Tn1546 is part of a larger plasmid-encoded genetic unit horizontally disseminated among clonal Enterococcus faecium lineages.

OBJECTIVES: To determine the genetic composition of the first VanA-type plasmid (pIP816) reported, which was isolated from a clinical Enterococcus faecium (BM4147) strain in France in 1986, and to reveal the genetic units responsible for the dissemination of the vanA gene cluster by comparisons with current, published and additionally generated vanA-spanning plasmid sequences obtained from a heterogeneous E. faecium strain collection (n = 28). METHODS: Plasmid sequences were produced by shotgun sequencing using ABI dye chemistry and primer walking, and were subsequently annotated. Comparative sequence analysis of the vanA region was done with published plasmids, with a partial vanA plasmid (pVEF4) reported here and to >140 kb of sequence obtained from a collection of vanA-harbouring plasmid fragments. RESULTS: Bioinformatic analyses revealed that pIP816 from 1986 and contemporary vanA plasmids shared a conserved genetic fragment of 25 kb, spanning the 10.85 kb vanA cluster encoded by Tn1546, and that the larger unit is present in both clinical and animal complexes of E. faecium. A new group II intron in pVEF4 was characterized. CONCLUSIONS: Comparative DNA analyses suggest that Tn1546 disseminates in and between clonal complexes of E. faecium as part of a larger genetic unit, possibly as a composite transposon flanked by IS1216 elements.

Occurrence of cognitive symptoms in dental assistants with previous occupational exposure to metallic mercury.

Previous investigations have presented evidence for an increased prevalence of late cognitive effects in dental personnel exposed to metallic mercury. We wanted to examine if there was a correlation between mercury exposure and cognitive effects in a Norwegian population of dental workers, and if so, to quantify the occurrence. The study group consisted of 608 female dental assistants from central Norway and 425 female controls from the general population, all under the age of 70. They had responded to a standardized postal questionnaire (Euroquest) inquiring about seven symptoms in regard to neurology, psychosomatics, memory, concentration, mood, sleep disturbances, and fatigue. A score was calculated for each symptom based on 4-15 single questions graded on a scale from 1 (seldom or never) to 4 (very often). Dental assistants and controls had a participation rate of 56.4% and 42.9% respectively. Dental assistants reported more cognitive symptoms than the controls, but on average they reported having each of the symptoms "now and then" or less frequently. There were 4.4% of the dental assistants and 2.8% of the controls who reported having three or more of the seven symptoms "often" or more frequently. The corresponding figures for five or more of the seven symptoms were 1.0% and 0.5% respectively. The occurrence of cognitive malfunction may be moderately increased in dental assistants. For dental assistants there was a relative risk of 1.6 of having three or more symptoms "often" or more frequently, and a relative risk of 2.0 of having five or more symptoms as frequently. It can be assumed from our results that the prevalence of possibly work-related cognitive malfunction in dental assistants is between 0.4% and 2.8%, dependent on the applied severity.

Complete sequence of Enterococcus faecium pVEF3 and the detection of an omega-epsilon-zeta toxin-antitoxin module and an ABC transporter.

Glycopeptide resistant Enterococcus faecium (GREF) persists on Norwegian poultry farms despite the ban on the growth promoter avoparcin. The biological basis for long-term persistence of avoparcin resistance is not fully understood. This study presents the complete DNA sequence of the E. faecium R-plasmid pVEF3 and functional studies of some plasmid-encoded traits (a toxin-antitoxin (TA) system and an ABC transporter) that may be of importance for plasmid persistence. The pVEF3 (63.1 kbp), isolated from an E. faecium strain of poultry origin sampled in Norway in 1999, has 71 coding sequences including the vanA avoparcin/vancomycin resistance encoding gene cluster. pVEF3 encodes the TA system omega-epsilon-zeta, and plasmid stability tests and transcription analysis show that omega-epsilon-zeta is functional in Enterococcus faecalis OGIX, although with decreasing effect over time. The predicted ABC transporter was not found to confer reduced susceptibility to any of the 28 substances tested. The TA system identified in the pVEF-type plasmids may contribute to vanA plasmid persistence on Norwegian poultry farms. However, size and compositional heterogeneity among E. faecium vanA plasmids suggest that additional plasmid maintenance systems in combination with host specific factors and frequent horizontal gene transfer and rearrangement causes the observed plasmid composition and distribution patterns.

