Language lateralization shifts with learning by adults.

For the majority of the population, language is a left-hemisphere lateralized function. During childhood, a pattern of increasing left lateralization for language has been described in brain imaging studies, suggesting that this trait develops. This development could reflect change due to brain maturation or change due to skill acquisition, given that children acquire and refine language skills as they mature. We test the possibility that skill acquisition, independent of age-associated maturation can result in shifts in language lateralization in classic language cortex. We imaged adults exposed to an unfamiliar language during three successive fMRI scans. Participants were then asked to identify specific words embedded in Norwegian sentences. Exposure to these sentences, relative to complex tones, resulted in consistent activation in the left and right superior temporal gyrus. Activation in this region became increasingly left-lateralized with repeated exposure to the unfamiliar language. These results demonstrate that shifts in lateralization can be produced in the short term within a learning context, independent of maturation.

Systematic literature review of lymphatic imaging-guided procedural management of Noonan syndrome.

OBJECTIVES: To assess through literature case analysis how advances in lymphatic imaging, interventional radiology, and lymphatic vascular microsurgery illuminate and improve the lymphatic-flow status in select patients with Noonan syndrome (NS) who have undergone surgical intervention as a part of their comprehensive and individualized treatment plan. Also, we sought to illustrate the spectrum of lymphatic complications that can occur in this patient population when lymphatic flow through abnormal vasculature is surgically disrupted. METHODS: A literature review was performed by searching "Noonan AND Lymphatic AND Imaging" in the PubMed database. Inclusion criteria for this study were (1) diagnosis and clinical description of at least one original patient with NS, (2) imaging figures depicting lymphatic structure and function or a description of lymphatic imaging findings when a figure is not present, and (3) documentation of either lymphatic surgical intervention or lymphatic complications resulting from other procedures. Patient cases were first grouped by documented surgical intervention type, then clinical outcomes and lymphatic imaging results were compared. RESULTS: A total of 18 patient cases from 10 eligible publications were included in our review. Lymphatic imaging findings across all patients included lymphatic vessel dysplasia along with flow disruption (n = 16), thoracic duct malformations (n = 12), dermal lymphatic reflux (n = 7), and dilated lymphatic vessels (n = 4). Lymphovenous anastomosis (n = 4) resulted in rapid improvement of patient symptoms and signs. New-onset lymphatic manifestations noted over 10 to 20 years for two of these patients were chylothorax (n = 1), erysipelas (n = 1), and gradual-onset nonchylous scrotal lymphorrhea (n = 1). Targeted endovascular lymphatic disruption via sclerosis, embolization, or ablation (n = 8) results were mixed depending on the degree of central lymphatic involvement and included resolution of symptoms (n = 1), postoperative abdominal hemorrhage (n = 1), stable condition or minor improvement (n = 5), and death (n = 2). Large lymphatic vessel ligation or accidental incision (n = 6) occurred during thoracotomy (n = 4), scrotoplasty (n = 1), or inguinal lymph node biopsy (n = 1). These resulted in postoperative onset of new-onset regional lymphatic reflux (n = 5), chylothorax (n = 4), death (n = 3), or persistent or unchanged symptoms (n = 1). CONCLUSIONS: Imaging of the central lymphatics enabled characterization of lymphatic developmental features and guided operative management of lymphatic vascular defects in patients with NS. This review of the literature suggests that the surgical preservation or enhancement of central lymphatic return in patients with NS may improve interventional outcomes, whereas the disruption of central lymph flow has significant potential to cause severe postoperative complications and worsening of the patient's clinical condition.

Amyloid-ß disrupts unitary calcium entry through endothelial NMDA receptors in mouse cerebral arteries.

Transient increases in intracellular Ca2+ activate endothelium-dependent vasodilatory pathways. This process is impaired in cerebral amyloid angiopathy, where amyloid-ß(1-40) accumulates around blood vessels. In neurons, amyloid-ß impairs the Ca2+-permeable N-methyl-D-aspartate receptor (NMDAR), a mediator of endothelium-dependent dilation in arteries. We hypothesized that amyloid-ß(1-40) reduces NMDAR-elicited Ca2+ signals in mouse cerebral artery endothelial cells, blunting dilation. Cerebral arteries isolated from 4-5 months-old, male and female cdh5:Gcamp8 mice were used for imaging of unitary Ca2+ influx through NMDAR (NMDAR sparklets) and intracellular Ca2+ transients. The NMDAR agonist NMDA (10 µmol/L) increased frequency of NMDAR sparklets and intracellular Ca2+ transients in endothelial cells; these effects were prevented by NMDAR antagonists D-AP5 and MK-801. Next, we tested if amyloid-ß(1-40) impairs NMDAR-elicited Ca2+ transients. Cerebral arteries incubated with amyloid-ß(1-40) (5 µmol/L) exhibited reduced NMDAR sparklets and intracellular Ca2+ transients. Lastly, we observed that NMDA-induced dilation of pial arteries is reduced by acute intraluminal amyloid-ß(1-40), as well as in a mouse model of Alzheimer's disease, the 5x-FAD, linked to downregulation of Grin1 mRNA compared to wild-type littermates. These data suggest that endothelial NMDAR mediate dilation via Ca2+-dependent pathways, a process disrupted by amyloid-ß(1-40) and impaired in 5x-FAD mice.

