Temporal Dynamics of Brain White Matter Plasticity in Sighted Subjects during Tactile Braille Learning: A Longitudinal Diffusion Tensor Imaging Study

The white matter (WM) architecture of the human brain changes in response to training, though fine-grained temporal characteristics of training-induced white matter plasticity remain unexplored. We investigated white matter microstructural changes using diffusion tensor imaging at five different time points in 26 sighted female adults during 8 months of training on tactile braille reading. Our results show that training-induced white matter plasticity occurs both within and beyond the trained sensory modality, as reflected by fractional anisotropy (FA) increases in somatosensory and visual cortex, respectively. The observed changes followed distinct time courses, with gradual linear FA increase along the training in the somatosensory cortex and sudden visual cortex cross-modal plasticity occurring after braille input became linguistically meaningful. WM changes observed in these areas returned to baseline after the cessation of learning in line with the supply–demand model of plasticity. These results also indicate that the temporal dynamics of microstructural plasticity in different cortical regions might be modulated by the nature of computational demands. We provide additional evidence that observed FA training-induced changes are behaviorally relevant to tactile reading. Together, these results demonstrate that WM plasticity is a highly dynamic process modulated by the introduction of novel experiences.SIGNIFICANCE STATEMENT Throughout the lifetime the human brain is shaped by various experiences. Training-induced reorganization in white matter (WM) microstructure has been reported, but we know little about its temporal dynamics. To fill this gap, we scanned sighted subjects five times during tactile braille reading training. We observed different dynamics of WM plasticity in the somatosensory and visual cortices implicated in braille reading. The former showed a continuous increase in WM tissue anisotropy along with tactile training, while microstructural changes in the latter were observed only after the participants learned to read braille words. Our results confirm the supply–demand model of brain plasticity and provide evidence that WM reorganization depends on distinct computational demands and functional roles of regions involved in the trained skill.     

Neural response patterns in spider,blood-injection-injury and social fearful individuals: new insights from a simultaneous EEG/ECG–fMRI study

In the present simultaneous EEG/ECG-fMRI study we compared the temporal and spatial characteristics of the brain responses and the cardiac activity during fear picture processing between spider, blood-injection-injury (BII) and social fearful as well as healthy (non-fearful) volunteers. All participants were presented with two neutral and six fear-related blocks of pictures: two social, two spider and two blood/injection fear blocks. In a social fear block neutral images were occasionally interspersed with photographs of angry faces and social exposure scenes. In spider and blood/injection fear blocks neutral pictures were interspersed with spider fear-relevant and blood/injection pictures, respectively. When compared to healthy controls the social fear group responded with increased activations in the anterior orbital, middle/anterior cingulate and middle/superior temporal areas for pictures depicting angry faces and with a few elevated superior frontal activations for social exposure scenes. In the blood/injection fear group, heart rate was decreased and the activity in the middle/inferior frontal and visual processing regions was increased for blood/injection pictures. The HR decrease for blood/injection pictures correlated with increased frontal responses. In the spider fear group, spider fear-relevant pictures triggered increased activations within a broad subcortical and cortical neural fear network. The HR response for spider fear-relevant stimuli was increased and correlated with an increased insula and hippocampus activity. When compared to healthy controls, all fear groups showed higher LPP amplitudes for their feared cues and an overall greater P1 hypervigilance effect. Contrasts against the fear control groups showed that the increased responses for fear-specific stimuli are mostly related to specific fears and not to general anxiety proneness. The results suggest different engagement of cognitive evaluation and down-regulation strategies and an overall increased sensitization of the fear system in the three fear groups.     

Isolation and structural characterization of the photolysis products of etoricoxib

Etoricoxib is a potent and novel selective inhibitor of cyclooxygenase-2 (COX-2) which has been developed for the treatment of osteoarthritis, rheumatoid arthritis and several other inflammatory conditions. To support clinical pharmacokinetics studies, a method for the determination of etoricoxib in human plasma was developed. During the development of the method it was found that highly fluorescent products were formed when etoricoxib was exposed to UV light (254 nm). The formation of highly fluorescent products was the basis for the development of a highly sensitive HPLC/fluorescent assay for the indirect determination of etoricoxib in human plasma; the limit of quantification (LOQ) was 1 ng/mL. To unequivocally determine the chemical structures of the photolysis products of etoricoxib, a series of studies was conducted. When etoricoxib was irradiated online in a photochemical reactor, three products were detected in an HPLC-UV system. These products were characterized by HPLC-UV-fluorescence and HPLC-MS/MS. Possible structures of these products were proposed based on these data. The major photolysis products of etoricoxib were further isolated and their structures were elucidated using NMR and HPLC-NMR. The results of these experiments indicate that etoricoxib undergoes a photocyclization reaction when irradiated with UV light (254 nm), leading to the formation of two major isomeric photocyclization products.     