Comparative DNA analysis of two vanA plasmids from Enterococcus faecium strains isolated from poultry and a poultry farmer in Norway.

The DNA sequences of two plasmids carrying vanA, pVEF1 (39,626 bp) and pVEF2 (39,714 bp), were determined. Forty-three shared coding sequences were identified, and the only nucleotide difference was an 88-bp indel. A postsegregational killing system was identified. This system possibly explains the persistence of the vanA gene cluster in Norwegian poultry farms.

Persistence of animal and human glycopeptide-resistant enterococci on two Norwegian poultry farms formerly exposed to avoparcin is associated with a widespread plasmid-mediated vanA element within a polyclonal enterococcus faecium population.

The evolutionary processes responsible for the long-term persistence of glycopeptide-resistant Enterococcus faecium (GREF) in nonselective environments were addressed by genetic analyses of E. faecium populations in animals and humans on two Norwegian poultry farms that were previously exposed to avoparcin. A total of 222 fecal GREF (n = 136) and glycopeptide-susceptible (n = 86) E. faecium (GSEF) isolates were obtained from farmers and poultry on three separate occasions in 1998 and 1999. Pulsed-field gel electrophoresis (PFGE) and plasmid DNA analyses discerned 22 GREF and 32 GSEF PFGE types within shifting polyclonal animal and human E. faecium populations and indicated the presence of transferable plasmid-mediated vanA resistance, respectively. Examples of dominant, persistent GREF PFGE types supported the notion that environmentally well-adapted GREF types may counteract the reversal of resistance. PFGE analyses, sequencing of the purK housekeeping gene, and partial typing of vanA-containing Tn1546 suggested a common animal and human reservoir of glycopeptide resistance. Inverse PCR amplification and sequence analyses targeting the right end of the Tn1546-plasmid junction fragment strongly indicated the presence of a common single Tn1546-plasmid-mediated element in 20 of 22 GREF PFGE types. This observation was further strengthened by vanY-vanZ hybridization analyses of plasmid DNAs as well as the finding of a physical linkage between Tn1546 and a putative postsegregation killing system for seven GREF PFGE types. In conclusion, our observations suggest that the molecular unit of persistence of glycopeptide resistance is a common mobile plasmid-mediated vanA-containing element within a polyclonal GREF population that changes over time. In addition, we propose that "plasmid addiction systems" may contribute to the persistence of GREF in nonselective environments.

Neuropsychological function in nonpsychotic unipolar major depression.

OBJECTIVE: To examine neuropsychological deficits in unmedicated patients with a nonpsychotic unipolar major depressive disorder. BACKGROUND: Although cognitive deficits in depression have been reported in several studies, most previous studies have concentrated on a few areas of cognition in more or less heterogenous groups of depressives. METHOD: Twenty-two nonhospitalized patients with a DSM-III-R defined nonpsychotic unipolar major depressive disorder were compared with 30 healthy controls. Neuropsychological tests were organized in the following functions: motor function, selective attention, mental flexibility, visuomotor tracking, working memory, short-term memory, verbal long-term memory, nonverbal long-term memory, verbal fluency, and visuospatial function. RESULTS: There emerged an overall group difference in neuropsychological test performance, with patients scoring significantly lower than controls. Bonferroni corrected univariate analyses of variance showed that patients performed significantly below controls in the following areas: selective attention, working memory, verbal long-term memory, and verbal fluency. Two functions were areas of differential deficits in the depressed group: selective attention and working memory. Impaired verbal long-term memory seemed to reflect an underlying working memory deficit. CONCLUSIONS: Nonhospitalized patients with a nonpsychotic unipolar major depressive disorder exhibited an overall neuropsychological deficit and they performed disproportionately worse in the two domains of selective attention and working memory. The neurobiological implications of the present results are in accordance with the hypothesis that there is a global-diffuse impairment of brain function with particular involvement of the frontal lobes in nonpsychotic unipolar major depressive disorder.

