French Sleepiness Scale for Adolescents-8 items: A discriminant and diagnostic validation.

The objective of the present study was to validate the Short Version of French Sleepiness Scale for Adolescents (FSSA) with eight items (FSSA8). METHODS: A total of 384 adolescents, aged between 12 and 18 years, completed the FSSA8. These included 269 nonclinical adolescents and 115 adolescents admitted for overnight polysomnography and Multiple Sleep Latency Test (MSLT) because of suspected hypersomnia (85 patients with narcolepsy and 30 with other sleep disorders). Item response theory (IRT) assumptions were tested and psychometric properties were analysed. Matching on sex ratio and age was conducted to estimate concurrent criterion, diagnostic validity and cut-offs. RESULTS: IRT assumptions were validated confirming the one-dimensionality of the FSSA8. The latent continuum sleepiness for which the scale and its items are reliable encompassed most of the clinical subjects. FSSA8 is weakly correlated with MSLT. Distribution of scores for the nonclinical group and the clinical group differed significantly; the FSSA8 had very good screening validity in sleep disorders. The cut-off was seven points. CONCLUSION: The FSSA8 appeared to be more reliable for patients than for nonclinical participants and to be a good tool for screening excessive daytime sleepiness in sleep disorders.

[Hemophagocytic lymphohistiocytosis on Epstein-Barr Virus reactivation]. / Lymphohistiocytose hémophagocytaire sur réactivation de l'Epstein-Barr Virus.

We describe the case of a 43-years-old female patient admitted in the emergency department for impairment of general condition and dyspnea. This patient is on immunosuppressive medication for Behçet's disease and will develop a lymphoma and hemophagocytic lymphohistiocytosis following Epstein-Barr virus (EBV) reactivation. This clinical case introduces a brief literature review about hemophagocytic lymphohistiocytosis (HLH).

Nous présentons le cas d'une patiente âgée de 43 ans se présentant aux urgences pour altération de l'état général et pour dyspnée. Cette patiente est sous immunosuppresseurs dans le cadre d'une maladie de Behçet et va développer un lymphome ainsi qu'une lymphohistiocytose hémophagocytaire suite à une réactivation de l'Epstein- Barr Virus (EBV). Ce cas clinique permet de présenter une brève revue de littérature sur la lymphohistiocytose hémophagocytaire (LHH).

SIMMEON-Prep study: SIMulation of Medication Errors in ONcology: prevention of antineoplastic preparation errors.

WHAT IS KNOWN AND OBJECTIVE: Medication errors (ME) in oncology are known to cause serious iatrogenic complications. However, MEs still occur at each step in the anticancer chemotherapy process, particularly when injections are prepared in the hospital pharmacy. This study assessed whether a ME simulation program would help prevent ME-associated iatrogenic complications. METHODS: The 5-month prospective study, consisting of three phases, was undertaken in the centralized pharmaceutical unit of a university hospital of Lyon, France. During the first simulation phase, 25 instruction sheets each containing one simulated error were inserted among various instruction sheets issued to blinded technicians. The second phase consisted of activity aimed at raising pharmacy technicians' awareness of risk of medication errors associated with antineoplastic drugs. The third phase consisted of re-enacting the error simulation process 3 months after the awareness campaign. The rate and severity of undetected medication errors were measured during the two simulation (first and third) phases. The potential seriousness of the ME was assessed using the NCC MERP(®) index. RESULTS AND DISCUSSION: The rate of undetected medication errors decreased from 12 in the first simulation phase (48%) to five in the second simulation phase (20%, P = 0.04). The number of potential deaths due to administration of a faulty preparation decreased from three to zero. Awareness of iatrogenic risk through error simulation allowed pharmacy technicians to improve their ability to identify errors. WHAT IS NEW AND CONCLUSION: This study is the first demonstration of the successful application of a simulation-based learning tool for reducing errors in the preparation of injectable anticancer drugs. Such a program should form part of the continuous quality improvement of risk management strategies for cancer patients.

Using bone marrow matrix to analyze meprobamate for forensic toxicological purposes.

