Visuo-tactile stimulation, but not type of movement, modulates pain during the vision of a moving virtual limb

Aims: Evidence has revealed a relationship between pain and the observation of limb movement, but it is unknown whether different types of movements have diverse modulating effects. In this immersive virtual reality study we explored the effect of the vision of different virtual arm movements (arm vs. wrist) on pain threshold from heat applied to the wrist. Patients & Methods: Forty healthy participants underwent four conditions in virtual reality while heat pain thresholds were measured. Visuo-tactile stimulation was used to attempt to modulate the feeling of virtual limb ownership. Results: Effects on pain threshold were present for type of stimulation but not type of movement. Conclusions: The type of observed movement does not appear to influence pain modulation, at least not during acute pain states

Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies

PURPOSE: To investigate and describe in detail the demographics, functional and anatomic characteristics, and clinical course of Leber congenital amaurosis (LCA) associated with mutations in the CEP290 gene (LCA-CEP290) in a large cohort of adults and children. DESIGN: Retrospective case series. PARTICIPANTS: Patients with mutations in CEP290 identified at a single UK referral center. METHODS: Review of case notes and results of retinal imaging (color fundus photography, fundus autofluorescence [FAF] imaging, OCT), electrophysiologic assessment, and molecular genetic testing. MAIN OUTCOME MEASURES: Molecular genetic testing, clinical findings including visual acuity and retinal imaging, and electrophysiologic assessment. RESULTS: Forty patients with LCA-CEP290 were identified. The deep intronic mutation c.2991+1655 A>G was the most common disease-causing variant (23/40 patients) identified in the compound heterozygous state in 20 patients (50%) and homozygous in 2 patients (5%). Visual acuity (VA) varied from 6/9 to no perception of light, and only 2 of 12 patients with longitudinal VA data showed deterioration in VA in their better-seeing eye over time. A normal fundus was found at diagnosis in younger patients (mean age, 1.9 years), with older patients showing white flecks (mean age, 5.9 years) or pigmentary retinopathy (mean age, 21.7 years). Eleven of 12 patients (92%) with OCT imaging had preservation of foveal architecture. Ten of 12 patients (83%) with FAF imaging had a perifoveal hyperautofluorescent ring. Having 2 nonsense CEP290 mutations was associated with worse final VA and the presence of nonocular features. CONCLUSIONS: Detailed analysis of the clinical phenotype of LCA-CEP290 in a large cohort confirms that there is a window of opportunity in childhood for therapeutic intervention based on relative structural preservation in the central cone-rich retina in a significant proportion of patients, with the majority harboring the deep intronic variant potentially tractable to several planned gene editing approaches

Pharmaceutical pollution of the world's rivers

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals

MAXIMAL VO2 AT EXTREME ENDS OF THE DAY FOLLOWING GLUCOSE PROVISION

Jenna L. Carducci1, Matthew J. Garver1, Whitley J. Stone1, Meera Penumetcha1, Dustin W. Davis1, Adam R. McMillin1, Josie N. Hair1, Nicolas M. Philipp1, Jordan R. Elledge1, Emily B. Sheck1, & Katherine M. Scherry1 1University of Central Missouri, Warrensburg, Missouri Exercise programs are more favorable when individualized to particular needs and preferences. Controlling training and exercise characteristics such as time of day and glucose provision may enhance subsequent performance. PURPOSE: The purpose of this research was to investigate maximal VO2 at extreme ends of the day following a standardized glucose provision. METHODS: Thirteen participants (Females: 8, Males: 5, Age: 20.7 ± 1.4 yrs., BMI: 24.9 ± 3.0 kg/m2) volunteered to complete two maximal VO2 tests, one between 06:00-09:00 and the other between 21:00-24:00. A familiarization trial was utilized to mitigate a learning effect and determine the speed that elicited a perceived effort of 12-13 on the Borg 6-20 RPE scale when steady-stated. Considering body mass and activity level, a standardized test meal of approximately 80% carbohydrates, 3% fat, and 17% protein was provided 2 hours prior to testing. For the maximal testing, treadmill speed was maintained at the predetermined intensity, and grade was increased 2% every 2 minutes until volitional fatigue. Maximal VO2 was determined via a metabolic cart using a 15-breath moving average. RESULTS: The maximal tests lasted 10.13 ± 2.15 minutes. There was no statistical difference (p \u3c .05) found for morning vs. evening tests for maximal VO2 (47.0 ± 7.0 vs. 47.3 ± 8.0 ml/kg/min). CONCLUSION: The glucose provision prior to exercise was intended to standardize nutrient intake prior to completing the maximal VO2 tests. The results of this study align with the available literature suggesting that maximal VO2 does not significantly differ between morning and evening exercise tests. Exercising at extreme ends of the day may not result in a significant difference in maximal VO2 among a group of younger, recreationally active adults provided a high-glucose test meal. ACKNOWLEDGEMENTS: This research was funded by the Graduate Student Research Fund from the University of Central Missouri

MAXIMAL PERCEIVED EFFORT DURING MAXIMAL RUNNING AT EXTREME ENDS OF THE DAY

Nicolas M. Philipp1, Jenna L. Carducci1, Matthew J. Garver1, Whitley J. Stone1, Meera Penumetcha1, Dustin W. Davis1, Adam R. McMillin1, Josie N. Hair1, Jordan R. Elledge1, Emily B. Sheck1, & Katherine M. Scherry1 1University of Central Missouri, Warrensburg, Missouri Borg’s RPE Scale is commonly used to measure perceived exertion during exercise. Imposed exercise times, such as early morning or late evening, may impact perceived exertion. PURPOSE: Perceived exertion was recorded during maximal treadmill running to determine if there was a significant difference between extreme ends of the day. METHODS: Thirteen (Females: 8, Males: 5) recreationally trained individuals (Age: 20.7 ± 1.4 yrs.) underwent maximal testing on two occasions—a morning session (6:00-9:00) and an evening session (21:00-24:00). Prior to maximal testing, participants completed a familiarization trial purposed to limit learning effect and establish an individualized, comfortable jogging speed eliciting a steady-state RPE of 12-13 on the 6-20 Borg scale. Participants were provided a standardized meal (high CHO smoothie based on body weight and activity level) to be consumed 2h before testing. During maximal testing, participants maintained the constant jogging speed at the intensity determined during familiarization. Every 2 minutes, grade increased by 2% until volitional exhaustion. The RPE was recorded near the completion of each stage and immediately after termination of the test. RESULTS: The mean maximal test duration was 10.13 ± 2.15 minutes. A paired samples t-test indicated that maximal RPE did not differ (p = .25) between morning (18.9 ± 1.1) and evening (18.8 ± 1.5) tests. A paired samples t-test between session 1 and session 2 revealed an order effect (18.5 vs. 19.1, p = .047), with session 2 being perceived as exertionally more demanding. CONCLUSION: No difference was found in maximal RPE between the tests performed at 6:00-9:00 and 21:00-24:00. Interestingly, session 2 was perceived as more exertionally demanding when compared to session 1. These data support that there is no difference in maximal RPE when exercising at extreme ends of the day; however, recreationally trained individuals may perceive a maximal exercise test as more difficult if repeated within 36-72h. ACKNOWLEDGEMENTS: This research was funded by the Graduate Student Research Fund from the University of Central Missouri