Associative Stimulation of the Supraorbital Nerve Fails to Induce Timing-Specific Plasticity in the Human Blink Reflex

BACKGROUND: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006). METHODOLOGY/PRINCIPAL FINDINGS: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment. CONCLUSION/SIGNIFICANCE: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex

Rates of At-risk Drinking among Patients Presenting to the Emergency Department with Occupational and Nonoccupational Injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71604/1/S1069-6563_03_00538-4.pd

Intact Organization of Tactile Space Perception in Isolated Focal Dystonia

Background: Systematic perceptual distortions of tactile space have been documented in healthy adults. In isolated focal dystonia impaired spatial somatosensory processing is suggested to be a central pathophysiological finding, but the structure of tactile space for different body parts has not been previously explored. Objectives: The objective of this study was to assess tactile space organization with a novel behavioral paradigm of tactile distance perception in patients with isolated focal dystonia and controls. Methods: Three groups of isolated focal dystonia patients (cervical dystonia, blepharospasm/Meige syndrome, focal hand dystonia) and controls estimated perceived distances between 2 touches across 8 orientations on the back of both hands and the forehead. Results: Stimulus size judgments differed significantly across orientations in all groups replicating distortions of tactile space known for healthy individuals. There were no differences between groups in the behavioral parameters we assessed on the hands and forehead. Conclusions: Tactile space organization is comparable between patients with isolated focal dystonia and healthy controls in dystonic and unaffected body parts

Breast tumor characteristics of BRCA1 and BRCA2 gene mutation carriers on MRI

The appearance of malignant lesions in BRCA1 and BRCA2 mutation carriers (BRCA-MCs) on mammography and magnetic resonance imaging (MRI) was evaluated. Thus, 29 BRCA-MCs with breast cancer were retrospectively evaluated and the results compared with an age, tumor size and tumor type matched control group of 29 sporadic breast cancer cases. Detection rates on both modalities were evaluated. Tumors were analyzed on morphology, density (mammography), enhancement pattern and kinetics (MRI). Overall detection was significantly better with MRI than with mammography (55/58 vs 44/57, P = 0.021). On mammography, lesions in the BRCA-MC group were significantly more described as rounded (12//19 vs 3/13, P = 0.036) and with sharp margins (9/19 vs 1/13, P = 0.024). On MRI lesions in the BRCA-MC group were significantly more described as rounded (16/27 vs 7/28, P = 0.010), with sharp margins (20/27 vs 7/28, P < 0.001) and with rim enhancement (7/27 vs 1/28, P = 0.025). No significant difference was found for enhancement kinetics (P = 0.667). Malignant lesions in BRCA-MC frequently have morphological characteristics commonly seen in benign lesions, like a rounded shape or sharp margins. This applies for both mammography and MRI. However the possibility of MRI to evaluate the enhancement pattern and kinetics enables the detection of characteristics suggestive for a malignancy

Gender differences in coerced patients with schizophrenia

European Commission (Quality of life and Management of Living Resources Programme, contract number QLG4-CT- 2002-01036), Czech Ministry of Education research grant MSM002160849, and research grants PRVOUK–P26/LF1/4 and PRVOUK–P03/LF1/

Differential expression of anterior gradient gene AGR2 in prostate cancer

<p>Abstract</p> <p>Background</p> <p>The protein AGR2 is a putative member of the protein disulfide isomerase family and was first identified as a homolog of the <it>Xenopus laevis </it>gene XAG-2. AGR2 has been implicated in a number of human cancers. In particular, AGR2 has previously been found to be one of several genes that encode secreted proteins showing increased expression in prostate cancer cells compared to normal prostatic epithelium.</p> <p>Methods</p> <p>Gene expression levels of AGR2 were examined in prostate cancer cells by microarray analysis. We further examined the relationship of AGR2 protein expression to histopathology and prostate cancer outcome on a population basis using tissue microarray technology.</p> <p>Results</p> <p>At the RNA and protein level, there was an increase in AGR2 expression in adenocarcinoma of the prostate compared to morphologically normal prostatic glandular epithelium. Using a tissue microarray, this enhanced AGR2 expression was seen as early as premalignant PIN lesions. Interestingly, within adenocarcinoma samples, there was a slight trend toward lower levels of AGR2 with increasing Gleason score. Consistent with this, relatively lower levels of AGR2 were highly predictive of disease recurrence in patients who had originally presented with high-stage primary prostate cancer (P = 0.009).</p> <p>Conclusions</p> <p>We have shown for the first time that despite an increase in AGR2 expression in prostate cancer compared to non-malignant cells, relatively lower levels of AGR2 are highly predictive of disease recurrence following radical prostatectomy.</p

Coherent J/psi photoproduction in ultra-peripheral PbPb collisions at root s(NN)=2.76 TeV with the CMS experiment

Peer reviewe

Review article: A European perspective on wind and storm damage – from the meteorological background to index-based approaches to assess impacts

Wind and windstorms cause severe damage to natural and human-made environments. Thus, wind-related risk assessment is vital for the preparation and mitigation of calamities. However, the cascade of events leading to damage depends on many factors that are environment-specific and the available methods to address wind-related damage often require sophisticated analysis and specialization. Fortunately, simple indices and thresholds are as effective as complex mechanistic models for many applications. Nonetheless, the multitude of indices and thresholds available requires a careful selection process according to the target sector. Here, we first provide a basic background on wind and storm formation and characteristics, followed by a comprehensive collection of both indices and thresholds that can be used to predict the occurrence and magnitude of wind and storm damage. We focused on five key sectors: forests, urban areas, transport, agriculture and wind-based energy production. For each sector we described indices and thresholds relating to physical properties such as topography and land cover but also to economic aspects (e.g. disruptions in transportation or energy production). In the face of increased climatic variability, the promotion of more effective analysis of wind and storm damage could reduce the impact on society and the environment.</p

Cross section measurement of t-channel single top quark production in pp collisions at root s=13 TeV

Peer reviewe