Diffusion tensor and magnetization transfer MRI measurements of periventricular white matter hyperintensities in old age

Regions of diffuse periventricular white matter hyperintensities (PVWMH) are a common finding on T(2)-weighted MRI scans of older subjects, but their aetiology remains unclear. The aim of this study was to characterize differences in water diffusion and magnetization transfer MRI parameters between macroscopically normal-appearing white matter (NAWM) and PVWMH in a cohort of normal older subjects. Forty-two non-demented 83-year olds underwent structural, diffusion tensor and magnetization transfer MRI. Mean diffusivity (), fractional anisotropy (FA), axial (lambda(ax)) and radial (lambda(rad)) diffusivity, and magnetization transfer ratio (MTR) were measured in both NAWM and PVWMH in frontal and parieto-occipital white matter, and centrum semiovale. For all three regions, PVWMH had greater , lambda(ax) and lambda(rad) than NAWM, while FA and MTR were significantly reduced compared with normal tissue (p<0.01). For PVWMH, MTR was significantly correlated (Spearman's rho in the range -0.93 to 0.70; p<0.01) with , FA, lambda(ax) and lambda(rad) in all three regions. Conversely, for NAWM, the only significant correlation between MTR and a water diffusion parameter was for lambda(rad) in parieto-occipital white matter (rho=-0.40; p<0.05), with all other correlations close to the rho=0 level. These data indicate that in normal white matter, characterized by structurally coherent cell membranes, the degree of water molecule diffusion and myelination are held within relatively tight limits. However, within PVWMH, MTR correlates strongly with water diffusion parameters probably because of the pathologically associated neuronal loss, demyelination and gliosis.     

The effect of the vaccinia K1 protein on the PKR-eIF2α pathway in RK13 and HeLa cells

Activated PKR protein regulates downstream anti-viral effects, including inhibition of translation. Thus, many viruses encode proteins to inhibit PKR. Here, we provide evidence that the vaccinia virus K1 protein, a host-range protein, possesses this function. First, the expression of the wild-type K1 protein was necessary to inhibit virus-induced eIF2α phosphorylation, an indirect measure of PKR activation, in RK13 and HeLa cells. Second, virus-induced eIF2α phosphorylation no longer occurred in PKR-deficient HeLa cells, suggesting PKR was responsible for vaccinia virus-induced eIF2α modification. Third, in normal HeLa cells, K1 protein expression also prevented virus-mediated PKR phosphorylation (activation). Residues in the C-terminal portion of the ANK2 region of K1 were identified as necessary for this inhibitory phenotype. Interestingly, mutant viruses that failed to inhibit PKR activation, such as S2C#2, also did not replicate in HeLa cells, suggesting that K1's inhibition of PKR was required for a productive infection. In support of this theory, when PKR was absent from HeLa cells, there was a modest restoration of viral protein synthesis during S2C#2 infection. However, the increased protein synthesis was insufficient for a productive infection.     

Cross-Sectional and Longitudinal Multilocus Sequence Typing of Pseudomonas aeruginosa in Cystic Fibrosis Sputum Samples

Multilocus sequence typing (MLST) is a genetic typing tool designed to provide information about the relatedness of isolates at the core genome level. The utility of MLST in regard to cystic fibrosis (CF)-related infection with Pseudomonas aeruginosa is unknown. The molecular clock speed of the MLST genes was studied using 219 colonies isolated longitudinally from 49 patients with CF. A cross-sectional study examining 27 to 46 colonies per sputum sample for samples from 16 patients was also undertaken. The molecular clock speed was estimated to be 2.05 × 10⁻⁵ (upper 95% confidence limit) or 4.75 × 10⁻⁶ (50% confidence limit) point mutations per nucleotide per year. In the cross-sectional study, 50% of patients were infected with more than one sequence type. There was evidence of point mutations, recombination events, and coinfection with epidemic and unique strains. A clonal complex that was highly genetically distinct from the rest of the P. aeruginosa population was identified. The MLST scheme uses genes with an appropriate clock speed and provides useful information about the genetic variation of P. aeruginosa within and between patients with CF.Multilocus sequence typing (MLST) is a typing tool based on the DNA sequences of several housekeeping genes. Housekeeping genes are chosen because they are assumed to be under low selection pressure and therefore to have a low molecular clock speed, i.e., to undergo mutations at a low rate. This allows MLST to provide data about the core evolutionary genome of a bacterium which allow deductions about population structure and the relatedness of different strains. Where populations are rapidly diversifying by recombination, as may occur in a clinical outbreak, MLST is able to identify closely related isolates (22) which may have undergone changes in one or two loci. MLST has recently been used to estimate the molecular clock speed of the housekeeping genes in cystic fibrosis (CF)-related Burkholderia cepacia complex infection and to identify presumed recombination events in infected patients (24). We hypothesized that the clock speed of the housekeeping genes of the Pseudomonas aeruginosa MLST scheme in patients with CF would be of the same order and that point mutations and recombination events would be identified. These hypotheses were tested by examining sequential isolates from chronically infected patients with CF (clock speed study) and by examining multiple isolates from single sputum samples (cross-sectional study).     