Memory functioning and emotional changes in early phase multiple sclerosis.

Memory functioning and emotional changes were evaluated in 26 early phase multiple sclerosis (MS) patients, as compared with 24 healthy controls. There were no significant differences between the groups with respect to age, education, verbal intelligence, or general visual information processing abilities. The MS group performed significantly below controls on the recognition of nonsense visual stimuli. On most verbal memory test indicators, the MS group did not perform deficiently, but there emerged a between-group difference at trend level on a measure reflecting sensitivity to proactive inhibition. The MS patients reported emotional changes and increased levels of psychological symptoms in several areas. Memory task performance was not significantly correlated with subjective complaints of memory impairment, depressive symptoms, or degree of physical disability. However, subjective complaints of memory impairment were related to depression.

Memory functioning in patients with primary fibromyalgia and major depression and healthy controls.

Memory functioning was assessed in 25 primary fibromyalgia (FM) patients by comparing them with 22 major depressed patients and 18 healthy controls. A broad range of short- and long-term memory tasks were included. Both major depressed and FM patients were significantly impaired on long-term memory tasks requiring effortful processing, compared to healthy controls. When the depressive status of the fibromyalgia patients was accounted for, only the subsample with a lifetime major depressive disorder showed memory impairment as compared with the healthy controls.

Information processing in primary fibromyalgia, major depression and healthy controls.

OBJECTIVE: To assess the information processing capabilities in 25 patients with primary fibromyalgia (FM) by comparing them with 22 patients with major depression and 18 healthy controls. METHODS: A broad range of tasks related to various subcomponents of information processing were included. RESULTS: Our results indicated that patients with primary FM in general share with depressives a nonspecific deficit in information processing capacity. However, our data showed that cognitive dysfunction reflecting a presumed compromise of the right hemisphere is present in major depression, but not in primary FM. CONCLUSION: This finding would suggest that primary FM and depression are probably different conditions.

The effect of specific hypnotic suggestions on blood pressure in normotensive subjects.

Twenty normotensive subjects participated on a voluntary basis in an experiment designed to study the effects of specific suggestions on blood pressure (BP). After an induction procedure, the experimental group received suggestions presumed to be relatively nonactivating, although capable of lowering or raising BP. A control group was used to record the BP changes over time. All subjects met for one session. Eight subjects from the experimental group met for a second session. Both adaptation and induction resulted in significant BP decreases. A specific suggestion to increase BP gave a significant result when compared to the induction point. There was no significant change from induction to the BP decrease suggestion. Both systolic and diastolic BP behaved in the same way. A second experimental session resulted in no significant change compared with the first session. Also, no significant difference was found in suggestibility scores from the first to the second session. The results are in line with previously published studies.

Blood pressure responses to hypnotic and nonhypnotic suggestions in normotensive subjects.

Forty normotensive subjects participated on a voluntary basis in a study designed to compare the effect of suggestions on blood pressure (BP). Two experimental groups received suggestions presumed to be specific in lowering or raising BP after simple relaxation (relaxation group) or hypnotic induction (hypnotic group). A control group was used to record the BP changes over time. The time variable was significant for both systolic (SBP) and diastolic blood pressure (DBP). Induction procedures (hypnosis or relaxation) resulted in significant decreases in DBP in both experimental groups. In the control group there was a significant decrease in SBP. A specific suggestion to increase the BP resulted only in DBP increase in the hypnotic group. This group also gave an increase of both SBP and DBP over the entire experiment, whereas the relaxation group resulted in a significant decrease in SBP. There was no significant group variable, indicating no differences between the groups. Further research is needed to enable firm conclusions of the effect of suggestions on BP.