Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.

Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1+) cells are a major source of activated fibroblasts in multiple organs, but the links between injury, inflammation, and Gli1+ cell expansion and tissue fibrosis remain incompletely understood. We demonstrated that leukocyte-derived tumor necrosis factor (TNF) promoted Gli1+ cell proliferation and cardiorenal fibrosis through induction and release of Indian Hedgehog (IHH) from renal epithelial cells. Using single-cell-resolution transcriptomic analysis, we identified an "inflammatory" proximal tubular epithelial (iPT) population contributing to TNF- and nuclear factor κB (NF-κB)-induced IHH production in vivo. TNF-induced Ubiquitin D (Ubd) expression was observed in human proximal tubular cells in vitro and during murine and human renal disease and aging. Studies using pharmacological and conditional genetic ablation of TNF-induced IHH signaling revealed that IHH activated canonical Hedgehog signaling in Gli1+ cells, which led to their activation, proliferation, and fibrosis within the injured and aging kidney and heart. These changes were inhibited in mice by Ihh deletion in Pax8-expressing cells or by pharmacological blockade of TNF, NF-κB, or Gli1 signaling. Increased amounts of circulating IHH were associated with loss of renal function and higher rates of cardiovascular disease in patients with chronic kidney disease. Thus, IHH connects leukocyte activation to Gli1+ cell expansion and represents a potential target for therapies to inhibit inflammation-induced fibrosis.

Evaluation of a longitudinal pharmacogenomics education on pharmacist knowledge in a multicampus healthcare system.

Aim: To evaluate the effect of pharmacogenomics (PGx) education for pharmacists. Materials & Methods: Three-part weekly webinar series occurred in 2021. Pharmacists were assessed on their PGx knowledge at baseline and after each webinar. The primary end point was a change in the percent of correct responses between the baseline and week 1 assessment. Secondary end points included change in knowledge at weeks 4-8 and change in self-efficacy. Results: In total, 19 of 58 participants were eligible for the primary analysis, which showed an average improvement of 37% (p < 0.0001). Knowledge remained consistent between week 1 and weeks 4-8. Average self-efficacy increased (p < 0.0001) and was maintained at weeks 4-8. Conclusion: The PGx webinar series resulted in a lasting improvement in PGx knowledge and self-efficacy.

Head movements and simulator sickness generated by a virtual environment.

BACKGROUND: For virtual environments (VEs) to be useful in training it is important to understand the negative effects of VE exposure. The purpose of this study was to observe head movements in virtual and real environments and the relation between those movements and simulator sickness. METHOD: There were 48 men who were trained in 4-person teams in either a head-mounted display (HMD)-based VE or in a real world environment. Head position data were collected in both systems and simulator sickness scores were collected in the VE. The relationship of head movements and sickness scores in theVE was examined and the degree of head movements in the real world and VE compared. RESULTS: Differences were found in the length of time subjects spent moving their heads; subjects with the highest sickness scores moved their heads less often than other subjects in the VE. Also, subjects moved their heads significantly less and less often in the VE (means: 3 degrees x 50 ms(-1), 71% of trial time not moving head), compared to the real world (means: 10 degrees 50 ms(-1), 59% of trial time not moving head). CONCLUSIONS: This study observed that when head movements are quantified, past assumptions of the link between increased sickness scores and decreased head movements may not hold. Though not linked to simulator sickness, head movements were reduced in the VE compared to the real world. Though observational in nature, this study is one of the first to quantify head movements and how they may relate to simulator sickness.

Choosing between an apple and a chocolate bar: the impact of health and taste labels.

Increasing the consumption of fruit and vegetables is a central component of improving population health. Reasons people give for choosing one food over another suggest health is of lower importance than taste. This study assesses the impact of using a simple descriptive label to highlight the taste as opposed to the health value of fruit on the likelihood of its selection. Participants (N=439) were randomly allocated to one of five groups that varied in the label added to an apple: apple; healthy apple; succulent apple; healthy and succulent apple; succulent and healthy apple. The primary outcome measure was selection of either an apple or a chocolate bar as a dessert. Measures of the perceived qualities of the apple (taste, health, value, quality, satiety) and of participant characteristics (restraint, belief that tasty foods are unhealthy, BMI) were also taken. When compared with apple selection without any descriptor (50%), the labels combining both health and taste descriptors significantly increased selection of the apple ('healthy & succulent' 65.9% and 'succulent & healthy' 62.4%), while the use of a single descriptor had no impact on the rate of apple selection ('healthy' 50.5% and 'succulent' 52%). The strongest predictors of individual dessert choice were the taste score given to the apple, and the lack of belief that healthy foods are not tasty. Interventions that emphasize the taste attributes of healthier foods are likely to be more effective at achieving healthier diets than those emphasizing health alone.

