Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone.

BACKGROUND: New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype. AIM: To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England. METHODS: Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains. FINDINGS: By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 × 10(-6), Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006. CONCLUSIONS: Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms.

Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody.

Upregulation of Toll-like receptor 2 (TLR2) plays a critical role in inflammation associated with ischemia/reperfusion-induced tissue damage. OPN-305 is the first humanized IgG4 monoclonal antibody against TLR2 in development and is intended for the prevention of reperfusion injury following renal transplantation and other indications. A phase I, single-center, prospective randomized, double-blind, placebo-controlled study was performed to evaluate single ascending doses of OPN-305 in 41 healthy male subjects (age range: 19-58 years) randomized to OPN-305 or placebo across six cohorts. OPN-305 was well tolerated across all doses, with no elevations in endogenous cytokines. A dose-proportional increase in maximum serum concentration (Cmax) was observed, with area under the curve increasing in a greater-than-dose-proportional manner with increasing elimination half-life. OPN-305 produced full TLR2 receptor blockade on CD14(+)CD45(+) cells (monocytes), from 14 (0.5 mg/kg) to >90 (10 mg/kg) days, with a linear effect on the duration of inhibition of interleukin-6 release after TLR2 stimulation.

Patterns of diversity and adaptation in Glomeromycota from three prairie grasslands.

Arbuscular mycorrhizal (AM) fungi are widespread root symbionts that often improve the fitness of their plant hosts. We tested whether local adaptation in mycorrhizal symbioses would shape the community structure of these root symbionts in a way that maximizes their symbiotic functioning. We grew a native prairie grass (Andropogon gerardii) with all possible combinations of soils and AM fungal inocula from three different prairies that varied in soil characteristics and disturbance history (two native prairie remnants and one recently restored). We identified the AM fungi colonizing A. gerardii roots using PCR amplification and cloning of the small subunit rRNA gene. We observed 13 operational taxonomic units (OTUs) belonging to six genera in three families. Taxonomic richness was higher in the restored than the native prairies with one member of the Gigaspora dominating the roots of plants grown with inocula from native prairies. Inoculum source and the soil environment influenced the composition of AM fungi that colonized plant roots. Correspondingly, host plants and AM fungi responded significantly to the soil-inoculum combinations such that home fungi often had the highest fitness and provided the greatest benefit to A. gerardii. Similar patterns were observed within the soil-inoculum combinations originating from two native prairies, where five sequence types of a single Gigaspora OTU were virtually the only root colonizers. Our results indicate that indigenous assemblages of AM fungi were adapted to the local soil environment and that this process occurred both at a community scale and at the scale of fungal sequence types within a dominant OTU.

Qualitative effects of fresh and dried plum ingredients on vacuum-packaged, sliced hams.

Boneless ham muscles (Semimembranosus+Adductor) were injected (20% w/w) with a curing brine containing no plum ingredient (control), fresh plum juice concentrate (FP), dried plum juice concentrate (DP), or spray dried plum powder (PP) at 2.5% or 5%. Hams were cooked, vacuum-packaged, stored at<4°C and evaluated at 2-week intervals over 10 week. Evaluations were performed on sliced product to determine cook loss, vacuum-package purge, Allo-Kramer shear force, 2-thiobarbituric acid-reactive substances (TBARS), proximate analysis, objective color, sensory panel color and sensory attributes. FP, DP and 2.5% PP increased (P<0.05) cook loss by 2% to 7% depending on treatment and level, but the highest cook loss (17.7%) was observed in hams with 5% PP. Shear force values increased as the level of plum ingredient increased (P<0.05) from 2.5% to 5%, and the highest shear values were observed in hams containing 5% FP. There were no differences (P>0.05) in lipid oxidation among treatments as determined by TBARS and sensory evaluation. FP and PP ham color was similar to the control, but DP had a more intense atypical color of cured ham. Minimal changes in physical, chemical and sensory properties were observed during storage of all treatments.

Temporal changes in C and N stocks of restored prairie: implications for C sequestration strategies.

