Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning.

Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knockout (KO) rats and AdipoQ KO mice using intravenous cocaine self-administration and conditioned place preference (CPP) paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/-) and KO (-/-) rats showed increased cue-induced reinstatement compared with wild-type (WT) rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 -/- rats showed higher responding for a saccharin reinforcer and learned the choice reaction time (RT) task more slowly than WTs. However, we found no differences between Cdh13 -/- and +/+ rats in responding for sensory reinforcement, number of premature responses in the RT task, tendency to approach a Pavlovian food cue, CPP and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ -/- mice, there was a significant increase in CPP to methamphetamine (1 mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.

Pedestal cleaning for high laser pulse contrast ratio with a 100 TW class laser system.

Laser matter interaction at relativistic intensities using 100 TW class laser systems or higher is becoming more and more widespread. One of the critical issues of such laser systems is to let the laser pulse interact at high intensity with the solid target and avoid any pre-plasma. Thus, a high Laser Pulse Contrast Ratio (LPCR) parameter is of prime importance. We present the LPCR characterization of a high repetition 100 TW class laser system. We demonstrate that the generated Amplified Spontaneous Emission (ASE) degrades the overall LPCR performance. We propose a simple way to clean the pulse after the first amplification stage by introducing a solid state saturable absorber which results in a LPCR improvement to better than 10(10) with only a 30% energy loss at a 10 Hz repetition rate. We finally correlated this cleaning method with experimental results.

Role of routine blood cultures in detecting unapparent infections during continuous renal replacement therapy.

OBJECTIVE: Continuous renal replacement therapy (CRRT) is frequently employed in the management of renal failure in unstable intensive care patients. At some centers, blood cultures are performed routinely while on CRRT to monitor for occult bacteremia. We questioned the role of routine blood cultures (RBC) in diagnosing underlying infections in these often afebrile patients. DESIGN: Retrospective cohort study (1998-2003). SETTING: Medical, surgical and pediatric intensive care units in a tertiary care teaching hospital. METHODS/MEASUREMENTS: We undertook a retrospective chart review of all 101 episodes of CRRT performed in our hospital since 1998. The primary endpoint of the study was the number of positive cultures that changed patient management. For each positive result, documented infection and parameters of sepsis were noted. RESULTS: There were 101 treatments of CRRT in 98 patients. A total of 698 routine RBC bottles were drawn, a mean of 7.2+/-7 per patient; of those, 29 (4%) were positive in 17patients, documenting 11 bacteremias. Six positive cultures represented contaminants. In all but one case, infection was known or signs of sepsis were present prior to receipt of the culture result. CONCLUSIONS: For patients on CRRT, RBC are rarely positive, and do not detect occult infection in the absence of clinical evidence of infection for the majority of patients. Because routine cultures utilize significant resources, and can result in false-positive results, RBC should not be performed in these patients. Careful clinical monitoring, with blood cultures performed at the first clinical suggestion of an infection, should detect all clinically relevant infections.

In vitro susceptibility study of BMS-284756 against Legionella species.

Legionella organisms are often associated with respiratory infections, and Legionella pneumonia results in significant mortality unless it is promptly and effectively treated. The present study was undertaken to compare the in vitro activity of BMS-284756 (T-3811ME), a novel des-F(6)-quinolone, against Legionella species versus the activity of other fluoroquinolones (levofloxacin, moxifloxacin, and ciprofloxacin) and of the macrolides erythromycin, clarithromycin, and azithromycin. The most potent agents tested against Legionella pneumophila serogroup 1, the largest group tested, were BMS-284756, moxifloxacin, and levofloxacin (MIC(90) = 0.016 mg/L). The MIC(90) range for BMS-284756 was 0.008-0.03 mg/L against the total panel of L pneumophila serogroups 1-9 and 12, with the lowest MIC(90) observed for serogroup 7 and the highest for serogroup 2. BMS-284756 was one of the most potent agents tested against isolates of L micdadei, L longbeachae, and other Legionella species (MIC(90) range: 0.008-0.06 mg/L). These results and the high intrinsic activity of BMS-284756 against other respiratory pathogens support its use as empiric monotherapy for a wide range of respiratory infections.

[Health professionals in part-time employment: the challenge of balancing work and family]. / Professionnelles de la santé en précarité d'emploi: le défi de la conciliation travail-famille.

