Role of Mediators in Reducing Antepartum Depressive Symptoms in Rural Low-Income Women Receiving a Culturally Tailored Cognitive Behavioral Intervention.

Although cognitive behavioral interventions (CBIs) have demonstrated effectiveness for reducing depressive symptoms in the general population, the mechanism for reducing antepartum depressive symptoms (APDS) in rural low-income and minority women is unknown. This study tested the hypothesis that reducing stress and negative thinking, enhancing self-esteem, and increasing social-support will mediate the effect of a CBI on reducing APDS in rural low-income and minority women. Our findings show that CBI may work through reducing stress and negative thinking and enhancing self-esteem, but not social support. The findings also suggest that mental health care providers should emphasize these activities to reduce antepartum depressive symptoms.

Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach.

PURPOSE: To develop a strategy to control benzene, an ICH Q3C Class 1 impurity that may be present in spray solvents at ppm concentration, in amorphous polymer-stabilized spray-dried dispersion (SDD) products. METHODS: Risk assessments included determining the probability for benzene concentration in primary spray solvents, the physical properties of volatiles, and the potential enrichment of benzene from solution to solid. Mechanistic understanding of benzene removal was gained through a benzene-spiked fate and tolerance (F&T) study simulating worst-case spray-drying conditions and application of diffusion models for secondary drying. RESULTS: The mass ratio of spray solution to solid presented the highest risk of benzene enrichment. With slow spray-drying kinetics, benzene was reduced about 700-fold. Under standard secondary-drying conditions to remove residual solvents, residual benzene was further removed. Using diffusion models, the maximum benzene concentration was approximated for SDDs dried to the in-process control (IPC) limit of primary solvents. CONCLUSIONS: Two critical control points were established to eliminate any risk of residual benzene reaching patients: (1) upstream control of benzene in solvents (≤10 ppm) and (2) IPC of residual solvents in polymer-stabilized SDDs.

Breastfeeding among high-risk inner-city African-American mothers: a risky choice?

OBJECTIVE: This study identified barriers to breastfeeding among high-risk inner-city African-American mothers. SUBJECTS AND METHODS: We used audiotaped focus groups moderated by an experienced International Board Certified Lactation Consultant, with recruitment supported by the community partner MomsFirst™ (Cleveland Department of Public Health, Cleveland, OH). Institutional Review Board approval and written informed consent were obtained. Notes-based analysis was conducted with use of a prior analytic structure called Factors Influencing Beliefs (FIBs), redefined with inclusion/exclusion criteria to address breastfeeding issues. RESULTS: Three focus groups included 20 high-risk inner-city expectant and delivered mothers. Relevant FIBs domains were as follows: Risk Appraisal, Self Perception, Relationship Issues/Social Support, and Structural/Environmental Factors. Risk Appraisal themes included awareness of benefits, fear of pain, misconceptions, and lack of information. Self Perception themes included low self-efficacy with fear of social isolation and limited expression of positive self-esteem. Relationship Issues/Social Support themes included formula as a cultural norm, worries about breastfeeding in public, and challenging family relationships. Structural/Environmental Factors themes included negative postpartum hospital experiences and lack of support after going home. CONCLUSIONS: Several findings have been previously reported, such as fear of pain with breastfeeding, but we identified new themes, including self-esteem and self-efficacy, and new concerns, for example, that large breasts would suffocate a breastfeeding infant. The FIBs analytic framework, as modified for breastfeeding issues, creates a context for future analysis and comparison of related studies and may be a useful tool to improve understanding of barriers to breastfeeding among high-risk inner-city women.

Inhibition of cobalamin-dependent methionine synthase by substituted benzo-fused heterocycles.

The cobalamin-dependent cytosolic enzyme, methionine synthase (EC.2.1.1.13), catalyzes the remethylation of homocysteine to methionine using 5-methyltetrahydrofolate as the methyl donor. The products of this remethylation--methionine and tetrahydrofolate--participate in the active methionine and folate pathways. Impaired methionine synthase activity has been implicated in the pathogenesis of anaemias, cancer and neurological disorders. Although the need for potent and specific inhibitors of methionine synthase has been recognized, there is a lack of such agents. In this study, we designed, synthesized and evaluated the inhibitory activity of a series of substituted benzimidazoles and small benzothiadiazoles. Kinetic analysis revealed that the benzimidazoles act as competitive inhibitors of the rat liver methionine synthase, whilst the most active benzothiadiazole (IC(50) = 80 microm) exhibited characteristics of uncompetitive inhibition. A model of the methyltetrahydrofolate-binding site of the rat liver methionine synthase was constructed; docking experiments were designed to elucidate, in greater detail, the binding mode and reveal structural requirements for the design of inhibitors of methionine synthase. Our results indicate that the potency of the tested compounds is related to a planar region of the inhibitor that can be positioned in the centre of the active site, the presence of a nitro functional group and two or three probable hydrogen-bonding interactions.