Intravesical electromotive drug administration of mitomycin-C for non-muscle invasive bladder cancer

This article reviews intravesical application of electromotive drug administration (EMDA) for the treatment of bladder cancer and the evidence in support of intravesical passive diffusion chemotherapy in the management of non-muscle invasive bladder cancer. Two recently published randomised trials adopting protocols that use EMDA to enhance urothelial transport of intravesical mitomycin-C showed it provided a therapeutical advantage and suggested that intravesical passive diffusion administration of chemothera-peutic drugs may be suboptimal. Further studies are required to demonstrate feasibility and advantage of intravesical EMDA of mitomycin-C in the wider uro-oncological community

EEG Theta Power Activity Reflects Workload among Army Combat Drivers: An Experimental Study

We thank Héctor Rieiro, Eduardo Bailon, and Jose M. Morales, (University of Granada) for their help in data processing. We also thank Lieutenant Colonel Francisco de Asís Vázquez Prieto (Training and Doctrine Command, Spanish Army) for his help in organizing the study.We aimed to evaluate the effects of mental workload variations, as a function of the road environment, on the brain activity of army drivers performing combat and non-combat scenarios in a light multirole vehicle dynamic simulator. Forty-one non-commissioned officers completed three standardized driving exercises with different terrain complexities (low, medium, and high) while we recorded their electroencephalographic (EEG) activity. We focused on variations in the theta EEG power spectrum, a well-known index of mental workload. We also assessed performance and subjective ratings of task load. The theta EEG power spectrum in the frontal, temporal, and occipital areas were higher during the most complex scenarios. Performance (number of engine stops) and subjective data supported these findings. Our findings strengthen previous results found in civilians on the relationship between driver mental workload and the theta EEG power spectrum. This suggests that EEG activity can give relevant insight into mental workload variations in an objective, unbiased fashion, even during real training and/or operations. The continuous monitoring of the warfighter not only allows instantaneous detection of over/underload but also might provide online feedback to the system (either automated equipment or the crew) to take countermeasures and prevent fatal errors.This work was supported by Santander Bank–CEMIX UGR-MADOC (grant number PINs2018-15 to CDP & LLDS) and the Centro Universitario de la Defensa–Zaragoza (grant numbers 2015-05 and 2017-03 to MVS). Additional support was obtained from the Unit of Excellence on Brain, Behavior, and Health (SC2), funded by the Excellence actions program of the University of Granada. The funding organizations had no role in the design or conduct of this research. Research by LLDS is supported by the Ramón y Cajal fellowship program from the Spanish State Research Agency (RYC-2015-17483)

Oculomotor Assessment of Diurnal Arousal Variations

Saccadic and pupillary responses are reliable indices of arousal decrement (e.g. fatigue), that might be exploited to improve work schedule guidelines. In this study, we tested the sensitivity of a short 30-s oculomotor test to detect diurnal arousal variations. Twelve participants (5 females, 7 males, 37.7+-11.9 years) volunteered to be assessed every hour (66+-20 min) for three consecutive working days, during their regular office-hours. We used a fully automated testing system, the FIT 2000 Fitness Impairment Tester (Pulse Medical Instruments Inc., Rockville, MD, USA), to measure and record saccadic peak velocity, pupil diameter, and latency and amplitude of the pupillary light reflex. In addition, we collected subjective levels of arousal using the Stanford Sleepiness Scale, and body core temperature. We analyzed the data using a linear mixed model approach for longitudinal data. Both saccadic velocity and subjective alertness decreased over the course of a day, while body core temperature increased (all p-values.05). The data also weakly suggested an increase of the pupil diameter (p 07). The findings support the use of oculomotor indices in the assessment of arousal and fatigue in applied settings

The influence of LED road stud color on driver behavior and perception along horizontal curves at nighttime

Scotopic lighting conditions (reduced level of natural light or presence of artificial lighting) may impair driving performance and, therefore, impact on road safety. Thanks to technological developments, low-cost light emitting diode (LED) studs are now being considered as an alternative and affordable pavement marking solution to assist drivers in these conditions. By helping them to maintain their vehicle within the marked lane, the studs should prevent any deterioration in driver performance when negotiating curves at nighttime. However, the few studies that investigated the impact of LED studs on driving performance produced inconsistent results, and the question of whether they actively improve driver performance remains open. Furthermore, while international road regulations allow the use of LED studs, they do not provide consistent prescriptions for their lighting color.Here, we assessed the influence of different LED lighting colors (red, white, and unlit) on longitudinal and transversal driver behavior when negotiating road curves with different radii and sense of direction. In the study, thirty-six drivers drove a dynamic virtual scenario featuring twenty-four curves. After the driving simulation, participants completed a static perception test in which they assessed each curve in terms of the perceived levels of risk, pleasantness, and arousal they experienced while driving on it.In comparison with the unlit and red lit curves, those marked with white lighting LED studs were perceived as less risky, less arousing, and more pleasant independently of the radii and curve direction. Furthermore, when entering these curves, participants tended to shift their driving trajectories towards the center of the road. This effect was most evident on the central part of the curve. Further studies are expected to corroborate these results by focusing on different road geometries and LED stud layouts, as well as testing driving behavior in controlled road field studies