Looking at the case of occasional part-time nurses, this study highlights the difficulties in balancing work and family that are inherent in nonstandard jobs. Eight focus groups were held, involving 48 nurses in 4 regions of Quebec. Analysis of the data collected reveals that nurses "on call" are particularly affected by overwork and experience great difficulty in balancing their work and family obligations. The participants proposed a variety of solutions, such as establishing day care centres adapted to the needs of nurses on call and instituting a timetable grid for occasional part-time nurses so that they can plan their work hours.

In vitro activity of ABT-773 versus macrolides and quinolones against resistant respiratory tract pathogens.

ABT-773, a novel ketolide, was compared to erythromycin, azithromycin, clarithromycin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin, and gemifloxacin against antibiotic-resistant strains recently isolated from patients with respiratory tract infections. MICs were determined by agar dilution using standard NCCLS methodology. ABT-773 (MIC(90) 0.06 mg/L) was more active than the macrolides (MIC(90) > or = 2 mg/L) and fluoroquinolones (MIC(90) > or = 0.5 mg/L) against penicillin-resistant Streptococcus pneumoniae. The fluoroquinolones were the most active agents tested against beta-lactamase-positive Haemophilus influenzae (MIC(90) < or = 0.01-0.06 mg/L), against which ABT-773 (MIC(90) 4 mg/L) was comparable to azithromycin and two- and four-fold more active than erythromycin and clarithromycin, respectively. Against beta-lactamase positive Moraxella catarrhalis, the activity of ABT-773 (MIC(90) 0.06 mg/L) was comparable to gemifloxacin, trovafloxacin, levofloxacin, and ciprofloxacin (MIC(90) 0.03-0.06 mg/L) and 4- to eightfold greater than that of clarithromycin, gatifloxacin, and erythromycin. These data suggest ABT-773 could be a valuable compound for the treatment of respiratory tract infections, including those resistant to usual oral therapy.

In vitro study of the post-antibiotic effect and the bactericidal activity of Cefditoren and ten other oral antimicrobial agents against upper and lower respiratory tract pathogens.

The in vitro post-antibiotic effect (PAE) and batericidal activity of cefditoren was compared to that of cefixime, cefuroxime, loracarbef, cefaclor, amoxicillin, amoxicillin/clavulanate, clarithromycin, azithromycin, erythromycin, and ciprofloxacin against ATCC culture strains and clinical respiratory isolates. A PAE > 1 h was observed for cefditoren and generally for the macrolides against Streptococcus pneumoniae, beta-lactamase-negative Moraxella catarrhalis, and Streptococcus pyogenes, whereas the other beta-lactams showed mixed results. Cefditoren was the only beta-lactam showing significant bactericidal activity (>3 log reduction of viable cells) within 4 h against penicillin-resistant S. pneumoniae. Only cefditoren and ciprofloxacin showed significant bactericidal activity against beta-lactamase-negative (after 24 h) and beta-lactamase-positive strains of H. influenzae (after 12 h). Against beta-lactamase-positive strains of M. catarrhalis, cefditoren was the only agent to show significant bactericidal activity at 6 h (versus cefuroxime and ciprofloxacin at 12 h).

Comparative in vitro activity and post-antibiotic effect of gemifloxacin against Legionella spp.

The comparative in vitro potency and post-antibiotic effect (PAE) of gemifloxacin (SB-265805), moxifloxacin, trovafloxacin, grepafloxacin, levofloxacin, ofloxacin, ciprofloxacin, azithromycin, clarithromycin, erythromycin and rifampicin were evaluated against Legionella pneumophila serogroups 1-9 and 12 (n = 204) and other Legionella spp. (n = 34). MICs were determined by standard two-fold agar dilution. PAE was determined by exposing the isolates to the test agents at 4 x MIC for 1 h. Trovafloxacin was the most potent agent overall (MIC range < or =0.004-0.016 mg/L, MIC(90) < or =0.008 mg/L). Of the other quinolones tested, gemifloxacin, moxifloxacin, grepafloxacin and levofloxacin were more potent (MIC(90) 0.016 mg/L) against L. pneumophila than ciprofloxacin and ofloxacin (MIC(90) 0. 03 mg/L). Against Legionella spp., the test quinolones were more potent (MIC range < or =0.004-0.06 mg/L) than either erythromycin or azithromycin (MIC(90) 0.5 and 0.25 mg/L, respectively). Gemifloxacin had the longest PAE (4.65 h) of the agents tested against erythromycin-resistant L. pneumophila. Of the quinolones, only gemifloxacin, grepafloxacin, levofloxacin and ofloxacin had PAEs of >3 h against erythromycin-resistant Legionella spp. Azithromycin, erythromycin and clarithromycin had PAEs of <3 h against all erythromycin-resistant strains. Against erythromycin-susceptible L. pneumophila, only gemifloxacin, moxifloxacin, ofloxacin and ciprofloxacin had PAEs of >3 h, and only rifampicin, ofloxacin, gemifloxacin and erythromycin had PAEs of >2 h against erythromycin-susceptible Legionella spp. The superior potency of gemifloxacin compared with erythromycin indicates that it may be of use in the treatment of legionellosis. The significant PAE described here, combined with favourable pharmacokinetics, supports once-daily dosing for gemifloxacin in the treatment of legionella infections.