Bone marrow (BM) analysis is of forensic interest for postmortem toxicological investigations where blood samples are unavailable or unusable. Due to the lack of studies, it remains difficult to interpret concentrations of xenobiotics measured in this matrix. Based on a statistical approach published previously to interpret meprobamate concentrations in bile and vitreous humor, we propose here a diagnostic test for interpretation of BM meprobamate concentrations from analysis of 99 sets of autopsy data. The mean age was 48 years (range 18-80 years, one unknown) for males and 50 years (range 19-80 years, one unknown) for females, with a male/female ratio at 0.768. A BM concentration threshold of 11.3 µg/g was found to be statistically equivalent to that of a blood meprobamate concentration threshold of 50 µg/ml in distinguishing overdose from therapeutic use. The intrinsic qualities of this diagnostic test were good with sensitivity of 0.82 and specificity of 0.92. Compared to previous tests published with the same objective on vitreous humor and bile, this study shows that BM is a useful alternative matrix to reveal meprobamate overdose when blood, vitreous humor, and bile are not available or unusable.

Development, testing, and deployment of an air sampling manifold for spiking elemental and oxidized mercury during the Reno Atmospheric Mercury Intercomparison Experiment (RAMIX).

The Reno Atmospheric Mercury Intercomparison Experiment (RAMIX) was in Reno, NV from August 22, 2011 to September 16, 2011. The goals of the experiment were to compare existing and new methods for measurements of ambient elemental and oxidized Hg, and to test these with quantitative spikes of Hg(0), HgBr2, O3 and water vapor. In this paper we describe the design, testing, and deployment of a high flow manifold system designed to deliver ambient air and spiked compounds to multiple instruments simultaneously. The manifold was constructed of 1" OD PFA tubing and heated to 115 °C for the entire active zone. Manifold flow was controlled at ∼200 LPM using a blower and a velocity sensor in a feedback control system. Permeation tubes in controlled ovens were used to deliver Hg(0) and HgBr2. Ozone was generated from a small UV lamp in a flow of high purity O2. Water vapor was generated by pumping a flow of purified N2 through heated, high purity water. The spiking delivery for Hg(0), HgBr2, O3, and water vapor after dilution in the manifold ranged up to 20 ng m(-3), 0.64 ng m(-3), 100 ppbv, and 20 g kg(-1), respectively. During laboratory tests the average transmission efficiencies for Hg(0), HgBr2, and O3 were found to be 92%, 76%, and 93%, respectively.

In vitro orthodontic bracket bonding to porcelain.

This in vitro study investigated the influence of using different combinations of bracket, adhesive, and light-curing source on the tensile bond strength to porcelain and on failure patterns at debonding. Tensile tests were performed using: one ceramic bracket versus one metal bracket, two orthodontic composites; type bisphenol A-glycidyldimethacrylate and urethane dimethacrylate (UDMA), and four light-curing units with the same range of emission spectrum but various light intensities: three light-emitting diode (LED) units and one halogen-based unit. One hundred and sixty porcelain samples were randomly divided into 16 equal groups. The porcelain surface was conditioned with 9 per cent hydrofluoric acid before silane application. The composite was photo-polymerized for 40 seconds. After storage in water at 37°C for 24 hours, the samples were subjected to tensile force until bond failure. Bond strength and bond failure mode were recorded; results were analysed (α = 0.05) using R language; linear model with constant variance for the bond strength and multinomial distribution for the failure mode. The bond strength in all groups was sufficient to withstand orthodontic treatment (>6 MPa). There was no statistical difference between the adhesives, but comparing bracket × light interaction, it was significantly higher with the ceramic bracket. No significant differences were seen between the metal bracket groups, but for the ceramic bracket, the results were significantly higher with the LED light. No fracture was observed in porcelain with the metal bracket but it occurred in 35 per cent of the ceramic bracket samples and the risk was higher when using UDMA composite and lower with LED high intensity light.

Scaling non-point-source mercury emissions from two active industrial gold mines: influential variables and annual emission estimates.

Open-pit gold mines encompass thousands of hectares of disturbed materials that are often naturally enriched in mercury (Hg). The objective of this study was to estimate annual non-point-source Hg emissions from two active gold mines in Nevada. This was achieved by measuring diel and seasonally representative Hg fluxes from mesocosms of materials collected from each mine. These measurements provided a framework for scaling emissions over space and time at each mine by identifying the important variables correlated with Hg flux. The validity of these correlations was tested by comparisons with measurements conducted in situ at the mines. Of the average diel fluxes obtained in situ (92 daily flux measurements), 81% were within the 95% prediction limits of the regressions developed from the laboratory-derived data. Some surfaces at the mines could not be simulated in the laboratory setting (e.g., material actively leached by cyanide solution and tailings saturated with cyanide solution), and as such in situ data were applied for scaling. Based on the surface areas of the materials and environmental conditions at the mines during the year of study, non-point-source Hg releases were estimated to be 19 and 109 kg·year(-1). These account for 56% and 14%, respectively, of the overall emissions from each mine (point + nonpoint sources). Material being heap-leached and active tailings impoundments were the major contributors to the releases (>60% combined) suggesting that as mining operations cease, releases will decline.