The recovery of ecosystem C and N dynamics after disturbance can be a slow process. Chronosequence approaches offer unique opportunities to use space-for-time substitution to quantify the recovery of ecosystem C and N stocks and estimate the potential of restoration practices for C sequestration. We studied the distribution of C and N stocks in two chronosequences that included long-term cultivated lands, 3- to 26-year-old prairie restorations, and remnant prairie on two related soil series. Results from the two chronosequences did not vary significantly and were combined. Based on modeling predictions, the recovery rates of different ecosystem components varied greatly. Overall, C stocks recovered faster than N stocks, but both C and N stocks recovered more rapidly for aboveground vegetation than for any other ecosystem component. Aboveground C and N reached 95% of remnant levels in only 13 years and 21 years, respectively, after planting to native vegetation. Belowground plant C and N recovered several decades later, while microbial biomass C, soil organic C (SOC), and total soil N recovered on a century timescale. In the cultivated fields, SOC concentrations were depleted within the surface 25 cm, coinciding with the depth of plowing, but cultivation apparently led to redistribution of soil C, increasing SOC stocks deeper in the soil profile. The restoration of prairie vegetation was effective at rebuilding soil organic matter (SOM) in the surface soil. Accrual rates were maintained at 43 g C x m(-2) x yr(-1) and 3 g N x m(-2) x yr(-1) in the surface 0.16 Mg/m2 soil mass during the first 26 years of restoration and were predicted to reach 50% of their storage potential (3500 g C/m2) in the first 100 years. We conclude that restoration of tallgrass prairie vegetation can restore SOM lost through cultivation and has the potential to sequester relatively large amounts of SOC over a sustained period of time. Whether restored prairies can retain the C apparently transferred to the subsoil by cultivation practices remains to be seen.

Isoform-specific effects of ApoE on HSV immediate early gene expression and establishment of latency.

Alzheimer's disease (AD) is a common and devastating neurodegenerative disease in which most cases are of unknown, sporadic origin. In addition to age, the most prevalent known risk factor for developing AD is carriage of the epsilon4 allele of Apolipoprotein E (ApoE). Carriage of the epsilon2 or epsilon3 allele of ApoE confers protection or no change in risk for AD, respectively. Latent herpes simplex virus type 1 (HSV-1) infection in the brain concurrent with ApoE4 carriage exacerbates risk for AD, suggesting that these two factors interact to promote neuronal dysfunction and degeneration in selective brain areas. Indeed, HSV-1 DNA has been found in regions primarily affected by AD, such as the temporal lobes, hippocampus, and neocortex. We hypothesize that HSV-1 infection in the background of ApoE4, but not ApoE2 or ApoE3, promotes an environment more conducive to neuronal degeneration. To investigate this idea, we have utilized transgenic mice that express human ApoE2, 3, or 4 alleles from astrocytes in a murine ApoE -/- background. We find that carriage of the different ApoE alleles dramatically affects HSV-1 immediate early gene expression as well as the establishment of latency. Both of these factors are poised to impact neuronal viability, inflammation, and viral spread. Our data support the concept that HSV-1 and ApoE4 interact to provide an environment conducive to the development and/or spread of AD.

Memories and anticipations control responding by rats (Rattus norvegicus) in a Pavlovian procedure.

In Experiment 1 each rat received two different fixed series of three trials each. The unconditioned stimulus occurred on Trial 1 of one series and on Trial 3 of the other series, all other trials being nonreinforced. Previous Pavlovian investigations have shown that rats can remember the immediately prior reward outcome and anticipate the immediately subsequent reward outcome. Experiment 1 demonstrated that rats could remember and anticipate even more remote reward outcomes. In Experiment 2 two groups received a series of two nonrewarded trials followed by a rewarded trial. It was demonstrated that a change in the conditioned stimulus (CS) from Trial 2 to Trial 3, which occurred in one group, produced weaker responding than in the other group that did not experience such CS change. On the basis of these findings it was suggested that the rats organized the trials of a series into a unit or chunk. This was concluded for two reasons. First, remembering and anticipating remote reward outcomes strongly suggests that responding is being controlled by events extending beyond the current trial. Secondly, the experimental manipulations employed in the Pavlovian situation here are similar to those used in prior human learning and animal instrumental learning investigations concerned with chunking. Thus, it would appear that chunking is a ubiquitous phenomenon appearing in human serial learning (e.g., Bower and Winzenz 1969; Crowder 1976), in animal instrumental learning (e.g., Capaldi 1992; Hulse and Dorsky 1977; Terrace 1987), and now in Pavlovian learning.