Determination of simvastatin-derived HMG-CoA reductase inhibitors in biomatrices using an automated enzyme inhibition assay with radioactivity detection

A robust, automated enzyme inhibition assay method was developed and validated for the determination of HMG-CoA reductase inhibitory activities in plasma and urine samples following simvastatin (SV) administration. The assay was performed on Tecan Genesis 150 and 200 systems equipped with 8-probe and 96-well plates. Plasma samples containing HMG-CoA reductase inhibitors were treated with acetonitrile for protein precipitation before being incubated with HMG-CoA reductase, [14C]-HMG-CoA, and NADPH for a fixed length of time at a fixed temperature. The product, [14C]-mevalonic acid, was lactonized and separated from excess substrate via a small ion exchange resin column, and radioactivity was counted on a scintillation counter. HMG-CoA reductase inhibitors were measured before and after base hydrolysis. The two values obtained for each sample are referred to as 'active' and 'total' HMG-CoA reductase inhibitor concentrations. Simvastatin acid (SVA), the beta-hydroxy acid of SV, was used as a standard to generate a calibration curve of HMG-CoA reductase activity versus SVA concentration (ng/ml). Three calibration ranges, 0.4-20, 2-50, and 50, 100 ng/ml, in human and animal plasma and urine were validated. The assay precision was less than 8.5%, CV in plasma and less than 10.4% in urine. The assay accuracy was 93.6-103.0 and 98.1-103.9% for the 0.4 20 and 2-50 ng/ml calibration ranges, respectively, in human plasma, and was 97.3-105.1, 94.4- 105.2, and 90.2-95.7%, for calibration range 5-100 ng/ml in rat plasma, dog plasma and human urine, respectively.     

Determination of an echinocandin, MK-0991, in mammalian plasma by radioimmunoassay

A quantitative method based on radioimmunoassay for the determination of the antifungal agent, CANCIDAS™ (MK-0991) has been developed and validated. The immunogen was prepared by coupling MK-0991 to bovine serum albumin through a two-step reaction with difluorodinitrobenzene. An antiserum specific to MK-0991 was selected for RIA. The assay was based on the competitive immunoassay principle in which the drug competes with iodinated drug for a limited quantity of specific antibody. The bound tracer was separated via goat anti-rabbit globulin. The assay demonstrates good accuracy and reproducibility at plasma concentration down to 10 ng/ml. The specificity of the RIA method was confirmed by cross-validating against an established HPLC method.     

Is supplemental regional anesthesia associated with more complications and readmissions after ankle fracture surgery in the inpatient and outpatient setting?

BackgroundThere is concern that regional anesthesia is associated with increased risk of complications, including return to the hospital for uncontrolled pain once the regional anesthetic wears off.MethodsRetrospective database review of patients who underwent open reduction and internal fixation of a closed ankle fracture from 2014–16 who received general anesthesia alone (GA) or general anesthesia plus regional anesthesia (RA).Results9459 patients met inclusion criteria. Patients in the RA group had significantly longer operative duration in both inpatient (GAI = 71 min vs RAI = 79 min, p = 0.002) and outpatient setting (GAO = 66 min vs RAI = 72 min, p < 0.001), lower overall LOS (GA = 1.7 days vs RA = 1.1 days, p < 0.001), and higher readmission rate for pain (RAO = 4 [0.3%] vs GAO = 1 [0.0%], p = 0.007).ConclusionsPatients who received supplemental regional anesthesia had shorter hospital LOS, increased operative time, and increased readmission rates for rebound pain. However, the small number of patients needing readmission are not clinically significant demonstrating that regional anesthesia is safe, effective and readmission for rebound pain should not be a concern.Level of EvidenceIII.     

Usefulness of selected circulating biochemical markers in diagnosis and monitoring of endometriosis]

A review of the literature for searching of biochemical marker of endometriosis is presented. The investigations with CA 125, antiendometrial antibodies, placental protein 14 and others have not established a sensitive screening test for predicting endometriosis, especially in early stages of the disease. Most authors confirm usefulness of those markers in monitoring therapy and predicting recurrences. This may allow to avoid commonly performed "second look" laparoscopy.     

Über absteigende Hinterstrangsdegeneration

Ohne ZusammenfassungHierzu Taf. I und II.