Osmotic stress and the yeast cytoskeleton: phenotype-specific suppression of an actin mutation.

In the yeast Saccharomyces cerevisiae, actin filaments function to direct cell growth to the emerging bud. Yeast has a single essential actin gene, ACT1. Diploid cells containing a single copy of ACT1 are osmosensitive (Osms), i.e., they fail to grow in high osmolarity media (D. Shortle, unpublished observations cited by Novick, P., and D. Botstein. 1985. Cell. 40:415-426). This phenotype suggests that an underlying physiological process involving actin is osmosensitive. Here, we demonstrate that this physiological process is a rapid and reversible change in actin filament organization in cells exposed to osmotic stress. Filamentous actin was stained using rhodamine phalloidin. Increasing external osmolarity caused a rapid loss of actin filament cables, followed by a slower redistribution of cortical actin filament patches. In the recovery phase, cables and patches were restored to their original levels and locations. Strains containing an act1-1 mutation are both Osms and temperature-sensitive (Ts) (Novick and Botstein, 1985). To identify genes whose products functionally interact with actin in cellular responses to osmotic stress, we have isolated extragenic suppressors which revert only the Osms but not the Ts phenotype of an act1-1 mutant. These suppressors identify three genes, RAH1-RAH3. Morphological and genetic properties of a dominant suppressor mutation suggest that the product of the wild-type allele, RAH3+, is an actin-binding protein that interacts with actin to allow reassembly of the cytoskeleton following osmotic stress.

A mechanosensitive ion channel in the yeast plasma membrane.

Mechanosensitive ion channels use mechanical energy to gate the dissipation of electrochemical gradients across cell membranes. This function is fundamental to physiological processes such as hearing and touch. In electrophysiological studies of ion channels in the plasma membrane of the yeast Saccharomyces cerevisiae, channels were observed that were activated by, and adapted to, stretching of the membrane. Adaptation of channel activity to mechanical stimuli was voltage-dependent. Because these mechanosensitive channels pass both cations and anions, they may play a role in turgor regulation in this walled organism.

An osmosensing signal transduction pathway in yeast.

Yeast genes were isolated that are required for restoring the osmotic gradient across the cell membrane in response to increased external osmolarity. Two of these genes, HOG1 and PBS2, encode members of the mitogen-activated protein kinase (MAP kinase) and MAP kinase kinase gene families, respectively. MAP kinases are activated by extracellular ligands such as growth factors and function as intermediate kinases in protein phosphorylation cascades. A rapid, PBS2-dependent tyrosine phosphorylation of HOG1 protein occurred in response to increases in extracellular osmolarity. These data define a signal transduction pathway that is activated by changes in the osmolarity of the extracellular environment.

Ion channels in yeast.

Voltage-dependent ion channels have been found in the plasma membrane of the yeast Saccharomyces cerevisiae. Ion channel activities were recorded from spheroplasts or patches of plasma membrane with the patch-clamp technique. The most prominent activities came from a set of potassium channels with the properties of activation by positive but not negative voltages, high selectivity for potassium over sodium ion, unit conductance of 20 picosiemens, inhibition by tetraethylammonium or barium ions, and bursting kinetics.

Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in bile.

Investigating toxicological causes of death may require alternative matrices when the usual ones are lacking. Whereas forensic toxicology uses bile almost only for xenobiotic screening, a diagnostic test interpreting postmortem bile concentrations of meprobamate is reported. Based on 128 sets of autopsy data, its intrinsic qualities were good, with 0.95 sensitivity and 0.93 specificity. In a French forensic population, the positive and negative predictive factors were 0.90 and 0.97, respectively. It is a useful means of revealing overdoses where blood samples are not available or of confirming blood tests when postmortem redistribution is suspected.

[An unusual interstitial pneumonitis]. / Une pneumopathie interstitielle inhabituelle.

We report the case of a twenty-six-years-old patient who developed acute silicosis after only five years of professional exposure. He also succeedingly presented in the course of the disease progressive massive fibrosis, rest hypoxia, and eventually spontaneous pneumothorax. Monopulmonary transplantation was finally successfully performed.

MAP kinase pathways in the yeast Saccharomyces cerevisiae.

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

Prospective survey of azole drug resistance among environmental and clinical isolates of Aspergillus fumigatus in a French University hospital during major demolition works.

