Remote-Use Applications of the ALSFRS-R Clinical Outcome Assessment Tool: A Scoping Review.

OBJECTIVES: In 2021, the U.S. Congress passed the ACT for ALS Act. The law encourages development of "tools, methods, and processes" to improve clinical trial efficiency for neurodegenerative diseases. The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is an outcome measure administered during in-person clinic visits and used to support investigational studies for persons living with Amyotrophic Lateral Sclerosis (PALS). Availability of a standardized, remote-use version of the ALSFRS-R may promote more inclusive, decentralized clinical trials. A scoping literature review was conducted to identify existing remote-use ALSFRS-R tools, synthesize feasibility and comparability of administration modes, and summarize barriers and facilitators to inform development of a standardized remote-use ALSFRS-R tool. METHODS: Included studies reported comparisons between remote and in-person, clinician-reported, ALSFRS-R administration and were published in English (2002-2022). References were identified by searching peer-reviewed and gray literature. Twelve studies met inclusion criteria and were analyzed to compare findings within and across modes of administration. RESULTS: Remote modes of ALSFRS-R administration were categorized into four non-mutually exclusive categories: telephone (n = 6), videoconferencing (n = 3), computer or online platforms (n = 3), mobile-apps and wearables (n = 2), and one unspecified telemedicine modality (n = 1). Studies comparing in-person to telephone or videoconferencing administration reported high ALSFRS-R rating correlations and nonsignificant between- mode differences. CONCLUSION: There is insufficient information in the ALSFRS-R literature to support remote clinician administration for collecting high quality data. Future research should engage PALS, care partners and providers to develop a standardized remote-use ALSFRS-R version.

Physical activity calorie expenditure (PACE) labels in worksite cafeterias: effects on physical activity.

BACKGROUND: Regular physical activity is an important component of healthy living and wellbeing. Current guidelines recommend that adults participate in at least 150 min of moderate or vigorous-intensity physical activity weekly. In spite of the benefits, just over half of U.S. adults meet these recommendations. Calorie-only food labels at points of food purchase have had limited success in motivating people to change eating behaviors and increase physical activity. One new point of purchase approach to promote healthy behaviors is the addition of food labels that display the physical activity requirement needed to burn the calories in a food item (e.g. walk 15 min). METHODS: The Physical Activity Calorie Expenditure (PACE) Study compared activity-based calorie-expenditure food labels with calorie-only labels at three Blue Cross and Blue Shield of North Carolina worksite cafeterias. After 1 year of baseline data collection, one cafeteria had food items labeled with PACE labels, two others had calorie-only food labels. Cohort participants were asked to wear an accelerometer and complete a self-report activity questionnaire on two occasions during the baseline year and twice during the intervention year. RESULTS: A total of 366 study participants were included in the analysis. In the PACE-label group, self-reported physical activity increased by 13-26% compared to the calorie-only label group. Moderate-to-vigorous physical activity (MVPA) increased by 24 min per week in the PACE-label group compared to the calorie-label group (p = 0.06). Changes in accelerometer measured steps, sedentary time, and MVPA had modest increases. Change ranged from 1 to 12% with effect size values from 0.08 to 0.15. Baseline physical activity level significantly moderated the intervention effects for all physical activity outcomes. Participants in both label groups starting in the lowest tertile of activity saw the largest increase in their physical activity. CONCLUSION: Results suggest small positive effects for the PACE labels on self-reported and objective physical activity measures. Minutes of weekly MVPA, strength training, and exercise activities showed modest increases. These results suggest that calorie-expenditure food labels may result in some limited increases in physical activity.

Effect of calories-only vs physical activity calorie expenditure labeling on lunch calories purchased in worksite cafeterias.

BACKGROUND: Calorie labeling on restaurant menus is a public health strategy to guide consumer ordering behaviors, but effects on calories purchased have been minimal. Displaying labels communicating the physical activity required to burn calories may be a more effective approach, but real-world comparisons are needed. METHODS: In a quasi-experimental study, we examined the effect of physical activity calorie expenditure (PACE) food labels compared to calorie-only labels on point-of-decision food purchasing in three worksite cafeterias in North Carolina. After a year of quarterly baseline data collection, one cafeteria prominently displayed PACE labels, and two cafeterias prominently displayed calorie-only labels. Calories from foods purchased in the cafeteria during lunch were assessed over 2 weeks every 3 months for 2 years by photographs of meals. We compared differences in purchased calorie estimates before and after the labeling intervention was introduced using longitudinal generalized linear mixed model regressions that included a random intercept for each participant. RESULTS: In unadjusted models comparing average meal calories after vs before labeling, participants exposed to PACE labels purchased 40.4 fewer calories (P = 0.002), and participants exposed to calorie-only labels purchased 38.2 fewer calories (P = 0.0002). The small difference of 2 fewer calories purchased among participants exposed to PACE labeling vs calorie-only labeling was not significant (P = 0.90). Models adjusting for age, sex, race, occupation, numeracy level, and health literacy level did not change estimates appreciably. CONCLUSION: In this workplace cafeteria setting, PACE labeling was no more effective than calorie-only labeling in reducing lunchtime calories purchased.

NMDA Receptor-Dependent Cholinergic Modulation of Mesolimbic Dopamine Cell Bodies: Neurochemical and Behavioral Studies.