Left-hand somatosensory stimulation combined with visual scanning training in rehabilitation for post-stroke hemineglect: a randomised, double-blind study

The aim of this randomised, double-blind study was to investigate the therapeutic effectiveness of left-hand electrical stimulation for patients with post-stroke left visuo-spatial neglect. This approach was hypothesised to enhance activation of the right hemisphere attention system and to improve visual exploration of extrapersonal space. Participants (n = 40) in the study were in a relatively early stage of recovery from their first right hemisphere stroke, and were randomly assigned to the experimental (E) or control (C) group. Group E received conventional visual scanning training combined with electrostimulation of the left hand, while Group C received scanning training with sham stimulation. Their visuo-spatial neglect was assessed twice, prior to the rehabilitation programme and on its completion, using cancellation tests and a letter-reading task. The effect of electrostimulation on hemineglect was assessed following a single administration and after a month-long rehabilitation programme. Although the immediate effect of stimulation was poor, after a month-long rehabilitation period we found significantly greater improvement in Group E patients than in Group C patients. Interestingly, the presence of hemisensory loss did not weaken the observed effect. Therefore, we claim that contralesional hand stimulation combined with visual scanning was a more effective treatment for hemineglect rehabilitation than scanning training alone.     

Personality and the bipolar spectrum: normative and classification data for the Eysenck Personality Questionnaire-Revised

Background

Personality traits dispose individuals toward particular affective states and may therefore have an important role in the etiology of affective disorders in particular. Despite being one of the most widely used and well-researched personality instruments, few studies have studied bipolar spectrum disorders using the revised Eysenck Personality Questionnaire (EPQ-R) (Eysenck HJ, Eysenck SBG. The Eysenck Personality Questionnaire-Revised. Sevenoaks: UK; Hodder & Stoughton, 1992).

Methods

The EPQ-R was administered to 50 bipolar patients, 50 unipolar patients, and 50 controls matched on age and sex. Participants in clinical groups were euthymic, and participants in the control groups were screened for symptoms of depression.

Results

The EPQ-R scores were most effective at discriminating unipolar patients from controls, such that unipolar patients were higher on neuroticism and lower on extraversion. Bipolar patients showed a similar personality profile to, but were not clearly distinguished from, unipolar patients.

Conclusions

This research provides preliminary normative data for the EPQ-R that complement previous theoretical and empirical work in this area and suggests the usefulness of this tool in a clinical setting.     

The selective estrogen receptor α agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: A phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine

Objective

Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor α (ERα) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity.

Methods

A 10‐week, multicenter, randomized, double‐blind, placebo‐controlled, parallel group, dose‐finding, proof‐of‐concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28).

Results

Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose‐related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial.

Conclusion

The observed lack of clinical benefit in RA patients treated with an ERα agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERα‐mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.

     

Approaches to Breast Cancer Screening Among Primary Care Physicians in Rural Areas of Crete,Greece

The aim of this study was to assess levels of knowledge regarding breast cancer screening among primary care physicians in rural areas of Crete. A cross-sectional survey of 106 general practitioners and internists and 83 trainee general practitioners (GPs) employed as of October 2004 and practicing at 14 primary health centers in Crete was performed. It was a self-administered survey with 27 items exploring knowledge, attitudes, and behaviors concerning delivery of general preventive and cancer screening services. The main outcome measures were responses to four items on approaches to breast cancer screening practices. Overall response rate was 55% (primary care physicians (PCPs) = 53%; trainee GPs = 60%). Respondents demonstrated a limited awareness of international recommendations for breast cancer screening and exhibited marked variation in their responses to survey items. Agreement with current international guidelines ranged from 31% to 58% for the individual survey items. This survey revealed limited knowledge among PCPs to well-publicized breast cancer screening guidelines and variations in approaches to breast cancer early detection.