OBJECTIVES: Recent studies have reported the emerging worldwide problem of azole drug resistance of A. fumigatus isolates. The aim of this study was to evaluate the antifungal susceptibilities of A. fumigatus isolates recovered from air and clinical samples collected in a French University hospital (Lyon), which underwent major deconstruction works over a one year-period. METHODS: A daily surveillance of fungal contamination was implemented during 11-months. Environmental survey was realized by air samplings, outdoor and indoor, with an automatic agar sampler. In parallel, surveillance of IA infection cases was conducted by epidemiological investigation. Environmental and clinical isolates of A. fumigatus were identified by conventional methods and ß-tubulin sequencing. Susceptibility testing of A. fumigatus isolates against Itraconazole (ITZ), Voriconazole (VCZ) was performed using Etest method. RESULTS: A total of 3885 air samples (1744 outdoor samples and 2141 indoor samples) were collected. From the 3073 identified colonies of A. fumigatus, 400 A. fumigatus isolates were tested for their susceptibility to ITZ and VCZ, including 388 isolates coming from the environment (indoor n:157, outdoor n:231) and 12 isolates coming from clinical samples. All the 400 isolates were susceptible to azoles (≤1µg/mL). CONCLUSIONS: No environmental reservoir of A. fumigatus azole resistant strains was found in our hospital which was undergoing major demolition works. Further studies with larger number of A. fumigatus clinical isolates and environmental isolates from agricultural areas and healthcare establishments are needed to better appreciate the occurrence and prevalence of azole resistance.

The osmoregulatory pathway represses mating pathway activity in Saccharomyces cerevisiae: isolation of a FUS3 mutant that is insensitive to the repression mechanism.

Mitogen-activated protein (MAP) kinase cascades are conserved signal transduction pathways that are required for eukaryotic cells to respond to a variety of stimuli. Multiple MAP kinase pathways can function within a single cell type; therefore, mechanisms that insulate one MAP kinase pathway from adventitious activations by parallel pathways may exist. We have studied interactions between the mating pheromone response and the osmoregulatory (high-osmolarity glycerol response [HOG]) pathways in Saccharomyces cerevisiae which utilize the MAP kinases Fus3p and Hog1p, respectively. Inactivating mutations in HOG pathway kinases cause an increase in the phosphotyrosine content of Fus3p, greater expression of pheromone-responsive genes, and increased sensitivity to growth arrest by pheromone. Therefore, the HOG pathway represses mating pathway activity. In a HOG1+ strain, Fus3p phosphotyrosine increases modestly and transiently following an increase in the extracellular osmolarity; however, it increases to a greater extent and for a sustained duration in a hog1-delta strain. Thus, the HOG-mediated repression of mating pathway activity may insulate the mating pathway from activation by osmotic stress. A FUS3 allele whose gene product is resistant to the HOG-mediated repression of its phosphotyrosine content has been isolated. This mutant encodes an amino acid substitution in the highly conserved DPXDEP motif in subdomain XI. Other investigators have shown that the corresponding amino acid is also mutated in a gain-of-function allele of the MAP kinase encoded by the rolled locus in Drosophila melanogaster. These data suggest that the DPXDEP motif plays a role in the negative regulation of MAP kinases.

Regulation of cell cycle progression by Swe1p and Hog1p following hypertonic stress.

Exposure of yeast cells to an increase in external osmolarity induces a temporary growth arrest. Recovery from this stress is mediated by the accumulation of intracellular glycerol and the transcription of several stress response genes. Increased external osmolarity causes a transient accumulation of 1N and 2N cells and a concomitant depletion of S phase cells. Hypertonic stress triggers a cell cycle delay in G2 phase cells that appears distinct from the morphogenesis checkpoint, which operates in early S phase cells. Hypertonic stress causes a decrease in CLB2 mRNA, phosphorylation of Cdc28p, and inhibition of Clb2p-Cdc28p kinase activity, whereas Clb2 protein levels are unaffected. Like the morphogenesis checkpoint, the osmotic stress-induced G2 delay is dependent upon the kinase Swe1p, but is not tightly correlated with inhibition of Clb2p-Cdc28p kinase activity. Thus, deletion of SWE1 does not prevent the hypertonic stress-induced inhibition of Clb2p-Cdc28p kinase activity. Mutation of the Swe1p phosphorylation site on Cdc28p (Y19) does not fully eliminate the Swe1p-dependent cell cycle delay, suggesting that Swe1p may have functions independent of Cdc28p phosphorylation. Conversely, deletion of the mitogen-activated protein kinase HOG1 does prevent Clb2p-Cdc28p inhibition by hypertonic stress, but does not block Cdc28p phosphorylation or alleviate the cell cycle delay. However, Hog1p does contribute to proper nuclear segregation after hypertonic stress in cells that lack Swe1p. These results suggest a hypertonic stress-induced cell cycle delay in G2 phase that is mediated in a novel way by Swe1p in cooperation with Hog1p.