CCS/CAR/CANM/CNCS/CanSCMR joint position statement on advanced noninvasive cardiac imaging using positron emission tomography, magnetic resonance imaging and multidetector computed tomographic angiography in the diagnosis and evaluation of ischemic heart disease--executive summary.

BACKGROUND: Over the past few decades, advanced imaging modalities with excellent diagnostic capabilities have emerged. The aim of the present position statement was to systematically review existing literature to define Canadian recommendations for their clinical use. METHODS: A systematic literature review to 2005 was conducted for positron emission tomography (PET), multidetector computed tomographic angiography and magnetic resonance imaging (MRI) in ischemic heart disease. Papers that met the criteria were reviewed for accuracy, prognosis data and study quality. Recommendations were presented to primary and secondary panels of experts, and consensus was achieved. RESULTS: Indications for PET include detection of coronary artery disease (CAD) with perfusion imaging, and defining viability using fluorodeoxyglucose to determine left ventricular function recovery and/or prognosis after revascularization (class I). Detection of CAD in patients, vessel segments and grafts using computed tomographic angiography was considered class IIa at the time of the literature review. Dobutamine MRI is class I for CAD detection and, along with late gadolinium enhancement MRI, class I for viability detection to predict left ventricular function recovery. Imaging must be performed at institutions and interpreted by physicians with adequate experience and training. CONCLUSIONS: Cardiac imaging using advanced modalities (PET, multidetector computed tomographic angiography and MRI) is useful for CAD detection, viability definition and, in some cases, prognosis. These modalities complement the more widespread single photon emission computed tomography and echocardiography. Given the rapid evolution of technology, initial guidelines for clinical use will require regular updates. Evaluation of their integration in clinical practice should be ongoing; optimal use will require proper training. A joint effort among specialties is recommended to achieve these goals.

Temporal evolution of mouse striatal gene expression following MPTP injury.

The gradual loss of striatal dopamine and dopaminergic neurons residing in the substantia nigra (SN) causes parkinsonism characterized by slow, halting movements, rigidity, and resting tremor when neuronal loss exceeds a threshold of approximately 80%. It is estimated that there is extensive compensation for several years prior to symptom onset, during which vulnerable neurons asynchronously die. Recent evidence would argue that much of the compensatory response of the nigrostriatal system is multimodal including both pre-synaptic and striatal mechanisms. Although parkinsonism may have multiple causes, the classic syndrome, Parkinson's disease (PD), is frequently modeled in small animals by repeated administration of the selective neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Because the MPTP model of PD recapitulates many of the known behavioral and pathological features of human PD, we asked whether the striatal cells of mice treated with MPTP in a semi-chronic paradigm enact a transcriptional program that would help elucidate the response to dopamine denervation. Our findings reveal a time-dependent dysregulation in the striatum of a set of genes whose products may impact both the viability and ability to communicate of dopamine neurons in the SN.

Mycorrhizal mediated feedbacks influence net carbon gain and nutrient uptake in Andropogon gerardii.

• The carbon sink strength of arbuscular mycorrhizal fungi (AMF) was investigated by comparing the growth dynamics of mycorrhizal and nonmycorrhizal Andropogon gerardii plants over a wide range of equivalent tissue phosphorus : nitrogen (P : N) ratios. • Host growth, apparent photosynthesis (Anet ), net C gain (Cn ) and P and N uptake were evaluated in sequential harvests of mycorrhizal and nonmycorrhizal A. gerardii plants. Response curves were used to assess the effect of assimilate supply on the mycorrhizal symbiosis in relation to the association of C with N and P. • Mycorrhizal plants had higher Cn than nonmycorrhizal plants at equivalent shoot P : N ratios even though colonization did not affect plant dry mass. The higher Cn in mycorrhizal plants was related to both an increase in specific leaf area and enhanced photosynthesis. The additional carbon gain associated with the mycorrhizal condition was not allocated to root biomass. The Cn in the mycorrhizal plants was positively related to the proportion of active colonization in the roots. • The calculated difference between Cn values in mycorrhizal and nonmycorrhizal plants, Cdiff , appeared to correspond to the sink strength of the AMF and was not an indirect result of enhanced nutrition in mycorrhizal plants.

