeholder Engagement Approach in the Caribbean.

Many Small Island Developing States of the Caribbean experience a triple burden of malnutrition with high rates of obesity, undernutrition in children, and iron deficiency anemia in women of reproductive age, driven by an inadequate, unhealthy diet. This study aimed to map the complex dynamic systems driving unhealthy eating and to identify potential points for intervention in three dissimilar countries. Stakeholders from across the food system in Jamaica (n = 16), St. Kitts and Nevis (n = 19), and St. Vincent and the Grenadines (n = 6) engaged with researchers in two group model building (GMB) workshops in 2018. Participants described and mapped the system driving unhealthy eating, identified points of intervention, and created a prioritized list of intervention strategies. Stakeholders were also interviewed before and after the workshops to provide their perspectives on the utility of this approach. Stakeholders described similar underlying systems driving unhealthy eating across the three countries, with a series of dominant feedback loops identified at multiple levels. Participants emphasized the importance of the relative availability and price of unhealthy foods, shifting cultural norms on eating, and aggressive advertising from the food industry as dominant drivers. They saw opportunities for governments to better regulate advertising, disincentivize unhealthy food options, and bolster the local agricultural sector to promote food sovereignty. They also identified the need for better coordinated policy making across multiple sectors at national and regional levels to deliver more integrated approaches to improving nutrition. GMB proved to be an effective tool for engaging a highly diverse group of stakeholders in better collective understanding of a complex problem and potential interventions.

Different types of asynchronous music and effects on performance of basketball foul shot.

48 undergraduate women performed basketball foul shots with and without background music. Slow music, fast music, and music personally selected by subjects did not significantly affect shooting performance.

Thio- and oxoflavopiridols, cyclin-dependent kinase 1-selective inhibitors: synthesis and biological effects.

Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC(50) of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.

Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl biphenylsulfonamides as a new class of potent, highly selective ET(A) antagonists.

The synthesis and structure-activity relationship (SAR) studies of a series of 4'-oxazolyl-N-(3,4-dimethyl-5-isoxazolyl)[1, 1'-biphenyl]-2-sulfonamide derivatives as endothelin-A (ET(A)) receptor antagonists are described. The data reveal a remarkable improvement in potency and metabolic stability when the 4'-position of the biphenylsulfonamide is substituted with an oxazole ring. Additional 2'-substitution of an acylaminomethyl group further increased the binding activity and provided one of the first subnanomolar ET(A)-selective antagonists in the biphenylsulfonamide series (17, ET(A) K(i) = 0.2 nM). Among the compounds described, 3 (N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1, 1'-biphenyl]-2-sulfonamide; BMS-193884) had the optimum pharmacological profile and was therefore selected as a clinical candidate for studies in congestive heart failure.