Substance abuse disorders are devastating, costly, and difficult to treat. Identifying the neurochemical mechanisms underlying reinforcement promises to provide critical information in the development of effective treatments. Several lines of evidence suggest that striatal dopamine (DA) release serves as a teaching signal in reinforcement learning, and that shifts in DA release from the primary reward to reward-predicting stimuli play a critical role in the self-administration of both natural and non-natural rewards. However, far less is known about the reinforcing effects of motivationally neutral sensory stimuli, or how these signals can facilitate self-administration behavior. Thus, we trained rats ( n = 7) to perform a visual stimulus-induced instrumental task, which involved lever pressing for activation of a stimulus light. We then microinfused vehicle (phosphate buffered saline), carbachol (acetylcholine receptor agonist), or carbachol in the presence of an N-methyl-d-aspartate (NMDA) receptor-specific drug (NMDA itself, or the antagonist, AP5) into the ventral tegmental area (VTA). This enabled us to directly evaluate how chemical modulation of dopamine cell bodies affects the instrumental behavior, as well as the nature of extracellular dopamine transients recorded in the nucleus accumbens shell (NAc shell) using fast-scan cyclic voltammetry (FSCV). Intra-VTA infusion of carbachol enhanced the magnitude and frequency of dopamine transients in the NAc shell and potentiated active lever responding without altering inactive lever responding, as compared to infusion of vehicle. Coinfusion of carbachol with AP5 abolished dopamine transients recorded in the NAc and attenuated active lever responding without altering inactive lever responding. Finally, coadministration of carbachol and NMDA into the VTA restored both lever pressing and dopaminergic signals recorded in the striatum. Together, these results suggest that acetylcholine and glutamate synergistically act at dopamine cells in the VTA to modulate VTA-NAc shell dopaminergic output, and this underlies motivation to lever press for a motivationally neutral visual stimulus.

Effects of physical activity calorie expenditure (PACE) labeling: study design and baseline sample characteristics.

BACKGROUND: Obesity and physical inactivity are responsible for more than 365,000 deaths per year and contribute substantially to rising healthcare costs in the US, making clear the need for effective public health interventions. Calorie labeling on menus has been implemented to guide consumer ordering behaviors, but effects on calories purchased has been minimal. METHODS: In this project, we tested the effect of physical activity calorie expenditure (PACE) food labels on actual point-of-decision food purchasing behavior as well as physical activity. Using a two-group interrupted time series cohort study design in three worksite cafeterias, one cafeteria was assigned to the intervention condition, and the other two served as controls. Calories from food purchased in the cafeteria were assessed by photographs of meals (accompanied by notes made on-site) using a standardized calorie database and portion size-estimation protocol. Primary outcomes will be average calories purchased and minutes of moderate to vigorous physical activity (MVPA) by individuals in the cohorts. We will compare pre-post changes in study outcomes between study groups using piecewise generalized linear mixed model regressions (segmented regressions) with a single change point in our interrupted time-series study. The results of this project will provide evidence of the effectiveness of worksite cafeteria menu labeling, which could potentially inform policy intervention approaches. DISCUSSION: Labels that convey information in a more readily understandable manner may be more effective at motivating behavior change. Strengths of this study include its cohort design and its robust data capture methods using food photographs and accelerometry.

Quantitation of hydrogen peroxide fluctuations and their modulation of dopamine dynamics in the rat dorsal striatum using fast-scan cyclic voltammetry.

The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson's disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson's disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum attenuated electrically evoked DA release, and also decreased basal DA levels in this brain region. These novel results will help to disambiguate the chemical mechanisms underlying the progression of neurodegenerative disease states, such as Parkinson's disease, that involve oxidative stress.

Chronically Implanted, Nafion-Coated Ag/AgCl Reference Electrodes for Neurochemical Applications.

Fast-scan cyclic voltammetry (FSCV) at carbon fiber microelectrodes can be used to measure behaviorally correlated dopamine changes in the extracellular fluid of the brain of freely moving rats. These experiments employ a chronically implanted Ag/AgCl reference electrode. When dopamine measurements are taken 4 days after implantation, there is often a potential shift, typically greater than +0.2 V, in the anodic and cathodic peaks in the cyclic voltammogram for dopamine. In this work, we optimized a method to coat sintered Ag/AgCl reference electrodes with the perfluorinated polymer, Nafion, to prevent this shift. We find that we can stabilize reference electrodes for up to 28 days. Immunohistochemistry of the tissue around the implant site shows extensive glial encapsulation around both bare and Nafion-coated devices. However, the lesion around bare electrodes has a rough texture implying that these cells are strongly adsorbed onto the bare reference electrode, while the lesion around a Nafion-coated electrode shows that cells are more intact implying that they adsorb less strongly. EDS and SEM analysis of the surface of the electrodes confirms this by visualizing a heavy build up of plaques, organic in nature, only on bare electrodes. Impedance spectroscopy indicates no difference between the impedance of bare and Nafion-coated Ag/AgCl electrodes, indicating that glial encapsulation does not lead to an increase in uncompensated resistance between the working and reference electrodes. The electrochemical shift therefore must be due to the unique chemical microenvironment around the reference electrode that alters the chloride equilibrium, a process that the Nafion coating prevents.