Genetic changes that correlate with the pine-oil disinfectant-reduced susceptibility mechanism of Staphylococcus aureus.

AIMS: To identify factors associated with the Staphylococcus aureus pine-oil disinfectant-reduced-susceptibility (PD(RS)) mechanism and to describe one possible PD(RS) model. METHODS AND RESULTS: Comparative genomic sequencing (CGS) and microarray analysis were utilized to detect mutations and transcriptome alterations that occur in a S. aureus PD(RS) mutant. Mutant analysis, antimicrobial gradient plates, growth studies and 3-hydroxy-3-methylglutaryl coenzyme A synthase assays were then performed to confirm the biological consequences of the 'omics' alterations detected in a PD(RS) mutant. CGS uncovered three mutations in a PD(RS) mutant in a(n): alcohol dehydrogenase (adh), catabolite control protein A (ccpA) and an NADPH-flavin oxidoreductase (frp). These mutations lead to increased growth rates; increased transcription of an NAD-dependent D-lactate dehydrogenase gene (ddh); and increased flux through the mevalonate pathway. PD(RS) mutants demonstrated reduced susceptibility to bacitracin and farnesol, and one PD(RS) mutant displayed upregulation of bacA, a bacitracin-resistance gene. Collectively, this evidence demonstrates altered undecaprenol metabolism in PD(RS) mutants. CONCLUSIONS: The PD(RS) mechanism proposed results from increased catabolic capabilities and increased flux through the mevalonate pathway as well as altered bactoprenol physiology. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel mechanism that bacteria utilize to overcome the killing effects of PD formulations is proposed that is unique from the PD(RS) mechanism of the enterobacteraciae.

Intravenous diazepam narcosis in the treatment of injuries, with doxapram for recovery.

The effective use of diazepam for narcosis in cases of injury requiring painful manipulations is dependent on adequate dosage, titrated for each patient. Protection against the risk of occasional respiratory depression from this regime is consistently given by the use of intravenous doxapram, which also gives varying degrees of arousal.

Polymer erosion and drug release characterization of hydroxypropyl methylcellulose matrices.

Polymer erosion of matrices of similarly substituted hydroxypropyl methylcellulose (HPMC) polymers was examined, and drug release in terms of diffusion and erosion contributions was characterized, focusing on matrices containing either polymer alone or a drug content of 25% level with no added excipients. A novel approach was utilized to separate diffusional and erosional contributions to drug release. Diffusional drug release was determined by fitting release data versus (time)0.45, and the drug release due to erosion was quantified by subtracting the percent predicted for diffusional drug release from the total drug release at each specific time point. Drug release resulting from polymer erosion was linear versus time and was found to be a function of the number average molecular weight of the polymer. In contrast, diffusional release rates were comparable for all HPMC grades studied and, thus, were independent of number average molecular weight of the polymers studied. Under stirring conditions of 10-100 rpm as well as static condition, the detachment of individual polymer chains at the matrix surface occurred at a faster rate relative to diffusion away from the matrix surface. The erosion study indicated that polymer diffusion of the HPMC polymer chains through the aqueous diffusion layer was the rate-limiting step for polymer erosion. In general, polymer erosion was found to be inversely related to the polymer number average molecular weight. A scaling law was used to relate polymer erosion rate with the respective polymer number average molecular weight. Similar relationships were obtained for matrices with and without drug at a stirring rate of 100 rpm.

Quantitative studies of schizophrenic behavior.

Behavioral data from eight psychiatric patients were collected and formed into 14 time series of 100 weekly rates (percentages of positive entries for frequent behaviors such as pacing, talking, hand-movement, etc.). A variety of methods of time-series analysis were applied to determine optimal predictive schemes in an effort to develop an inductive approach to input-output behavioral modelling. Some attempts at numerical prediction into new data were successful, and the results suggested that the best overall approach is likely to be nonlinear modification of auto-regressive schemes. Nonlinearity and nonstationarity of such time series are prominent features, but deterministic trends appear strong enough to justify extensive work. Application of artificial inputs to some of the models suggests that protracted oscillatory responses to stimulation may be characteristic for some schizophrenic patients.

Effectiveness of three natural biobarriers in reducing root intrusion by four semi-arid plant species.

Plant root depth, relative density, and an Intrusion Index were determined for three grass and one shrub species growing above three different natural biobarriers. High-clay content soil was the least effective barrier. Scoria (volcanic cinder) was most effective in excluding roots of crested wheatgrass and streambank wheatgrass. Root parameters for sagebrush and Great Basin wildrye were least growing over a biobarrier mixture of gravel and cobble.

Root mass and vertical root distribution of five semi-arid plant species.

The root masses of big sagebrush, Great Basin wild rye, Russian thistle, streambank wheatgrass, and crested wheatgrass were determined at 20 cm depth increments from plants grown in high clay content soils in cylindrical containers. All species had roots in the deepest (100-120 cm) depth increment. Crested wheatgrass had the greatest average (+/- SD) total root mass (775 +/- 211 g). Results provide data for some scenarios for fate and effect models for shallow-land burial of low-level radioactive wastes in semi-arid environments.

Vertical distribution of soil removed by four species of burrowing rodents in disturbed and undisturbed soils.

Burrow volumes were determined in disturbed and undisturbed soils for four species of rodents in southeastern Idaho. Comparisons were made between soil types for the average volume and the proportion of the total volume of soil excavated from 10-cm increments for each species, and the relative number of burrows and proportion of total soil removed from beneath the minimum thickness of soil covers over buried low-level radioactive wastes. Burrows of montane voles (Microtus montanus) and deer mice (Peromyscus maniculatus) rarely extended below 50 cm and neither volumes nor depths were influenced by soil disturbance. Townsend's ground squirrels (Spermophilus townsendii) had the deepest and most voluminous burrows that, along with Ord's kangaroo rat (Dipodomys ordii) burrows, were more prevalent beneath 50 cm in disturbed soils.

Behavioral rhythms in schizophrenia.

Daily behavioral observations were made for several years on 10 male schizophrenic patients and on three male patients with organic brain disorders. Analysis of these data showed strong cyclic components in the five schizophrenic patients with predominantly hebephrenic symptomatology. Period lengths noted were about 2 days, 5 to 6 days, 30 days, and a longer cycle of 40 to 100 days duration. Antipsychotic medications appear to have a suppressant effect, but tricyclic antidepressants may enhance pre-existing rhythms.