Behavior and misbehavior of the horse.

For decades after the discipline of psychiatry had been established as an accepted specialty, many medical schools continued to fail to train their students in the fundamentals of this discipline. Medical students all have at least cursory exposure to psychiatric principles and basic psychology. Unfortunately, the veterinary profession has lagged behind human medicine in this regard. Until recently, veterinary students received no training in animal behavior, and there were no available residencies within our schools for developing board-certified behavioral specialists.

Coping with metastatic melanoma: the last year of life.

BACKGROUND: Few longitudinal studies have concurrently investigated cognitive appraisal, coping and psychological adjustment in patients with terminal cancer. This study aimed to (i) consider patterns of change in these variables during the last year of life and (ii) consider covariates associated with patients' psychological adjustment. METHODS AND PATIENTS: Questionnaires were sent to a cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between 1991 and 1996, approximately every 3 months, for up to 2 years. A sub-sample of 110 patients completed at least one questionnaire in the last year of life. Repeated measures linear regression was used to model cognitive appraisal, coping and psychological adjustment. RESULTS: In the last year of life, patients' cognitive appraisal of their disease remained relatively stable, whereas their use of active coping strategies increased (p=0. 04). There was some deterioration in psychological adjustment, particularly in patients' ability to minimize the impact of cancer on daily life (p=0.03), but this effect did not remain significant when patients' level of tiredness was included in the model. Cognitive appraisal, coping style and quality of life indicators were all associated with psychological adjustment. CONCLUSION: These findings suggest that while patients work hard to actively cope with their disease, they experience increasing levels of tiredness, and deterioration in their mood and ability to function in their daily lives.

Thrombosed giant coronary artery aneurysm presenting as an intracardiac mass.

Giant coronary artery aneurysms are rare in adults and are usually found in association with Kawasaki's disease arising in childhood. We report a case of a thrombosed giant right coronary artery aneurysm presenting as an intracardiac mass detected after inferior wall myocardial infarction. Histologic analysis indicated that fibromuscular dysplasia was the underlying cause of the aneurysm.

Advances in the management of dysphagia caused by stroke.

This article reviews the advancements that have occurred, primarily in the last decade, in the management and treatment of swallowing disorders related to stroke. An overview of swallowing physiology is given, and interventions, both indirect and direct, are explored. Expanding knowledge, applying techniques from other scientific disciplines, and developing new technologies provide hope for stroke patients who experience dysphagia.

Stroke: current concepts of care.

Despite the approval of the use of tissue plasminogen activator for the treatment of acute stroke, less than 10% of all patients with stroke are able to reach a medical facility in time to receive the treatment. This article reviews the current concepts of stroke management and emphasizes the importance of public awareness for the signs and symptoms of stroke and the need for immediate attention when a stroke is suspected.

Mycorrhizal status of the genus Carex (Cyperaceae).

The Cyperaceae have generally been considered nonmycorrhizal, although recent evidence suggests that mycotrophy may be considerably more widespread among sedges than was previously realized. This study surveyed 23 species of Carex occurring in upland and wetland habitats in northeastern Illinois. Mycorrhizal infection by arbuscular fungi was found in the roots of 16 species of Carex and appears to occur in response to many factors, both environmental and phylogenetic. While some species appear to be obligately nonmycorrhizal, edaphic influences may be responsible for infection in others. In five of the seven Carex species that were nonmycorrhizal, a novel root character, the presence of bulbous-based root hairs, was identified. The taxonomically patchy distribution of the distinctive root hair trait suggests that these structures may have evolved several times within the genus. Evidence of multiple independent origins of the root hair trait lends support to the hypothesis that root hairs represent an adaptation to nonmycotrophy. Although taxonomic position does seem to be of importance in determining the mycorrhizal dependence of sedges, the pattern may be a patchwork of both mycorrhizal clades and clades that have adapted to the nonmycorrhizal state.