Occupational asthma.

Work-related asthma is highly prevalent and represents a significant societal and financial burden worldwide. This State of the Art series article explores the epidemiology, clinical features, diagnosis and management of occupational asthma (OA), which comprises sensitiser-induced asthma and irritant-induced asthma (IIA). Sensitiser-induced OA is the development of asthma through sensitisation to a substance in the workplace. OA is largely underdiagnosed, and its clinical manifestations are non-specific, which makes its diagnosis challenging. Early and accurate diagnosis of OA through comprehensive testing is primordial to avoid unwarranted removal from exposure and to allow early management of confirmed cases. Despite optimal management, up to 70% of patients with OA will have persistent asthma several years after diagnosis. IIA classically refers to the development of de novo asthma acutely following an intense exposure to an irritant agent. However, some cases of IIA following multiple high-level exposures or a chronic low-dose exposure have been reported.

2H-enrichment of cellulose and n-alkanes in heterotrophic plants.

Hydrogen (H) isotopes of plant organic compounds are rarely employed in ecological studies. If so, these values are interpreted as being indicative of the plant source and/or leaf water. Recent observations suggest, however, that variations in hydrogen isotope fractionation that occur during the biosynthesis of plant compounds (2H-εbio) imprint valuable metabolic information into the hydrogen isotope composition (δ2H values) of plant organic compounds. Here we show a consistent 2H-enrichment of compounds in heterotrophically growing plants across a series of autotrophic/heterotrophic plant pairs. We suggest that this is due to a higher recycling of compounds in the Calvin and tricarboxylic acid cycles in heterotrophic plants that is associated with a more complete exchange of C-bound H with the surrounding 2H-enriched foliar water. Interestingly, we found that 2H-enrichment in heterotrophic plants was larger for carbohydrates than for lipids, with an average 2H-enrichment of 76 ± 9‰ in α-cellulose and 23 ± 23‰ in n-alkanes. We propose that this systematically larger 2H-enrichment for carbohydrates than for lipids is either due to different level of 2H-fractionation associated with heterotrophically produced NADPH, or to the potential uptake of lipids by heterotrophic plants. With the work we present here, we contribute to a better mechanistic understanding of what the biochemical principles are that couple the carbohydrate dynamics of plants to their δ2H values and hope to foster as such the application of H isotopes in plant sciences.

SA-SSR: a suffix array-based algorithm for exhaustive and efficient SSR discovery in large genetic sequences.

UNLABELLED: Simple Sequence Repeats (SSRs) are used to address a variety of research questions in a variety of fields (e.g. population genetics, phylogenetics, forensics, etc.), due to their high mutability within and between species. Here, we present an innovative algorithm, SA-SSR, based on suffix and longest common prefix arrays for efficiently detecting SSRs in large sets of sequences. Existing SSR detection applications are hampered by one or more limitations (i.e. speed, accuracy, ease-of-use, etc.). Our algorithm addresses these challenges while being the most comprehensive and correct SSR detection software available. SA-SSR is 100% accurate and detected >1000 more SSRs than the second best algorithm, while offering greater control to the user than any existing software. AVAILABILITY AND IMPLEMENTATION: SA-SSR is freely available at http://github.com/ridgelab/SA-SSR CONTACT: perry.ridge@byu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clostridium difficile O27 colitis: hospital-onset but community-acquired.

Large outbreaks of Clostridium difficile (CD) associated colitis in North America and Europe have been attributed to the emergence of the epidemic/toxin PCR Ribotype O27 CD strain (CD027). Due to the increased virulence of this epidemic strain and its propension for causing outbreaks, we performed a structured risk-assessment approach in order to determine the risks associated with the introduction of this strain within our university hospital. From February 2009 to January 2010, we identified 31 cases of CD027 associated colitis, whereby twenty one (67.7%) had symptoms onset more than 48 hours after admission and were classified as nosocomial. These patients had received wide-spectrum antimicrobials for other infections in the hospital before CD027 colitis diagnosis. The 31 patients with CD027 were admitted in 20 different units, managed by distinct health-care workers (HCWs), and no contact was identified between patients during their hospital stay. Furthermore, infection control audits showed 100% compliance with institutional guidelines for control of CD colitis. These findings suggest that CD027 is most frequently acquired in the community and emerges sporadically under antibiotic pressure during hospitalization.

