Effect of bimatoprost sustained-release intracameral implant on intraocular pressure and medication burden in patients with prior glaucoma surgery.

The present retrospective study evaluated intraocular pressure (IOP) and medication burden after bimatoprost sustained-release (bimatoprost SR, Durysta, Allergan) implantation in patients with glaucoma. A secondary objective was to examine an effect of bimatoprost SR in a subset of patients with prior minimally invasive and incisional glaucoma surgery. A retrospective chart review of 122 eyes that received bimatoprost SR by 6 glaucoma specialists at Wills Eye Hospital between March 2020 and September 2021 was performed. One hundred and eighteen eyes from 84 patients had a reduction in IOP (18.5±5.7mmHg vs. 16.0±5.4mmHg, P<0.01) and required fewer glaucoma medications (2.1±1.4 vs. 1.2±1.2, P<0.01) after bimatoprost SR implantation. In 41 eyes from 31 patients who previously underwent glaucoma surgery (including iStent, goniotomy, trabeculectomy, Xen Gel Stent, or tube shunt surgery), medication burden was decreased after bimatoprost SR implantation (1.9±1.3 vs. 1.0±1.0, P<0.001). These data suggest that bimatoprost SR is an efficacious treatment modality for glaucoma, even in post-surgical patients.

HAPPILEE: HAPPE In Low Electrode Electroencephalography, a standardized pre-processing software for lower density recordings.

Lower-density Electroencephalography (EEG) recordings (from 1 to approximately 32 electrodes) are widely-used in research and clinical practice and enable scalable brain function measurement across a variety of settings and populations. Though a number of automated pipelines have recently been proposed to standardize and optimize EEG pre-processing for high-density systems with state-of-the-art methods, few solutions have emerged that are compatible with lower-density systems. However, lower-density data often include long recording times and/or large sample sizes that would benefit from similar standardization and automation with contemporary methods. To address this need, we propose the HAPPE In Low Electrode Electroencephalography (HAPPILEE) pipeline as a standardized, automated pipeline optimized for EEG recordings with lower density channel layouts of any size. HAPPILEE processes task-free (e.g., resting-state) and task-related EEG (including event-related potential data by interfacing with the HAPPE+ER pipeline), from raw files through a series of processing steps including filtering, line noise reduction, bad channel detection, artifact correction from continuous data, segmentation, and bad segment rejection that have all been optimized for lower density data. HAPPILEE also includes post-processing reports of data and pipeline quality metrics to facilitate the evaluation and reporting of data quality and processing-related changes to the data in a standardized manner. Here the HAPPILEE steps and their optimization with both recorded and simulated EEG data are described. HAPPILEE's performance is then compared relative to other artifact correction and rejection strategies. The HAPPILEE pipeline is freely available as part of HAPPE 2.0 software under the terms of the GNU General Public License at: https://github.com/PINE-Lab/HAPPE.

Time-frequency approaches to investigating changes in feedback processing during childhood and adolescence.

Processing feedback from the environment is an essential function during development to adapt behavior in advantageous ways. One measure of feedback processing, the feedback negativity (FN), is an ERP observed following the presentation of feedback. Findings detailing developmental changes in the FN have been mixed, possibly due to limitations in traditional ERP measurement methods. Recent work shows that both theta and delta frequency activity contribute to the FN; utilizing time-frequency methods to measure change in power and phase in these frequency bands may provide more accurate representation of feedback processing development in childhood and adolescence. We employ time-frequency power and intertrial phase synchrony measures, in addition to conventional time-domain ERP methods, to examine the development of feedback processing in the theta (4-7 Hz) and delta (.1-3 Hz) bands throughout adolescence. A sample of 54 female participants (8-17 years old) completed a gambling task while EEG was recorded. As expected, time-domain ERP amplitudes showed no association with age. In contrast, significant effects were observed for the time-frequency measures, with theta power decreasing with age and delta power increasing with age. For intertrial phase synchrony, delta synchrony increased with age, while age-related changes in theta synchrony differed for gains and losses. Collectively, these findings highlight the importance of considering time-frequency dynamics when exploring how the processing of feedback develops through late childhood and adolescence. In particular, the role of delta band activity and theta synchrony appear central to understanding age-related changes in the neural response to feedback.

Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers.

Tobacco smoking remains the leading cause of preventable death worldwide and current smoking cessation medications have limited efficacy. Thus, there is a clear need for translational research focused on identifying novel pharmacotherapies for nicotine addiction. Our previous studies demonstrated that acute administration of an acetylcholinesterase inhibitor (AChEI) attenuates nicotine taking and seeking in rats and suggest that AChEIs could be repurposed for smoking cessation. Here, we expand upon these findings with experiments designed to determine the effects of repeated AChEI administration on voluntary nicotine taking in rats as well as smoking behavior in human smokers. Rats were trained to self-administer intravenous infusions of nicotine (0.03 mg kg(-1) per 0.59 ml) on a fixed-ratio-5 schedule of reinforcement. Once rats maintained stable nicotine taking, galantamine or donepezil was administered before 10 consecutive daily nicotine self-administration sessions. Repeated administration of 5.0 mg kg(-1) galantamine and 3.0 mg kg(-1) donepezil attenuated nicotine self-administration in rats. These effects were reinforcer-specific and not due to adverse malaise-like effects of drug treatment as repeated galantamine and donepezil administration had no effects on sucrose self-administration, ad libitum food intake and pica. The effects of repeated galantamine (versus placebo) on cigarette smoking were also tested in human treatment-seeking smokers. Two weeks of daily galantamine treatment (8.0 mg (week 1) and 16.0 mg (week 2)) significantly reduced smoking rate as well as smoking satisfaction and reward compared with placebo. This translational study indicates that repeated AChEI administration reduces nicotine reinforcement in rats and smoking behavior in humans at doses not associated with tolerance and/or adverse effects.

