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Objectives: An adverse event (AE) is a physical harm experienced by a patient due to health care, requiring intervention. Describing and categorizing AEs is important for quality and safety assessment and identifying areas for improvement. Safety science suggests that improvement efforts should focus on preventing and mitigating harm rather than on error, which is commonplace but infrequently leads to AEs. Most taxonomies fail to describe harm experienced by patients (e.g., hypoxia, hemorrhage, anaphylaxis), focusing instead on errors, and use categorizations that are too broad to be useful (e.g., "communication error"). We set out to create a patient-centered, emergency department (ED)-specific framework for describing AEs and near misses to advance quality and safety in the acute care setting., Methods: We performed a critical review of existing taxonomies of harm, evaluating their applicability to the ED. We identified and adopted a classification framework and developed a taxonomy using an iterative process categorizing approximately 600 previously identified AEs and near misses. We reviewed this taxonomy with collaborators at four medical centers, receiving feedback and providing clarification. We then disseminated a set of representative scenarios for these safety experts to categorize independently using the taxonomy. We calculated interrater reliability and performance compared to our criterion standard., Results: Our search identified candidate taxonomies for detailed review. We selected the Adventist Health Systems AE taxonomy and modified this for use in the ED, adopting a framework of categories, subcategories, and up to three modifiers to further describe events. On testing, overall reviewer agreement with the criterion standard was 92% at the category level and 88% at the subcategory level. Three of the four raters concurred in 55 of 59 scenarios (93%) and all four concurred in 46 of 59 scenarios (78%). At the subcategory level, there was complete agreement in 40 of 59 (68%) scenarios and majority agreement in 55 of 59 instances (93%). Performance of individual raters ranged from very good (88%, 52/59) to near perfect (98%, 58/59) at the main category level., Conclusions: We developed a taxonomy of AEs and near misses for the ED, modified from an existing framework. Testing of the tool with minimal training yielded high performance and good inter-rater reliability. This taxonomy can be adapted and modified by EDs seeking to enhance their quality and safety reviews and characterize harm occurring in their EDs for quality improvement purposes., (© 2019 by the Society for Academic Emergency Medicine.)

We here report the first comparative proteomics of purified yeast post-Golgi vesicles (PGVs). Vesicle samples isolated from PGV-accumulating sec6-4 mutants were treated with isobaric tags (iTRAQ) for subsequent quantitative tandem mass spectrometric analysis of protein content. After background subtraction, a total of 66 vesicle-associated proteins were identified, including known or assumed vesicle residents as well as a fraction not previously known to be PGV associated. Vesicles isolated from cells lacking the polarity protein Sro7p contained essentially the same catalogue of proteins but showed a reduced content of a subset of cargo proteins, in agreement with a previously shown selective role for Sro7p in cargo sorting., (© 2011 John Wiley & Sons A/S.)

Under anaerobic conditions S. cerevisiae produces glycerol to regenerate NAD(+) from the excess NADH produced in cell metabolism. We here report on the role of an uncharacterized protein, Yig1p (Ypl201cp), in anaerobic glycerol production. Yig1p was previously shown to interact in two-hybrid tests with the GPP1 and GPP2 encoded glycerol 3-phosphatase (Gpp), and we here demonstrate that strains overexpressing YIG1 show strongly decreased Gpp activity and content of the major phosphatase, Gpp1p. However, cells overexpressing YIG1 exhibited only slightly decreased GPP1 transcript levels, suggesting that Yig1p modulates expression on both transcriptional and post-transcriptional levels. In agreement with such a role, a GFP-tagged derivate of Yig1p was localized to both the cytosol and the nucleus. Deletion or overexpression of YIG1 did not, however, significantly affect growth yield or glycerol yield in anaerobic batch cultures, which is consistent with the previously proposed low flux control exerted at the Gpp level., (Copyright 2005 John Wiley & Sons, Ltd.)

Maintenance of a cytoplasmic redox balance is a necessity for sustained cellular metabolism. Glycerol formation is the only way by which Saccharomyces cerevisiae can maintain this balance under anaerobic conditions. Aerobically, on the other hand, several different redox adjustment mechanisms exist, one of these being the glycerol 3-phosphate (G3P) shuttle. We have studied the importance of this shuttle under aerobic conditions by comparing growth properties and glycerol formation of a wild-type strain with that of gut2 delta mutants, lacking the FAD-dependent glycerol 3-phosphate dehydrogenase, assuming that the consequent blocking of G3P oxidation is forcing the cells to produce glycerol from G3P. To impose different demands on the redox adjustment capability we used various carbon sources having different degrees of reduction. The results showed that the shuttle was used extensively with reduced substrate such as ethanol, whereas the more oxidized substrates lactate and pyruvate, did not provoke any activity of the shuttle. However, the absence of a functional G3P shuttle did not affect the growth rate or growth yield of the cells, not even during growth on ethanol. Presumably, there must be alternative systems for maintaining a cytoplasmic redox balance, e.g. the so-called external NADH dehydrogenase, located on the outer side of the inner mitochondrial membrane. By comparing the performance of the external NADH dehydrogenase and the G3P shuttle in isolated mitochondria, it was found that the former resulted in high respiratory rates but a comparably low P/O ratio of 1.2, whereas the shuttle gave low rates but a high P/O ratio of 1.7. Our results also demonstrated that of the two isoforms of NAD-dependent glycerol 3-phosphate dehydrogenase, only the enzyme encoded by GPD1 appeared important for the shuttle, since the enhanced glycerol production that occurs in a gut2 delta strain proved dependent on GPD1 but not on GPD2.