Femtosecond laser excitation of spin resonances in amorphous ferrimagnetic Gd(1-x)Co(x) alloys.

Using 100 fs laser pulses, a high-frequency exchange and a low-frequency ferromagnetic resonance mode have been excited and detected in an amorphous Gd(1-x)Co(x) (78≤x≤85) ferrimagnetic thin film, on both sides of its angular momentum compensation composition. The excitation efficiency of these modes strongly depends on the amount of laser-induced heating. Ways of selectively and efficiently exciting either one or both of these two coexisting magnetic modes by adjusting laser pulse intensity are demonstrated.

Effect of higher minimum inhibitory concentrations of quaternary ammonium compounds in clinical E. coli isolates on antibiotic susceptibilities and clinical outcomes.

Quaternary ammonium compounds (QACs) are cationic surfactants used as preservatives and environmental disinfectants. Limited data are available regarding the effect of QACs in the clinical setting. We performed a prospective cohort study in 153 patients with Escherichia coli bacteraemia from February to September 2008 at University Hospital in Rennes. The minimum inhibitory concentrations (MICs) of antibiotics and QACs alkyldimethylbenzylammonium chloride (ADBAC) and didecyldimethylammonium chloride (DDAC) were determined by the agar dilution method. The capacity of biofilm production was assayed using the Crystal Violet method, and mutation frequencies by measuring the capacity of strains to generate resistance to rifampicin. Logistic regression analysis showed that one of the significant factors related to low MICs for ADBAC (≤16 mg/L) and DDAC (≤8 mg/L), was cotrimoxazole susceptibility (odds ratio: 3.72; 95% confidence interval: 1.22-11.24; P=0.02 and OR: 3.61; 95% CI: 1.56-7.56; P<0.01, respectively). Antibiotic susceptibility to cotrimoxazole was strongly associated with susceptibility to amoxicillin and nalidixic acid (P<0.01). Community-acquired or healthcare-associated bacteraemia, severity of bacteraemia, and patient outcome were independent of the MICs of ADBAC and DDAC. Our findings demonstrate an epidemiological relationship between higher MIC values of QACs in clinical E. coli isolates and antibiotic resistance.

Impact of surgical site infection surveillance in a neurosurgical unit.

This article describes a two-year surveillance of neurosurgical site infections and an outbreak of infections in deep brain stimulation (DBS) cases. From April to December 2008, six patients had a DBS surgical site infection (SSI). Audits of hygiene practices, infection control of the healthcare environment, and preoperative antimicrobial prophylaxis characteristics were carried out. The results of surgical audits showed that skin preparation and antimicrobial prophylaxis were not being performed adequately. In 2008, the general SSI rate was 1.8% (27 SSIs/1471 patients). Length of preoperative stay was significantly longer among infected patients (2.7 ± 2.9 months) compared with uninfected patients (2.2 ± 4.6 months) (P=0.01). Based on these results, skin preparation and antimicrobial prophylaxis were reviewed with the neurosurgery team. In 2009, the general SSI rate was reduced to 1.1% (16 SSI in 1410 patients), a reduction from 2008 (P=0.12). Although the overall incidence of SSI in 2008 (1.8%) was within the range of published data, this surveillance of SSIs permitted identification of site operative infected patients surgically treated for DBS. A set of actions was then taken to reduce SSI risk. This work demonstrates how an active surveillance programme can successfully change clinical care practice.

Influence of job seniority, hand hygiene education, and patient-to-nurse ratio on hand disinfection compliance.

Hand hygiene compliance was evaluated by direct observation in 2006 and 2007. In 2007, data on characteristics such as job seniority, hand hygiene education, and patient-to-nurse ratio during direct observations were collected. A hand hygiene promotional programme was performed between the two evaluations. Univariate and multivariate analysis identified factors associated with improved hand hygiene compliance. Between 2006 and 2007, from 761 hand hygiene opportunities, overall and partial compliance improved from 44.9% to 58% (P<0.001) and from 73.5% to 88.4% (P<0.001), respectively. In 2007, improvements in hand hygiene overall or partial compliance were seen when senior healthcare workers (HCWs) were present in the clinical area under investigation (P=0.04 or P=0.08, respectively). Partial hand hygiene compliance was significantly better in 2007 after a hand hygiene educational programme had been presented (P<0.015). Similar rates of compliance were observed whatever the patient-to-nurse ratio during the observation. Multivariate analysis identified job seniority as an independent predictor of hand hygiene compliance. Our results suggest that hand hygiene compliance is influenced by education on hand hygiene and that a senior HCW could act as a role model for other HCWs. These data should be considered when developing future hygiene interventions.

