ABSTRACT
There is significant potential for delivering speech-language pathology services using telemedicine methods. However, current telemedicine and videoconferencing equipment has limitations that constrain the speech-language therapeutic interventions that can be delivered remotely. This work aimed to develop a telemedicine system that would extend the capabilities of existing videoconferencing equipment and integrate an array of clinically relevant and validated therapeutic tools and techniques. Through a user-centered iterative design framework, an earlier prototype system was expanded and enhanced to enable greater interaction between a speech-language clinician and client during a telemedicine session. The final system utilizes H.323 Internet-based videoconferencing with integrated T.120 data sharing features and allows for a wide range of treatment material and therapeutic interventions to be delivered to a remote client. The protocol for a case-study evaluation designed to evaluate the system as a means for providing comprehensive speech-language treatment has been developed and testing is underway. Preliminary results indicate that the system is a viable alternative to face-to-face treatment for adult clients with neurological impairments.
ABSTRACT
As a strategy to increase the penetration of antibiotic drugs through the outer membrane of gram-negative pathogens, facilitated transport through siderophore receptors has been frequently exploited. Hydroxamic acids, catechols, or very close isosteres of catechols, which are mimics of naturally occurring siderophores, have been used successfully as covalently linked escorting moieties, but a much wider diversity of iron binding motifs exists. This observation, coupled to the relative lack of specificity of siderophore receptors, prompted us to initiate a program to identify novel, noncatechol siderophoric structures. We screened over 300 compounds for their ability to (1) support growth in low iron medium of a Pseudomonas aeruginosa siderophore biosynthesis deletion mutant, or (2) compete with a bactericidal siderophore-antibiotic conjugate for siderophore receptor access. From these assays we identified a set of small molecules that fulfilled one or both of these criteria. We then synthesized these compounds with functional groups suitable for attachment to both monobactam and cephalosporin core structures. Siderophore-beta-lactam conjugates then were tested against a panel of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Although several of the resultant chimeric compounds had antimicrobial activity approaching that of ceftazidime, and most compounds demonstrated very potent activity against their cellular targets, only a single compound was obtained that had enhanced, siderophore-mediated antibacterial activity. Results with tonB mutants frequently showed increased rather than decreased susceptibilities. suggesting that multiple factors influenced the intracellular concentration of the drugs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Siderophores/pharmacology , Escherichia coli/drug effects , Magnetic Resonance Spectroscopy , Mass Spectrometry , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Siderophores/chemistry , Staphylococcus aureus/drug effects , beta-LactamsABSTRACT
In a taste-aversion test pairing saccharin and ethanol, rats that had recently ingest ethanol showed attenuated aversion to saccharin.
Subject(s)
Avoidance Learning/drug effects , Conditioning, Psychological/drug effects , Ethanol/pharmacology , Taste/drug effects , Animals , Drinking/drug effects , Drug Tolerance , Male , Rats , SaccharinABSTRACT
Three groups of animals (two of rats and one of mice) were tested to determine the effects of alcohol deprivation and the addition of sweetener to an alcohol solution on the animals' intake of alcohol.
