Objective: This retrospective analysis of electrocardiographic (ECG) data investigated the cardiovascular effects of paroxetine 10-50 mg/day in pediatric patients (7-18 years of age). Data were ...collected from three 8- to 10-week, randomized, placebo-controlled, double-blind trials of paroxetine in pediatric patients with major depressive disorder or obsessive-compulsive disorder. Method: Electrocardiograms (ECGs) were retrospectively retrieved from 63 study sites in the United States and Canada. Only patients with at least one screening and one on-treatment ECG were included. ECGs were analyzed for heart rate, QT interval corrected using Bazett's formula (QTcB) and Fridericia's formula (QTcF), at screening and while being treated. PR, R-R, and QRS intervals and the maximum change in QTcB and QTcF from screening to endpoint were determined. Clinically significant thresholds were defined a priori. Results: A total of 1,451 ECGs from 449 patients receiving placebo (n = 207), paroxetine (n = 200), or imipramine (n = 42) were analyzed. Treatment with paroxetine did not significantly increase QTcB or QTcF or any ECG parameters compared with placebo. Treatment with imipramine significantly increased heart rate and QTcB, R-R, and QRS intervals compared with either paroxetine or placebo. Conclusions: Data from this retrospective study indicate that paroxetine (10-50 mg/day) is unlikely to be associated with significant ECG changes in medically healthy pediatric patients. (Contains 4 tables.)
Event-related brain potentials (ERPs) recorded during presentation of a series of words or pictures show enhanced positivity between 300 and 800 ms after presentation of repeated items. However, ...little attention has been directed to the characterization of this ERP recognition memory effect using auditory stimuli. The present study directly compared the ERP ‘old/new effect’ for words presented in the visual and auditory modalities. Nose-referenced ERPs were recorded from 30 electrode sites while participants (
N=16) were engaged in visual and auditory continuous word recognition memory tasks. Spatially and temporally overlapping ERP components were identified and measured by covariance-based principal components analysis. The expected old/new effect was observed in both modalities, with a comparable time course peaking at 560 ms, but having a more anterior scalp topography for visual items. This suggests a common cognitive process (i.e. successful retrieval of information from memory) associated with separable neural generators in each modality. Despite this temporal synchronization, the old/new effect overlapped ERP components having distinct scalp topographies (N2) or peak latencies (P3) for each modality. The positive-going old/new effect was preceded by an earlier negativity peaking at 370 ms that was greater across modalities for old than new words, likely reflecting semantic processing aspects of word recognition memory. A late (beyond 900 ms), broadly-distributed negativity was also greater for old than new words, prolonged for auditory items, and may represent activity of a post-retrieval process.
Brain event-related potential (ERP) studies of recognition memory have consistently shown that correctly identified old items elicit greater positivity than new items. This is referred to as the old .../new effect & is argued to reflect processes related to memory retrieval. To date, there have been no ERP studies of recognition memory that have directly compared the old/new effect in the visual & auditory modalities. In this study, ERPs were recorded from 30 electrode sites while participants (n = 16) were engaged in visual & auditory continuous word recognition memory tasks. The expected old/new effect, with greater late positivity to correctly recognized old words was observed in both modalities, although scalp topography was significantly different. While the visual old /new effect was restricted to midline sites & maximal over the parietal region, the auditory old/new effect involved more lateral sites & was maximal over the occipital region. The timing of the old/new effect was the same across modalities with a peak at 600 ms. In addition, old words elicited greater late negativity (1100-1500 ms) over the left hemisphere than new words, suggesting the activation of verbally mediated post-retrieval processes specific to old responses. Overall, the findings suggest that the old/new effect represents a common cognitive mechanism in the two modalities (i.e., successful retrieval of information from memory), & that a different pattern of neural generators contribute to each.