Outbreak of Serratia marcescens in a neonatal intensive care unit: contaminated unmedicated liquid soap and risk factors.

This study describes an outbreak of Serratia marcescens and its investigation and control in a neonatal intensive care unit (NICU). During a three-month period, five infants were colonised or infected by a single strain of S. marcescens. A case-control study, culture surveys and pulse-field gel electrophoresis analysis implicated a bottle soap dispenser as a reservoir of S. marcescens (P=0.032). Infants with S. marcescens colonisation or infection were also more likely to have been exposed to a central or percutaneous venous catheter (P=0.05) and had had longer exposure to endotracheal intubation (P=0.05). Soap dispensers are used in many hospitals and may be an unrecognised source of nosocomial infections. This potential source of infection could be reduced by using 'airless' dispensers which have no air intake for the distribution of soap. Prompt intervention and strict adherence to alcoholic hand disinfection were the key factors that led to the successful control of this outbreak.

High resolution polar Kerr magnetometer for nanomagnetism and nanospintronics.

A new high resolution polar magneto-optical (MO) Kerr magnetometer, devoted to the study of nanometer sized elements with perpendicular magnetic anisotropy, is described. The unique performances of this setup in terms of sensitivity (1.2x10(-15) emu), stability (lateral drift +/-35 nm over 3 h), and resolution (laser spot full width at half maximum down to 470 nm) are demonstrated, and illustrated by Kerr hysteresis loop measurements on a unique ultrathin magnetic nanodot, and over small segments of ultranarrow magnetic tracks. Large scanning MO Kerr microscopy images were also obtained with the same performances.

Creep and flow regimes of magnetic domain-wall motion in ultrathin Pt/Co/Pt films with perpendicular anisotropy.

We report on magnetic domain-wall velocity measurements in ultrathin Pt/Co(0.5-0.8 nm)/Pt films with perpendicular anisotropy over a large range of applied magnetic fields. The complete velocity-field characteristics are obtained, enabling an examination of the transition between thermally activated creep and viscous flow: motion regimes predicted from general theories for driven elastic interfaces in weakly disordered media. The dissipation limited flow regime is found to be consistent with precessional domain-wall motion, analysis of which yields values for the damping parameter, alpha.

Virulence of viable but nonculturable S. Typhimurium LT2 after peracetic acid treatment.

S. Typhimurium LT2 cells suspended in sterilized sewage effluent water (SEW) and in distilled water microcosms were exposed to 0, 7, 15 and 20 mg/l peracetic acid, and tested for viability and virulence. After treatment for one hour, colony forming units decreased by at least 5 log units at peracetic acid concentration of 7 mg/l. In SEW, at peracetic acid concentration of 15 mg/l, the cells were nonculturable (VNC), but retained virulence as demonstrated by invasion assays of HeLa cells. Higher concentrations (greater than or equal to 20 mg/l) resulted in bacterial death, i.e. substrate non-responsive cells. Despite morphological alterations of the bacteria after peracetic acid treatment, visualized by transmission electronic microscopy, conservation of both adhesive and invasive capacities was confirmed by scanning electron microscopy after exposure to 0-15 mg/l peracetic acid. Public health professionals need to recognize that peracetic acid-treated Salmonella is capable of modifying its physiological characteristics, including entering and recovering from the viable but nonculturable state, and may remain virulent after a stay in SEW followed by peracetic acid treatment.

Influence of peracetic acid on adhesion/invasion of Salmonella enterica serotype typhimurium LT2.