Respiratory sinus arrhythmia as a measure of cognitive workload.

The current standard for measuring cognitive workload is the NASA Task-load Index (TLX) questionnaire. Although this measure has a high degree of reliability, diagnosticity, and sensitivity, a reliable physiological measure of cognitive workload could provide a non-invasive, objective measure of workload that could be tracked in real or near real-time without interrupting the task. This study investigated changes in respiratory sinus arrhythmia (RSA) during seven different sub-sections of a proposed selection test for Navy aviation and compared them to changes reported on the NASA-TLX. 201 healthy participants performed the seven tasks of the Navy's Performance Based Measure. RSA was measured during each task and the NASA-TLX was administered after each task. Multi-level modeling revealed that RSA significantly predicted NASA-TLX scores. A moderate within-subject correlation was also found between RSA and NASA TLX scores. The findings support the potential development of RSA as a real-time measure of cognitive workload.

The effects of 28 hours of sleep deprivation on respiratory sinus arrhythmia during tasks with low and high controlled attention demands.

Task performance while sleep deprived may be moderated by the controlled attention required by the task (Pilcher, Band, Odle-Dusseau, & Muth, 2007). This study examined the effects of 28 h of sleep deprivation on respiratory sinus arrhythmia (RSA) during tasks with low and high controlled attention demands. The results showed that RSA increased throughout the night for both task types, but was consistently reduced during the low compared to high controlled attention tasks. The increase in RSA was linear for the high controlled attention tasks but curvilinear for the low ones. Hence, RSA followed a circadian pattern during the low controlled attention tasks but not the high ones. These results suggest that the effects of sleep deprivation on task performance may be moderated by parasympathetic activity and task type, and this has implications for task assignment during sustained operations that cause sleep deprivation.

Physiological compliance and team performance.

Physiological compliance (PC) refers to the correlation between physiological measures of team members over time. The goals of this study were to examine ways of measuring PC in heart rate variability (HRV) data and the relationship between PC and team performance. Teams were tasked with entering both real and simulated rooms and "shooting" individuals with a weapon and identifying individuals without a weapon. The linear correlation and directional agreement PC methods were shown to be the most sensitive to differences in performance, with greater PC being associated with better performance. The correlation method when applied to a measure of respiratory sinus arrhythmia (RSA) revealed a significant difference between high and low performers (t[8]=-2.31, p=0.03) and the directional agreement applied to inter-beat-intervals and RSA revealed trend-level differences (t[4.62]=-1.86, p=0.06 and t[8]=-1.68, p=0.07). These results suggest that PC may have merit for predicting team performance.

Effects of uncoupled motion on performance.

OBJECTIVES: To determine whether human exposure to vehicle motion specifically affects performance on a similar, yet uncorrelated, driving task and to observe the motion/simulator sickness symptoms that were associated with the real vehicle motion and the driving task. BACKGROUND: Past research has shown uncoupled motion can affect a person's performance on a task as well as induce motion sickness. METHODS: Ten participants (age range = 19-25 years) completed an uncorrelated driving task while seated in a stationary real vehicle and a moving real vehicle. RESULTS: The results show participants took longer to complete the motion condition, t(9) = 1.96, p < .05, and were less accurate, t(9) = 3.73, p < .05. Scores for the Motion Sickness Assessment Questionnaire, t(9) = 3.37, p < .05, and the Simulator Sickness Questionnaire, t(9) = 3.30, p < .05, were significantly higher during the motion condition. CONCLUSIONS: Performance on the task was degraded and motion sickness heightened during the motion condition. APPLICATION: This research has potential implications for military-related tasks such as operating a command and control station or controlling a remote vehicle while simultaneously being a passenger in a real vehicle, as well as for civilian applications such as interacting with a moving map navigation system while driving a car.