Delayed Gadolinium-Enhanced MR Imaging of Cartilage (dGEMRIC) following ACL injury.

OBJECTIVE: Early detection of glycosaminoglycan (GAG) loss may provide insight into mechanisms of cartilage damage in the anterior cruciate ligament (ACL)-injured patient. We hypothesized that tibial and femoral Delayed Gadolinium-Enhanced MR Imaging of Cartilage (dGEMRIC) indices would be lower in the medial compartment of the ACL-injured knee than in the contralateral, uninjured knee, and that scan order (i.e., whether the injured or the uninjured knee was imaged first) would not affect the indices. METHODS: 15 subjects with unilateral ACL injuries received a double dose of gadolinium [Gd(DTPA)(2-)] intravenously. After 90 min, both knees were sequentially imaged. The injured knee was scanned first in the odd-numbered subjects and second in the even-numbered subjects. The dGEMRIC indices of the median slice of the medial compartment were determined using the MRIMapper software. Index comparisons were made between knee status (ACL-injured vs uninjured), scan order (ACL-injured first vs uninjured first), and cartilage location (tibia vs femur) using a mixed model. RESULTS: There was a significant difference in the mean dGEMRIC indices of the medial compartment between injured and uninjured knees (P<0.007). On average, there was a 13% decrease in the dGEMRIC index of the injured knee compared to the uninjured knee. There were no significant effects due to test order (P=0.800) or cartilage location (P=0.439). CONCLUSIONS: The results demonstrate lower GAG concentrations in the medial compartment of the femoral and tibial articular cartilage of the ACL-injured knee when compared to the contralateral uninjured knee. The dGEMRIC indices were not sensitive to scan order; thus, sequential imaging of both knees is possible in this patient population.

Quantitative MR imaging using "LiveWire" to measure tibiofemoral articular cartilage thickness.

OBJECTIVE: To assess the reliability and accuracy of manual and semi-automated segmentation methods for quantifying knee cartilage thickness. This study employed both manual and LiveWire-based semi-automated segmentation methods, ex vivo and in vivo, to measure tibiofemoral (TF) cartilage thickness. METHODS: The articular cartilage of a cadaver knee and a healthy volunteer's knee were segmented manually and with LiveWire from multiple 3T MR images. The cadaver specimen's cartilage thickness was also evaluated with a 3D laser scanner, which was assumed to be the gold standard. Thickness measurements were made within specific cartilage regions. The reliability of each segmentation method was assessed both ex vivo and in vivo, and accuracy was assessed ex vivo by comparing segmentation results to those obtained with laser scanning. RESULTS: The cadaver specimen thickness measurements showed mean coefficients of variation (CVs) of 4.16%, 3.02%, and 1.59%, when evaluated with manual segmentation, LiveWire segmentation, and laser scanning, respectively. The cadaver specimen showed mean absolute errors versus laser scanning of 4.07% and 7.46% for manual and LiveWire segmentation, respectively. In vivo thickness measurements showed mean CVs of 2.71% and 3.65% when segmented manually and with LiveWire, respectively. CONCLUSIONS: Manual segmentation, LiveWire segmentation, and laser scanning are repeatable methods for quantifying knee cartilage thickness; however, the measurements are technique-dependent. Ex vivo, the manual segmentation error was distributed around the laser scanning mean, while LiveWire consistently underestimated laser scanning by 8.9%. Although LiveWire offers repeatability and decreased segmentation time, manual segmentation more closely approximates true cartilage thickness, particularly in cartilage contact regions.

Effects of ACL interference screws on articular cartilage volume and thickness measurements with 1.5 T and 3 T MRI.

OBJECTIVE: To assess the effects of interference screws, which are commonly used to surgically fix an anterior cruciate ligament (ACL) graft in the ACL-deficient knee, and magnetic field strength on cartilage volume and thickness measurements with quantitative magnetic resonance imaging (qMRI). METHODS: Five cadaver knees were imaged using a cartilage-sensitive sequence (T1-weighted water-excitation, three-dimensional (3D) fast low-angle shot) on 1.5T and 3T scanners with and without interference screws implanted. The tibiofemoral articular cartilage was segmented and reconstructed from the magnetic resonance images, and volume and thickness measurements were made on the resulting 3D models. RESULTS: Although several load-bearing regions showed significant differences in volume and thickness between magnet strengths, most showed no significant difference between screw conditions. The medial tibial cartilage showed a mean decrease in volume of 5.9% and 8.0% in the presence of interference screws at 3T and 1.5T, respectively. At 3T and 1.5T, the medial tibial cartilage showed a mean decrease in thickness of 7.0% and 12.0%, respectively, in the presence of interference screws. CONCLUSIONS: Caution should be used when interpreting thickness and volume of cartilage at 3T in the presence of interference screws, particularly in the medial tibial compartment. Additionally, 3T and 1.5T qMRI should not be used interchangeably to assess structural changes in tibiofemoral articular cartilage during longitudinal studies.