The influence of peracetic acid (PAA) disinfectant on Salmonella enterica serotype Typhimurium LT2 in sewage effluent was examined by studying its ability to adhere to and invade HeLa cells in vitro. Although the disinfectant produced a decrease of about 5 log units, the bacteria kept their adhesive and invasive abilities. Scanning microscopic observations of the PAA-treated bacteria revealed that PAA caused a loss of external microfilaments and an alteration of membrane structure. Nevertheless, electron-microscopic observations showed that PAA-treated bacteria were still able to adhere to and invade HeLa cells despite the fact that the bacteria seemed to have undergone some structural modifications. With confocal microscopy, the use of anti-actin antibody showed that the contact between the bacteria (with or without PAA treatment) and the HeLa cells activated actinopolymerization of the HeLa cell cytoskeleton.

Osmotic stress-induced genetic rearrangements in Escherichia coli H10407 detected by randomly amplified polymorphic DNA analysis.

Randomly amplified polymorphic DNA (RAPD) analysis is a DNA polymorphism assay commonly used for fingerprinting genomes. After optimizing the reaction conditions, samples of Escherichia coli H10407 DNA were assayed to determine the influence of osmotic and/or oligotrophic stress on variations in RAPD banding patterns. Genetic rearrangements or DNA topology variations could be detected as changes in agarose gel electrophoresis banding profiles. A new amplicon generated using DNA extracted from bacteria prestarved by an osmotic stress and resuscitated in rich medium was observed. Enrichment improved recovery of mutator cells and allowed them to be detected in samples, suggesting that DNA modifications, such as stress-induced alterations and supercoiling phenomena, should be taken into consideration before beginning RAPD analyses.

In vitro susceptibilities of Capnocytophaga isolates to beta-lactam antibiotics and beta-lactamase inhibitors.

The susceptibilities of 43 pharyngeal isolates of Capnocytophaga to beta-lactam antibiotics, alone or in combination with beta-lactamase inhibitors, were tested by an agar dilution method. The 34 beta-lactamase-positive strains were highly resistant to beta-lactams, but the intrinsic activities of clavulanate, tazobactam, and sulbactam against Capnocytophaga, even beta-lactamase producers, indicates that these beta-lactamase inhibitors could be used for empirical treatment of neutropenic patients with oral sources of infection.

Proteins variations in Listeria monocytogenes exposed to high salinities.

Listeria monocytogenes Scott A grown in the minimal chemically defined medium M6LT was challenged to a concentration of either 35 or 65 g l(-1) of NaCl for 1 h in the presence of a [35S]cysteine-[35S]methionine labelling mix. The protein patterns were analysed by 2D-electrophoresis in the two conditions and isoosmotic condition (5 g l(-1) of NaCl in M6LT). A great number of proteins which were synthesized under isoosmotic conditions were either completely repressed or expressed at a reduced level, at 65 g l(-1) and to a lesser extent at 35 g l(-1) of NaCl. At 35 g l(-1) of NaCl, six proteins were up-regulated, five proteins showed no change in expression level and five were repressed. Among the proteins up-regulated at 35 g l(-1) of NaCl, a single one (18.7 kDa, pI 5.05) was up-regulated at 65 g l(-1) too. We observed 21 proteins which were repressed at 65 g l(-1) of NaCl, among which 11 completely disappeared. Some of the up-regulated proteins have characteristics of molecular weight and isoelectric point close to those of stress proteins reported elsewhere: the protein induced both at 35 and 65 g l(-1) might correspond to a previously proposed universal stress protein of Listeria. Some proteins which were repressed at 65 g l(-1) have molecular weights close to those of virulence proteins.

Effect of transdermal iontophoresis codelivery of hydrocortisone on metoclopramide pharmacokinetics and skin-induced reactions in human subjects.

