Characterization of the spectrum of insecticidal activity of a double-stranded RNA with targeted activity against Western Corn Rootworm (Diabrotica virgifera virgifera LeConte).

The sequence specificity of the endogenous RNA interference pathway allows targeted suppression of genes essential for insect survival and enables the development of durable and efficacious insecticidal products having a low likelihood to adversely impact non-target organisms. The spectrum of insecticidal activity of a 240 nucleotide (nt) dsRNA targeting the Snf7 ortholog in Western Corn Rootworm (WCR; Diabrotica virgifera virgifera) was characterized by selecting and testing insects based upon their phylogenetic relatedness to WCR. Insect species, representing 10 families and 4 Orders, were evaluated in subchronic or chronic diet bioassays that measured potential lethal and sublethal effects. When a specific species could not be tested in diet bioassays, the ortholog to the WCR Snf7 gene (DvSnf7) was cloned and corresponding dsRNAs were tested against WCR and Colorado potato beetle (Leptinotarsa decemlineata); model systems known to be sensitive to ingested dsRNA. Bioassay results demonstrate that the spectrum of activity for DvSnf7 is narrow and activity is only evident in a subset of beetles within the Galerucinae subfamily of Chrysomelidae (>90% identity with WCR Snf7 240 nt). This approach allowed for evaluating the relationship between minimum shared nt sequence length and activity. A shared sequence length of ≥ 21 nt was required for efficacy against WCR (containing 221 potential 21-nt matches) and all active orthologs contained at least three 21 nt matches. These results also suggest that WCR resistance to DvSnf7 dsRNA due to single nucleotide polymorphisms in the target sequence of 240 nt is highly unlikely.

The effect of two different domperidone doses on maternal milk production.

BACKGROUND: The benefits of breast milk to the newborn infant are well established. The Canadian Paediatric Society recommends exclusive breastfeeding for the first 6 months of life for healthy, term infants. Mothers of premature newborns, however, may have difficulty providing an adequate supply of breast milk. Domperidone is officially used as a prokinetic agent. However, it is used widely around the world as a galactogogue. Despite its widespread use as a galactogogue, only a small number of investigators have studied domperidone for this indication. AIMS: The purpose of this study was to determine an optimal dosage of domperidone as a galactogogue. METHODS: Eligible subjects were randomized to receive domperidone 10 mg 3 times daily or domperidone 20 mg 3 times daily for 4 weeks. At week 5, the frequency was decreased to twice daily in both groups, and finally once daily for week 6. RESULTS: Over the entire first 4-week period, there was a significant increase in daily milk volumes within each group (P < .01). The between-group difference over this period, although not statistically significant, was clinically significant. Additionally, there was no significant within- or between-group difference during weeks 5 and 6. CONCLUSION: A dose of domperidone of 20 mg, 3 times daily instead of 10 mg, 3 times daily was associated with a clinical, but not statistically significant, increase in milk production.

Effects of a contemporary, exercise-based rehabilitation and cardiovascular risk-reduction program on coronary patients with abnormal baseline risk factors.

Phase II cardiac rehabilitation programs are associated with improvements in exercise tolerance, coronary risk factors, and psychosocial well-being. Nevertheless, previous reports have generally evaluated the global effectiveness of these programs (ie, on all subjects, collectively), which may serve to camouflage or attenuate the impact of these interventions on specific patient subsets. In this study, we investigated the effectiveness of a contemporary, exercise-based cardiac rehabilitation program that included a cardiovascular risk-reduction intervention, using a computerized database on 117 patients (average age, 66.5 years; 68% men; 96% white) who completed pre-phase II and post-phase II evaluations. Exercise training involved three 45- to 60-min sessions per week at minimum of 40 to 50% to a maximum of 75% oxygen uptake for 6 to 8 weeks. The effectiveness of the exercise training program was substantiated by significant (p