Brain event-related potential (ERP) studies of recognition memory have consistently shown that correctly identified old items elicit greater positivity than new items. This is referred to as the ...old/new effect and is argued to reflect processes related to memory retrieval. To date, there have been no ERP studies of recognition memory that have directly compared the old/new effect in the visual and auditory modalities. In this study, ERPs were recorded from 30 electrode sites while participants (n = 16) were engaged in visual and auditory continuous word recognition memory tasks. The expected old/new effect, with greater late positivity to correctly recognized old words was observed in both modalities, although scalp topography was significantly different. While the visual old/new effect was restricted to midline sites and maximal over the parietal region, the auditory old/new effect involved more lateral sites and was maximal over the occipital region. The timing of the old/new effect was the same across modalities with a peak at 600 ms. In addition, old words elicited greater late negativity (1100–1500 ms) over the left hemisphere than new words, suggesting the activation of verbally mediated post-retrieval processes specific to old responses. Overall, the findings suggest that the old/new effect represents a common cognitive mechanism in the two modalities (i.e., successful retrieval of information from memory), and that a different pattern of neural generators contribute to each.
Event-related brain potentials (ERPs) recorded during presentation of a series of words or pictures show enhanced positivity between 300 and 800 ms after presentation of repeated items. However, ...little attention has been directed to the characterization of this ERP recognition memory effect using auditory stimuli. The present study directly compared the ERP 'old/new effect' for words presented in the visual and auditory modalities. Nose-referenced ERPs were recorded from 30 electrode sites while participants (N=16) were engaged in visual and auditory continuous word recognition memory tasks. Spatially and temporally overlapping ERP components were identified and measured by covariance-based principal components analysis. The expected old/new effect was observed in both modalities, with a comparable time course peaking at 560 ms, but having a more anterior scalp topography for visual items. This suggests a common cognitive process (i.e. successful retrieval of information from memory) associated with separable neural generators in each modality. Despite this temporal synchronization, the old/new effect overlapped ERP components having distinct scalp topographies (N2) or peak latencies (P3) for each modality. The positive-going old/new effect was preceded by an earlier negativity peaking at 370 ms that was greater across modalities for old than new words, likely reflecting semantic processing aspects of word recognition memory. A late (beyond 900 ms), broadly-distributed negativity was also greater for old than new words, prolonged for auditory items, and may represent activity of a post-retrieval process.
This study examined whether adolescents with major depressive disorder (MDD) display the abnormal electroencephalographic (EEG) alpha asymmetries found in depressed adults. Resting EEG was recorded ...in 25 right-handed female outpatients (19 with MDD, 11 of whom also had a current anxiety disorder; 6 with anxiety disorders only) and 10 non-ill controls. In contrast to the non-ill controls, adolescents having MDD but no anxiety disorder showed alpha asymmetry indicative of less activation over right than over left posterior sites. Within the MDD patient group, comorbid anxiety disorders reduced the posterior alpha asymmetry, supporting the potential importance of evaluating anxiety in studies of regional brain activation in adolescent MDD. These preliminary findings are similar to those from adult studies that suggest that MDD is associated with right parietotemporal hypoactivation.
This study examined Karmiloff‐Smith's (1984) model of the development of higher levels of awareness. We extended her model and examined the effects of externally induced representations of a ...successfully completed action on future performance. Fifty‐three children, between the ages of 6 and 8 years, built a bridge to a mountain. After completion, one group drew and verbalized their bridge‐building process, another group only drew, a third group only verbalized and a control group did not rerepresent. The children then built another bridge. Compared to the no‐representation group, children who represented in two modalities tended to increase their spontaneous strategy changes during the second building. The verbal‐only group showed increased spontaneous strategy change relative to no‐representation controls. The draw‐only group decreased this meta‐procedural activity over time compared to the multiple representation group. The bridge constructions were more complex in the second building for the multiple representation group. This study gives support to the possibility of externally stimulating higher levels of awareness in children. Task process change may be understood as a precursor for more substantial change. This study suggests that multiple representations may lead to the greatest flexibility in future performance, and that mode of representation influences meta‐procedural activity.