In vitro activity of gatifloxacin, compared with ciprofloxacin, clarithromycin, erythromycin, and rifampin, against Legionella species.

Gatifloxacin, a new advanced-generation, 8-methoxy fluoroquinolone, has shown efficacy against a broad spectrum of microorganisms. In this study, the in vitro activity of gatifloxacin was compared with that of ciprofloxacin, clarithromycin, erythromycin, and rifampin against 214 Legionella spp. Species tested in order of frequency were: L. pneumophila serogroups 1 to 9 (181 strains); L. dumoffii (10 strains); L. micdadei (9 strains); L. longbeachae (7 strains); and other Legionella spp. (7 strains). MICs were determined by a standard dilution procedure using buffered yeast extract agar. Gatifloxacin and rifampin were the most active agents against all strains of Legionella tested. Moreover, against L. pneumophila strains tested, gatifloxacin was found to be more active (highest MIC90 = 0.03 mg/L) than ciprofloxacin (highest MIC90 = 0.06 mg/L) and clarithromycin (highest MIC90 = 0.12 mg/L). L. pneumophila serogroups 1 to 4 and 6 to 9 (MIC90 = 0.016 mg/L) were more susceptible to gatifloxacinthan L. pneumophila serogroup 5 (MIC90 = 0.03 mg/L). The activity of gatifloxacin against L. micdadei was equal to that of ciprofloxacin (MIC90 = 0.016 mg/L) and greater than that of erythromycin (MIC90 = 1.0 mg/L). The activity of gatifloxacin against L. dumoffii and L. longbeachae was equal to that of ciprofloxacin (MIC90 = 0.03 mg/L). The activity of gatifloxacin was similar against isolates obtained from both patients and environmental sources.

Age-related differences in pictorial implicit memory: role of perceptual and conceptual processes.

This study examined the effects of perceptual and conceptual encoding processes on younger and older adults' implicit and explicit memory for pictures. During acquisition, participants studied simple line drawings under varying encoding task conditions. Half of the participants judged the orientation of the central object, a perceptual encoding task. The other half indicated the taxonomic category to which the object belonged, a conceptual encoding task. Implicit memory measures were priming in picture-fragment and word-fragment completion. Explicit measures were free recall and recognition. Results showed that the magnitude of age differences in primed picture completion varied across encoding task conditions. Age deficits occurred on both explicit tasks. Implications of these results for current views on implicit memory aging are discussed.

[The existential meaning of time for the aged]. / La signification existentielle du temps chez l'être âgé.

The notion of time is particularly important to seniors. Because their future prospects are more limited, the past plays a very significant role. It serves as an anchor for the present and a guideline for the future. The passage of time is not uniform for everyone. It evolves over years and is based on accumulated experiences and personal factors such as age, activity and interests. For this reason, the older a person gets, the more each minute counts. Time is also indicative of change and is revered as the value of values. It is a useful tool for highlighting and valuing the present moment and the actual task to be accomplished in the here and now. It is essential that nurses understand the subjective reality of time to each individual patient if they are to give quality care. Comprehending time's existential meaning to seniors will add a further dimension to nursing interventions that are based on Watson's model of care.

Comparison of spiramycin and doxycycline for treatment of Chlamydia trachomatis genital infections.

We performed a single blind controlled multicenter study in which we compared the efficacy and safety of 100 mg of doxycycline versus those of 1 g (3 x 10(6) IU) of spiramycin given orally twice daily for 14 days in the treatment of culture-positive Chlamydia trachomatis genitourinary tract infections. A total of 367 patients were enrolled in the study, and 364 patients were evaluable for safety and 265 patients were evaluable for efficacy. The cure rate between treatment groups was not statistically significant, being 98% (125 of 128 patients) in the spiramycin group and 100% (133 of 133 patients) in the doxycycline group. Female patients who received spiramycin were more likely to report dysethesias that resolved after the completion of therapy. The results of the study show that spiramycin is an effective drug for the treatment of C. trachomatis infection and warrants further assessment over a shorter treatment period (7 days) and during pregnancy.