Sentence context prevails over word association in aphasia patients with spared comprehension : evidence from N400 event-related potential

Behavioral and event-related potential (ERP) studies on aphasia patients showed that lexical information is not lost but rather its integration into the working context is hampered. Studies have been conducted on the processing of sentence-level information (meaningful versus meaningless) and of word-level information (related versus unrelated) in aphasia patients, but we are not aware of any study that assesses the relationship between the two. In healthy subjects the processing of a single word in a sentence context has been studied using the N400 ERP. It was shown that, even when there is only a weak expectation of a final word in a sentence, this expectation will dominate word relatedness. In order to study the effect of semantic relatedness between words in sentence processing in aphasia patients, we conducted a crossed design ERP study, crossing the factors of word relatedness and sentence congruity. We tested aphasia patients with mild to minimum comprehension deficit and healthy young and older (age-matched with our patients) controls on a semantic anomaly judgment task when simultaneously recording EEG. Our results show that our aphasia patient's N400 amplitudes in response to the sentences of our crossed-design study were similar to those of our age-matched healthy subjects. However, we detected an increase in the N400 ERP latency in those patients, indicating a delay in the integration of the new word into the working context. Additionally, we observed a positive correlation between comprehension level of those patients and N400 effect in response to meaningful sentences without word relatedness contrasted to meaningless sentences without word relatedness

Critical illness polyneuropathy and myopathy; a neuromuscular disorder encountered in the intensive care unit

Patients with neuromuscular disorders encountered on the ICU can be divided into two main categories. One category has been admitted to the intensive care unit (ICU) due to an underlying neuromuscular disorder, mainly the Guillam Barre Syndrome ( GBS) and myasthenia gravis. The other category develops a so-called acquired neuromuscular disorder during their stay on the ICU after admission for other reasons (multi-trauma, severe infections, (multiple) organ dysfunction, etcetera). In these patients the neurological symptoms mainly consist of muscle weakness, wasting, and difficulties in weaning from the artificial respirator

Transthyretin levels in the vitreous correlate with change in visual acuity after vitrectomy

Background/aim: Little is known about biochemical markers related to change in visual acuity after vitrectomy. The potential use of transthyretin (TTR), a carrier of the retinol/retinol-binding protein, as a biochemical marker protein, was investigated. Methods: TTR was measured using immunonephelometry in a group of patients (n = 77) in longstanding (> 1 week) retinal detachment (n = 29), fresh (< 1 week) retinal detachment (n = 17), macular holes (n = 20) or diabetic retinopathy (n = 11). Vitreous samples were taken at the start of every vitrectomy procedure. For reference values, cadaver specimens (n = 73) were used. Results: Reference values for vitreous TTR (median 18 mg/l; IQR 4 to 24 mg/l) comprised 2.2% of reference values for vitreous protein levels (median 538 mg/l; IQR 269 to 987 mg/l). Vitreous TTR values of patients were comparable in all disorders. Vitreous TTR values were higher in phakic (median 22.5 mg/l; IQR 10 to 27 mg/l) than in pseudophakic patients (median 12 mg/l; IQR 8 to 19 mg/l; p = 0.06). Postoperative change in visual acuity correlated well with vitreous TTR values found peroperatively (r(s) = 0.408; p = 0.012). Both change in visual acuity and lens status were the only variables which proved to explain the variance of TTR (multiple correlation coefficient: 0.494; phakic status: t = 2.767; p = 0.0084; and change in visual acuity t = 2.924: p = 0.0056). Conclusion: Vitreous fluid concentrations of TTR can be regarded as a biochemical marker for retinal function

Overlapping connectivity patterns during semantic processing of abstract and concrete words revealed with multivariate Granger Causality analysis

Unlike concrete, nouns refer to notions beyond our perception. Even though there is no consensus among linguists as to what exactly constitutes a concrete or abstract word, neuroscientists found clear evidence of a "concreteness" effect. This can, for instance, be seen in patients with language impairments due to brain injury or developmental disorder who are capable of perceiving one category better than another. Even though the results are inconclusive, neuroimaging studies on healthy subjects also provide a spatial and temporal account of differences in the processing of abstract versus concrete words. A description of the neural pathways during abstract word reading, the manner in which the connectivity patterns develop over the different stages of lexical and semantic processing compared to that of concrete word processing are still debated. We conducted a high-density EEG study on 24 healthy young volunteers using an implicit categorization task. From this, we obtained high spatio-temporal resolution data and, by means of source reconstruction, reduced the effect of signal mixing observed on scalp level. A multivariate, time-varying and directional method of analyzing connectivity based on the concept of Granger Causality (Partial Directed Coherence) revealed a dynamic network that transfers information from the right superior occipital lobe along the ventral and dorsal streams towards the anterior temporal and orbitofrontal lobes of both hemispheres. Some regions along these pathways appear to be primarily involved in either receiving or sending information. A clear difference in information transfer of abstract and concrete words was observed during the time window of semantic processing, specifically for information transferred towards the left anterior temporal lobe. Further exploratory analysis confirmed a generally stronger connectivity pattern for processing concrete words. We believe our study could guide future research towards a more refined theory of abstract word processing in the brain

Effects of 3,4-Methylenedioxymethamphetamine Administration on Retinal Physiology in the Rat

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known to produce euphoric states, but may also cause adverse consequences in humans, such as hyperthermia and neurocognitive deficits. Although MDMA consumption has been associated with visual problems, the effects of this recreational drug in retinal physiology have not been addressed hitherto. In this work, we evaluated the effect of a single MDMA administration in the rat electroretinogram (ERG). Wistar rats were administered MDMA (15 mg/kg) or saline and ERGs were recorded before (Baseline ERG), and 3 h, 24 h, and 7 days after treatment. A high temperature (HT) saline-treated control group was also included. Overall, significantly augmented and shorter latency ERG responses were found in MDMA and HT groups 3 h after treatment when compared to Baseline. Twenty-four hours after treatment some of the alterations found at 3 h, mainly characterized by shorter latency, tended to return to Baseline values. However, MDMA-treated animals still presented increased scotopic a-wave and b-wave amplitudes compared to Baseline ERGs, which were independent of temperature elevation though the latter might underlie the acute ERG alterations observed 3 h after MDMA administration. Seven days after MDMA administration recovery from these effects had occurred. The effects seem to stem from specific changes observed at the a-wave level, which indicates that MDMA affects subacutely (at 24 h) retinal physiology at the outer retinal (photoreceptor/bipolar) layers. In conclusion, we have found direct evidence that MDMA causes subacute enhancement of the outer retinal responses (most prominent in the a-wave), though ERG alterations resume within one week. These changes in photoreceptor/bipolar cell physiology may have implications for the understanding of the subacute visual manifestations induced by MDMA in humans

Phase i trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective secondgeneration inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n¼1) in the paclitaxel/carboplatin cohort and fatigue (n¼1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No gradeX3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n¼27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n¼21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug–drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.This study was sponsored by Pfizer Inc. Support was provided in part by National Institutes of Health grant P30 CA006927 to the Fox Chase Cancer Center. We thank the patients who participated in this study and the physicians who referred them, as well as the study coordinators and data managers, Shelley Mayfield and Carol Martins at Pfizer Inc. for support of the study conduct, and Gamal ElSawah, Pfizer Medical Affairs, for his review of the manuscript. Medical writing support was provided by Joanna Bloom, of UBC Scientific Solutions (Southport, CT, USA) and Christine Arris at ACUMED (Tytherington, UK) and was funded by Pfizer In