In vitro models of the blood-brain barrier (BBB) are critical tools for the study of BBB transport and the development of drugs that can reach the CNS. Brain endothelial cells grown in culture are ...often used to model the BBB; however, it is challenging to maintain reproducible BBB properties and function. 'BBB organoids' are obtained following coculture of endothelial cells, pericytes and astrocytes under low-adhesion conditions. These organoids reproduce many features of the BBB, including the expression of tight junctions, molecular transporters and drug efflux pumps, and hence can be used to model drug transport across the BBB. This protocol provides a comprehensive description of the techniques required to culture and maintain BBB organoids. We also describe two separate detection approaches that can be used to analyze drug penetration into the organoids: confocal fluorescence microscopy and mass spectrometry imaging. Using our protocol, BBB organoids can be established within 2-3 d. An additional day is required to analyze drug permeability. The BBB organoid platform represents an accurate, versatile and cost-effective in vitro tool. It can easily be scaled to a high-throughput format, offering a tool for BBB modeling that could accelerate therapeutic discovery for the treatment of various neuropathologies.
The COVID-19 pandemic has revealed the importance of the detection of airborne pathogens. Here, we present composite air filters featuring a bioinspired liquid coating that facilitates the removal of ...captured aerosolized bacteria and viruses for further analysis. We tested three types of air filters: commercial polytetrafluoroethylene (PTFE), which is well known for creating stable liquid coatings, commercial high-efficiency particulate air (HEPA) filters, which are widely used, and in-house-manufactured cellulose nanofiber mats (CNFMs), which are made from sustainable materials. All filters were coated with omniphobic fluorinated liquid to maximize the release of pathogens. We found that coating both the PTFE and HEPA filters with liquid improved the rate at which Escherichia coli was recovered using a physical removal process compared to uncoated controls. Notably, the coated HEPA filters also increased the total number of recovered cells by 57%. Coating the CNFM filters did not improve either the rate of release or the total number of captured cells. The most promising materials, the liquid-coated HEPA, filters were then evaluated for their ability to facilitate the removal of pathogenic viruses via a chemical removal process. Recovery of infectious JC polyomavirus, a nonenveloped virus that attacks the central nervous system, was increased by 92% over uncoated controls; however, there was no significant difference in the total amount of genomic material recovered compared to that of controls. In contrast, significantly more genomic material was recovered for SARS-CoV-2, the airborne, enveloped virus, which causes COVID-19, from liquid-coated filters. Although the amount of infectious SARS-CoV-2 recovered was 58% higher, these results were not significantly different from uncoated filters due to high variability. These results suggest that the efficient recovery of airborne pathogens from liquid-coated filters could improve air sampling efforts, enhancing biosurveillance and global pathogen early warning.
Ecological momentary assessment (EMA) is a methodological approach to studying intraindividual variation over time. This study aimed to use EMA to determine the variability of cognition in ...individuals with chronic stroke, identify the latent classes of cognitive variability, and examine any differences in daily activities, social functioning, and neuropsychological performance between these latent classes.
Participants (
= 202) with mild-to-moderate stroke and over 3-month post-stroke completed a study protocol, including smartphone-based EMA and two lab visits. Participants responded to five EMA surveys daily for 14 days to assess cognition. They completed patient-reported measures and neuropsychological assessments during lab visits. Using latent class analysis, we derived four indicators to quantify cognitive variability and identified latent classes among participants. We used ANOVA and Chi-square to test differences between these latent classes in daily activities, social functioning, and neuropsychological performance.
The latent class analysis converged on a three-class model. The moderate and high variability classes demonstrated significantly greater problems in daily activities and social functioning than the low class. They had significantly higher proportions of participants with problems in daily activities and social functioning than the low class. Neuropsychological performance was not statistically different between the three classes, although a trend approaching statistically significant difference was observed in working memory and executive function domains.
EMA could capture intraindividual cognitive variability in stroke survivors. It offers a new approach to understanding the impact and mechanism of post-stroke cognitive problems in daily life and identifying individuals benefiting from self-regulation interventions.
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