Postmortem tissue concentrations of olanzapine.

Twenty-eight cases from 2004-2007 involving olanzapine were analyzed at the San Diego County Medical Examiner's Office. Olanzapine was initially detected by gas chromatography coupled with mass spectrometry (GC-MS), and then confirmed by GC with a nitrogen-phosphorus detector. In cases where olanzapine was detected, concentrations in peripheral blood (PB), central blood (CB), liver, and vitreous were determined if available. In the six olanzapine-only deaths, average olanzapine concentrations (mean+/-standard deviation) were 3.2+/-2.0 mg/L (PB), 4.5+/-2.6 mg/L (CB), 40+/-29 mg/kg (liver), and 1.6+/-0.50 mg/L (vitreous). This was compared to the 10 non-olanzapine-related deaths, which showed average olanzapine concentrations of 0.26+/-0.13 mg/L (PB), 0.29+/-0.17 mg/L (CB), 5.6+/-5.6 mg/kg (liver), and 0.24+/-0.38 mg/L (vitreous). The remaining 10 multi-drug deaths had average concentrations of 0.59+/-0.33 mg/L (PB), 0.64+/-0.60 mg/L (CB), 5.9+/-4.3 mg/kg (liver), and 0.78+/-0.91 mg/L (vitreous). Concentrations of olanzapine associated with toxicity were found to be in the range of 1.4-6.2 mg/L (PB), 1.1-7.4 mg/L (CB), 14-88 mg/kg (liver), and 1.1-2.1 mg/L (vitreous). Concentrations associated with therapeutic use were found to be in the range of 0.11-0.43 mg/L (PB), 0-0.53 mg/L (CB), 0-8.6 mg/kg (liver), and 0-0.98 mg/L (vitreous). Deaths attributed solely to olanzapine were distinguished by a 10-fold or more increase in tissue concentrations over those found in the non-olanzapine-related deaths.

An fMRI study of implicit language learning in developmental language impairment.

Individuals with developmental language impairment can show deficits into adulthood. This suggests that neural networks related to their language do not normalize with time. We examined the ability of 16 adults with and without impaired language to learn individual words in an unfamiliar language. Adults with impaired language were able to segment individual words from running speech, but needed more time to do so than their normal-language peers. ICA analysis of fMRI data indicated that adults with language impairment activate a neural network that is comparable to that of adults with normal language. However, a regional analysis indicated relative hyperactivation of a collection of regions associated with language processing. These results are discussed with reference to the Statistical Learning Framework and the sub-skills thought to relate to word segmentation.

Neural Correlates of Morphology Acquisition through a Statistical Learning Paradigm.

The neural basis of statistical learning as it occurs over time was explored with stimuli drawn from a natural language (Russian nouns). The input reflected the "rules" for marking categories of gendered nouns, without making participants explicitly aware of the nature of what they were to learn. Participants were scanned while listening to a series of gender-marked nouns during four sequential scans, and were tested for their learning immediately after each scan. Although participants were not told the nature of the learning task, they exhibited learning after their initial exposure to the stimuli. Independent component analysis of the brain data revealed five task-related sub-networks. Unlike prior statistical learning studies of word segmentation, this morphological learning task robustly activated the inferior frontal gyrus during the learning period. This region was represented in multiple independent components, suggesting it functions as a network hub for this type of learning. Moreover, the results suggest that subnetworks activated by statistical learning are driven by the nature of the input, rather than reflecting a general statistical learning system.

Comparison of Immediate and Delayed Blood Alcohol Concentration Testing.

The effects of storage time and temperature on blood alcohol concentration were evaluated in this two-part study involving 34 ethanol-negative and 21 ethanol-positive volunteers. Multiple 10-mL Vacutainer(®) blood tubes containing 100 mg of sodium fluoride and 20 mg of potassium oxalate were collected from living persons and subjected to various storage conditions. The time from collection to analysis ranged from 0 to 60 days and storage temperatures ranged from 3 to 20°C. Regardless of the storage conditions, all ethanol-negative samples remained negative (<0.0025 g/100 mL) throughout the study. There was no increase in the concentration of ethanol-positive samples beyond the expected variability of the method, regardless of storage time or temperature. Many ethanol-positive samples demonstrated decreases in concentration during storage compared with the original immediate analysis. The findings from this study support previous research, which demonstrates that microbial formation of ethanol in properly collected antemortem blood is unlikely.