Background: Paclitaxel (Taxol, Bristol-Myers Squibb, Princeton, NJ) is a promising drug for the treatment of ovarian cancer. Exposure times and dose-response relationships should be explored to optimize future clinical applications of this drug., Methods: The cytotoxic effects of paclitaxel on four human ovarian cancer cell lines (Caov-3, SK-OV-3, NIH: OVCAR-3, and A2780) were analyzed using chromium-51 release assays and tetrazolium-based colorimetric assays. Cells were exposed to paclitaxel for 4 and 24 hours at concentrations ranging from 10(-10)-10(-4) M. Two paclitaxel preparations were compared: paclitaxel in DMSO and paclitaxel in cremophor EL, the carrier used in pharmacological preparations. Cell cycle analysis compared cells exposed to 10(-5) M paclitaxel in dimethyl sulfoxide for 4 hours to those exposed for 24 hours., Results: No difference in cell proliferation was demonstrated after 4 hours of treatment when compared with 24 hours of treatment with paclitaxel in dimethyl sulfoxide at 24, 48 and 72 hours after treatment in any of the cell lines tested, over all concentrations tested. When paclitaxel in cremophor was used, there was a significant decrease in cell proliferation only at 10(-4) M of paclitaxel. Similar results were seen with 10(-4) M equivalent concentration of the carrier alone. A cell cycle shift to G2/M was the same after 4 or 24 hours of exposure when assessed at 24 hours., Conclusions: A dose escalation from 10(-10) M to 10(-4) M of paclitaxel in dimethyl sulfoxide did not inhibit cell proliferation significantly in any of these cell lines. Moreover, shorter exposure times did not appear to alter the cellular response to paclitaxel. Consequently, administration of smaller dosages over shorter time periods may not compromise the cytotoxic effect of this agent. Clinical studies must be performed to validate these observations.

Study Objective: To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography., Design: This was a prospective, randomized, double-blind, placebo-controlled study., Patients: The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years., Results: We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours. Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans., Conclusions: We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism. Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects.

The effect of orally administered activated charcoal (AC) on the sleep times of mice following intravenous injection of various hypnotics was investigated. Preliminary studies with phenobarbital (Pb) showed that a linear relationship exists between the Pb-induced sleep time and the logarithm of the Pb dose in both control and AC treated mice. Half-lives of Pb in the two groups were estimated to be 8.1 and 0.9 h, respectively. A linear decline in Pb-induced sleep time with increasing dose of AC was observed up to a maximum effective dose of AC beyond which dose increments caused no further reduction in sleep time. A similar relationship was observed between sleep time and the concentration of sodium sulfate in which the AC was suspended. AC treatment resulted in an 82-88 per cent reduction in sleep time induced by administration of phenobarbital, methyprylon, glutethimide, ethchlorvynol, and methaqualone. AC had no significant effect on sleep time following amobarbital or pentobarbital administration.

We studied the association between the movement of operating room personnel and bacterial contamination of the operative field during 12 clean operations. Settle plates placed on the patient's chest and instrument table were exposed during the operation. As a control, settle plates were exposed in the same locations when no personnel and patients were in the room. Bacterial contamination of the aseptic field was categorized as disseminating (Group A: greater than 42 combined movements) and nondisseminating (Group B: less than 42 combined movements). There were 24 persons in each group. There was a highly significant difference between the two groups in the colony counts on settling plates. More vigorous movement was associated with increased bacterial contamination of the operative field. Low bacterial colony counts were found in the control plates, ruling out environmental sources of contamination. Bacterial fallout correlated with the movement of personnel. Measures to reduce excessive movement in the OR are recommended.

The present study examined the prescription practices concerning psychotropic drugs in 5 major oncology centers over a 6 month period. During the survey period 1579 patients were admitted to the collaborating institutions, and 51% of them were prescribed at least one psychotropic medication. Hypnotics were the most frequently prescribed drugs, accounting for 48% of total prescriptions, followed by anti-psychotics at 26% and anti-anxiety agents at 25%. Anti-depressant drugs accounted for only 1% of psychotropic prescriptions. Analysis of prescription rationales revealed that 44% of the psychotropic prescriptions were written for sleep, while 25% were given for nausea and vomiting; approximately 17% were attributed to psychological distress, and 12% were associated with diagnostic medical procedures. The overall rate of prescription was approximately 2 psychotropic drugs per patient per admission, with only 2% of prescriptions resulting in chart-documented side effects. At the level of individual compounds, 3 distinct drugs accounted for 72% of total prescriptions--flurazepam (33%), prochlorperazine (21%), and diazepam (17%).