Air-soil exchange of mercury from background soils in the United States.

The air-surface exchange of mercury (Hg) was measured, using a dynamic polycarbonate flux chamber, for soils with low or "background" Hg concentrations (<0.1 mg/kg) at eleven locations across the contiguous United States. Sampling locations included agricultural, desert, grassland, mixed and pine forest ecosystems (n=1326 soil flux measurements at 46 individual sites). An overall soil Hg flux of 0.9+/-0.2 ng/m2/h for these background soils was obtained by averaging the means for the different locations. Soil Hg fluxes were significantly lower in dark conditions than in the light for all but the grassland sites. Mean inlet air Hg concentrations were 1.0+/-0.1 ng/m3 in the dark and 1.3+/-0.2 ng/m3 in the light. Soil temperature inside and outside of the chamber, air temperature, relative humidity, and irradiance were measured concurrently with soil Hg flux. Soil-air Hg exchange was weakly predicted by environmental variables (R2 from 0.07 to 0.52). For a single location, flux was better correlated with soil moisture than other measured environmental parameters, suggesting that soil moisture might be an important driver for Hg emissions from background soils. In addition, based on data collected we suggest some quality control measures for use of Tekran 2537A analyzers when measuring low mercury fluxes. Using basic scaling procedures, we roughly estimate that natural emissions from soils in the contiguous U.S. release approximately 100 Mg/yr of Hg to the atmosphere.

Mercury accumulation in grass and forb species as a function of atmospheric carbon dioxide concentrations and mercury exposures in air and soil.

The goal of this study was to investigate the potential for atmospheric Hg degrees uptake by grassland species as a function of different air and soil Hg exposures, and to specifically test how increasing atmospheric CO(2) concentrations may influence foliar Hg concentrations. Four common tallgrass prairie species were germinated and grown for 7 months in environmentally controlled chambers using two different atmospheric elemental mercury (Hg major; 3.7+/-2.0 and 10.2+/-3.5 ng m(-3)), soil Hg (<0.01 and 0.15+/-0.08 micro g g(-1)), and atmospheric carbon dioxide (CO(2)) (390+/-18, 598+/-22 micro mol mol(-1)) exposures. Species used included two C4 grasses and two C3 forbs. Elevated CO(2) concentrations led to lower foliar Hg concentrations in plants exposed to low (i.e., ambient) air Hg degrees concentrations, but no CO(2) effect was apparent at higher air Hg degrees exposure. The observed CO(2) effect suggests that leaf Hg uptake might be controlled by leaf physiological processes such as stomatal conductance which is typically reduced under elevated CO(2). Foliar tissue exposed to elevated air Hg degrees concentrations had higher concentrations than those exposed to low air Hg degrees , but only when also exposed to elevated CO(2). The relationships for foliar Hg concentrations at different atmospheric CO(2) and Hg degrees exposures indicate that these species may have a limited capacity for Hg storage; at ambient CO(2) concentrations all Hg absorption sites in leaves may have been saturated while at elevated CO(2) when stomatal conductance was reduced saturation may have been reached only at higher concentrations of atmospheric Hg degrees . Foliar Hg concentrations were not correlated to soil Hg exposures, except for one of the four species (Rudbeckia hirta). Higher soil Hg concentrations resulted in high root Hg concentrations and considerably increased the percentage of total plant Hg allocated to roots. The large shifts in Hg allocation patterns-notably under soil conditions only slightly above natural background levels-indicate a potentially strong role of plants in belowground Hg transformation and cycling processes.

Neomycin inhibits the calcium current of Paramecium.

The duration of high-K+ stimulated backward swimming is a commonly used bioassay for estimating the amplitude of the inward calcium current of Paramecium. Electrophysiological analysis confirmed that concentrations of neomycin which decreased the duration of stimulated backward swimming also reduced the isolated inward calcium current. Other polycations were also effective in this bioassay and their effectiveness was correlated with the number of their positive charges. Paramecium is therefore a convenient model system for studying the effects of compounds such as neomycin on calcium currents as well as their mechanisms of action.