Functional advantages of building nanosystems using multiple molecular components.

Over half of all the natural nanomachines in living organisms are multimeric and likely exploit the self-assembly of their components to provide functional benefits. However, the advantages and disadvantages of building nanosystems using multiple molecular components remain relatively unexplored at the thermodynamic, kinetic and functional levels. In this study we used theory and a simple DNA-based model that forms the same nanostructures with different numbers of components to advance our knowledge in this area. Despite its lower assembly rate, we found that a system built with three components may undergo a more cooperative assembly transition from less preorganized components, which facilitates the emergence of functionalities. Using simple variations of its components, we also found that trimeric nanosystems display a much higher level of programmability than their dimeric counterparts because they can assemble with various levels of cooperativity, self-inhibition and time-dependent properties. We show here how two simple strategies (for example, cutting and adding components) can be employed to efficiently programme the regulatory function of a more complex, artificially selected, RNA-cleaving catalytic nanosystem.

Building better hospital transfusion committees for Ontario.

Hospital transfusion committees can be instrumental in ensuring appropriate blood utilization and that best practice standards are followed. In Ontario, Canada, the provincial Ministry of Health and Long-Term Care Blood Programs Coordinating Office has implemented several initiatives to support these multi-disciplinary hospital committees to fulfill their mandate. The primary goal is to improve patient safety and the secondary goal is to reinforce the importance of appropriate use of blood components and blood products. Recognizing the challenges in developing a fully functional hospital transfusion committee, several initiatives have been launched to provide educational resources and tools to achieve a successful outcome. The number of hospital transfusion committees in Ontario has increased over the past 5 years. Attendance at the annual educational forum for transfusion committees continues to be high. The majority of hospitals are using the resources and tools being provided. More work is needed to achieve the success of this strategy.

The effect of carrier for vitamin E on liver concentrations of vitamin E and vitamin E excretion in broilers.

Two experiments were conducted to determine the effect of 2 carrier sources of vitamin E on growth performance and excreta and liver vitamin E concentrations of broilers. Chicks were pretested from d 0 to 7 posthatching on a corn-soybean meal diet without vitamin E supplementation, and the experiments lasted from d 7 to 19 posthatching. Each treatment in both experiments was replicated with 6 pens with 5 chicks each. Initial and final BW were 155 and 684 g in experiment 1 and 155 and 691 g in experiment 2. In experiment 1, the dietary treatments were the corn-soybean meal diet with varying concentrations (0, 30, 100, or 300 IU/kg) of supplemental vitamin E either absorbed to verxite (VE) or adsorbed to silica (SE). In experiment 2, the dietary treatments were the 0 and 30 IU/kg of vitamin E as VE or SE. In experiment 1, feed intake decreased and gain:feed increased as concentration of VE increased, but feed intake increased and gain:feed decreased as concentration of SE increased (source x concentration, P < 0.03). Gain, feed intake, and gain:feed were not affected (P > 0.10) by the vitamin E carrier source in experiment 2. The mean excreta vitamin E concentration at d 7 posthatching was 17.2 IU/kg (DM basis). The percentages of vitamin E excreted were based on analyzed vitamin E concentrations in the diet. At 100 and 300 IU/kg of supplemental vitamin E, an average of 94 and 44% of vitamin E intake from broilers fed vitamin E from VE and SE, respectively, was excreted (vitamin E source, P < 0.01; source x concentration, P < 0.08), but at 30 IU/kg of vitamin E, 49 and 45% of vitamin E intake from broilers fed vitamin E from VE and SE was excreted. In experiment 2, 52 and 43% of vitamin E intake from VE and SE was excreted (source, P < 0.02). Liver alpha-tocopherol concentration was not different (P > 0.10) between the sources of vitamin E in either experiment. Increased concentrations of vitamin E increased liver alpha-tocopherol concentrations (P < 0.01). On the basis of the results of excreted vitamin E, vitamin E adsorbed to SE was more available than vitamin E absorbed to VE, but on the basis of liver vitamin E concentration, their availabilities were similar.

Pathogens in children with severe combined immune deficiency disease or AIDS.

We evaluated the frequency and severity of illnesses caused by various microbial pathogens in 15 children with severe combined immune deficiency disease (SCID) and 8 with acquired immune deficiency syndrome (AIDS). There were 35 viral, 23 bacterial, 19 mycotic and 13 parasitic infections. Nineteen of the 23 patients died of infection; Pneumocystis carinii pneumonia, giant-cell pneumonia due to paramyxoviruses and various disseminated viral infections were responsible for most deaths in both groups. The emerging role of paramyxoviruses was illustrated by the fact that they were responsible for giant-cell pneumonia in seven patients. Viral enteric infections were frequent in both groups. The variety of infectious microorganisms and the severity of resulting illnesses in the patients with AIDS were similar to those in the patients with SCID.

Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin.

Serum bactericidal activities (SBAs) were studied after intravenous administration of pefloxacin (8 mg/kg) and amikacin (7.5 mg/kg) alone or in combination to 15 human volunteers. About 10 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested. The serum levels of pefloxacin were measured microbiologically by using E. coli KP 1976-712 as the test organism at 0, 30, 60, 120, and 720 min after infusion; at 0, 30, 60, and 720 min these levels were 7 +/- 1.4, 5 +/- 0.8, 4.5 +/- 0.7, and 2.1 +/- 0.6 mg/liter (mean +/- standard deviation), respectively, with a terminal half-life of 10 h. The serum levels of pefloxacin in the presence of amikacin were measured similarly; 1% sodium polyanethol sulfonate was added to the agar to inactivate amikacin. Treatment with pefloxacin alone resulted in high SBAs against E. coli, K. pneumoniae strains susceptible to cephalothin, and Staphylococcus aureus at the peak concentration; 81 to 100% of the sera had SBAs of greater than or equal to 1:8. However, treatment with pefloxacin alone resulted in low SBAs against K. pneumoniae strains resistant to cephalothin and P. aeruginosa; only 34% of the sera had SBAs of greater than or equal to 1:8. At trough concentrations the percentages of sera with SBAs greater than or equal to 1:8 were 75 to 83% (E. coli), 9 to 27% (K. pneumoniae), 0% (P. aeruginosa), and 10% (S. aureus). The combination of pefloxacin plus amikacin was most often additive; the peak activity was due to amikacin, and the trough activity was due to pefloxacin. Occasionally antagonism occurred with P. aeruginosa, K. pneumoniae, and S. aureus strains. These observations were confirmed by the killing curves in pooled serum obtained at peak and trough levels. Regrowth was observed for seven strains of P. aeruginosa treated with pefloxacin alone; amikacin seemed to prevent this phenomenon.