Test-Retest Reliability and Minimum Detectable Change for Various Frontal Plane Projection Angles during Dynamic Tasks

Objective: Establish between-day test-retest reliability metrics for 2-dimensional frontal plane projection angles (FPPAs) during the lateral step-down (LSD), single-limb squat (SLS), single-limb landing (SLL), and drop vertical jump (DVJ). Design: Test-retest reliability study Setting: University laboratory Participants: 20 healthy adults (12 female, age = 23.60±1.93 years old, body mass index = 24.26±2.54 kg/m2) were tested on 2 separate occasions 7-14 days apart. Main Outcome Measures: Intraclass correlation coefficients (ICC), standard errors of the measurement (SEM), and minimal detectable change (MDC) values across the LSD, SLS, SLL, and DVJ for the following body region variables: trunk, trunk on pelvis, pelvis, hip, thigh to vertical, knee, and shank to vertical. Results: There was moderate-to-substantial between-day test-retest reliability for nearly all body regions across all tasks (ICC = 0.65-0.96). SEM values varied across body regions and tasks (0.9-3.5 degrees). MDCs were variable (2.3-9.8 degrees). Of the body regions, MDCs were largest for the knee and hip. By task, MDCs were lowest for the LSD. Conclusions: This study identified between-day test-retest reliability metrics for 2-dimensional FPPAs across a variety of body regions during commonly assessed clinical tasks. These data allow clinicians and researchers to more confidently assess true change between assessments or over time

The effect of traffic light spacing and signal congruency on drivers’ responses at urban intersections

Traffic lights are critical in regulating traffic flow and modulate the level of service and road user safety. As suggested by studies conducted with pedestrians, traffic light spacing and signal congruency could also impact a driver's decision-making process. However, requirements related to designing signalized intersections do not always consider the spacing between two consecutive traffic lights or the congruency of the information displayed. Here, using a classic traffic psychology paradigm, we developed a hybrid Go/No-go Flanker PC-based task to explore how traffic light spacing and signal congruency modulate drivers’ decisions in urban intersections. Real images of road intersections were edited to reproduce two specific conditions between traffic lights. Specifically, we manipulated both spacing (short vs. long) and congruency (congruent [e.g., red-red/green-green steady light] vs. incongruent [e.g., red-green/green-red steady light]). We found that incongruent information, displayed on short spacing traffic signals, delayed drivers’ responses without being detrimental to their decision-making processes. The results of this exploratory study could offer guidance to transportation engineers to simplify traffic light information readability and increase drivers’ awareness of traffic conditions and road safety

Intravesical oxybutynin: mode of action assessed by passive diffusion and electromotive administration with pharmacokinetics of oxybutynin and N-desethyl oxybutynin.

PURPOSE: A proportion of patients with detrusor hyperreflexia who are unresponsive to oral oxybutynin often benefit from intravesical oxybutynin instillation. To our knowledge the precise mode of action of this method is obscure. MATERIALS AND METHODS: In 12 patients with detrusor hyperreflexia who were previously unresponsive to oral and intravesical passive diffusion of 5 mg. oxybutynin we administered 5 mg. oxybutynin orally as well as increased doses of 15 mg. oxybutynin intravesically with passive diffusion and with 15 mA. associated electric current. Each administration mode per patient was associated with an 8-hour urodynamic monitoring session during which oxybutynin and N-desethyl oxybutynin plasma levels, and intravesical oxybutynin uptake were measured. RESULTS: A dose of 5 mg. oxybutynin orally induced no urodynamic improvement with an area under the plasma concentration time curve of combined N-desethyl oxybutynin plus oxybutynin of 16,297 ng./8 hours and an area under the curve ratio of N-desethyl oxybutynin-to-oxybutynin of 11:1. Passive diffusion oxybutynin resulted in 12 mg. oxybutynin intravesical uptake and significant improvement in 3 of 8 urodynamic measurements, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was only 2,123 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was 1.1:1.0. Electromotive administration of oxybutynin resulted in almost complete intravesical uptake of the 15 mg. dose, significant improvement in all 8 urodynamic measurements and an increased oxybutynin level versus oral and passive diffusion, although the area under the curve of combined N-desethyl oxybutynin plus oxybutynin was 4,574 ng./8 hours and the N-desethyl oxybutynin-to-oxybutynin ratio was inverted at 1.0:1.4. The oral dose of 5 mg. oxybutynin caused anticholinergic side effects in 8 of the 12 patients. Neither intravesical passive diffusion nor electromotive administration caused side effects with an uptake of 12 and 15 mg., respectively. CONCLUSIONS: A large proportion of intravesical oxybutynin is sequestered, probably in the urothelium. Intravesical oxybutynin administration confers therapeutic benefits via localized direct action within the bladder wall. Comment in Intravesical treatment of bladder dysfunction. [J Urol. 2001

A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes

Multimodality probes appear of great interest for innovative imaging applications in disease diagnosis. Herein, we present a chemical strategy enabling site-specific doublemodification and cyclization of a peptide probe exploiting native chemical ligation (NCL) and thiol-maleimide addition. The synthetic strategy is straightforward and of general applicability for the development of double-labeled peptide multimodality probes