The effects of transdermal iontophoresis (IP) codelivery of hydrocortisone (HC) on metoclopramide hydrochloride (MCP) pharmacokinetics and on skin-induced reactions were evaluated in a randomized, crossover clinical study. MCP, an antiemetic, low molecular weight, cationic drug intended for systemic delivery, was delivered from the anode of IP systems at a constant current of 100 microA/cm(2). HC, a neutral endogenous antiinflammatory agent, was codelivered from the same electrode, primarily by electroosmotic processes. Each subject (n = 7) wore two identical IP systems (MCP alone or MCP plus HC), each supplying 500 microA, one on each upper arm for 4 h. One week later, each subject repeated the procedure with the alternate type of MCP system. HC did not change the pharmacokinetics of MCP: There were no statistically significant differences in MCP plasma concentrations, half-life, area under the curve (AUC), or rate of absorption between the two treatment groups. However, HC significantly decreased erythema and edema scores produced by the IP of MCP. In both groups, a steady-state MCP flux of about 100 microg/(cm(2) x h) was achieved after only 1 h of transport, and input rate dropped dramatically immediately after removal of the system. In vitro, HC flux through human epidermis from an MCP plus HC formulation was 2.8 +/- 1.1 microg/(cm(2) x h) after 4 h transport at 100 microA/cm(2), suggesting negligible systemic exposure to hydrocortisone. These data indicate that MCP input rate and its clearance from the skin are unaltered by HC and that the codelivery of HC by IP is an effective strategy for inhibition of local reactions resulting from the transdermal delivery of drugs.

Nanomolar levels of dimethylsulfoniopropionate, dimethylsulfonioacetate, and glycine betaine are sufficient to confer osmoprotection to Escherichia coli.

We combined the use of low inoculation titers (300 +/- 100 CFU/ml) and enumeration of culturable cells to measure the osmoprotective potentialities of dimethylsulfoniopropionate (DMSP), dimethylsulfonioacetate (DMSA), and glycine betaine (GB) for salt-stressed cultures of Escherichia coli. Dilute bacterial cultures were grown with osmoprotectant concentrations that encompassed the nanomolar levels of GB and DMSP found in nature and the millimolar levels of osmoprotectants used in standard laboratory osmoprotection bioassays. Nanomolar concentrations of DMSA, DMSP, and GB were sufficient to enhance the salinity tolerance of E. coli cells expressing only the ProU high-affinity general osmoporter. In contrast, nanomolar levels of osmoprotectants were ineffective with a mutant strain (GM50) that expressed only the low-affinity ProP osmoporter. Transport studies showed that DMSA and DMSP, like GB, were taken up via both ProU and ProP. Moreover, ProU displayed higher affinities for the three osmoprotectants than ProP displayed, and ProP, like ProU, displayed much higher affinities for GB and DMSA than for DMSP. Interestingly, ProP did not operate at substrate concentrations of 200 nM or less, whereas ProU operated at concentrations ranging from 1 nM to millimolar levels. Consequently, proU(+) strains of E. coli, but not the proP(+) strain GM50, could also scavenge nanomolar levels of GB, DMSA, and DMSP from oligotrophic seawater. The physiological and ecological implications of these observations are discussed.

Pharmacokinetics, uses, and limitations of vancomycin-loaded bone cement.

We have studied the mechanical and pharmacokinetic characteristics of an industrially-prepared bone cement containing 3 g of vancomycin per 60 g cement. A low viscosity cement was selected, to increase contact between the antibiotic and the infected surfaces. Resistance of compression (95 mPa) was well above the required standard (70 mPa) and similar to that of other cements with or without gentamicin. The concentrations in blood, urine and bone were measured in mg/l and mg/kg, and compared to the break point (BP) of susceptibility tests, which must be obtained to achieve control of infection. Diffusion tests were conducted in vitro (elution in saline from rods), and in 30 sheep femora implanted with the cement in vivo. In the animal study, bone levels during the first three months were three-fold higher than the BP (i.e., were > or = 12 mg/l) in 92% of specimens from all areas of bone studied and at all times since implantation; they exceeded five times the BP in 56% of specimens and were never lower than twice the BP. The mean level was four times the BP after six months and fell sharply during the next six months. A pharmacokinetic study in ten patients who had a primary total hip arthroplasty with vancomycin-loaded cement as prophylactic antibiotic therapy showed that blood levels were lower than 3 micrograms/ml, i.e., 30 times lower than the toxic threshold (90 micrograms/ml). Vancomycin was undetectable in urine after the tenth day. The levels in drainage fluids were five times the BP after 24 h and equal to it after four days. None of the ten patients treated prophylactically with vancomycin-loaded cement developed evidence of allergy, toxicity, intolerance or loosening during a two year period. No adverse events were recorded in 17 other patients treated with a vancomycin (2 g) plus gentamicin (0.8 g) loaded cement as adjuvant therapy for severe prosthetic infection.