Faculty Bibliography

[This corrects the article DOI: 10.3389/fnins.2019.00117.].

Objective: To explore the applicability of an ambulatory inertial sensor (G-walk) to characterize gait function during the Timed Up and Go (TUG) Test under three different conditions.
Background(s): In Parkinson's disease (PD), the current lack of both reliable and feasible biomarkers of gait function and mobility limits the objective characterization of motor ability, clinical progression, and responsiveness to treatments. Current assessments of motor function rely on a clinicians' subjective judgement and/or the patient's self-reported questionnaires, which are not sensitive in capturing subtle changes over time and restrict comparability across raters. Ambulatory inertial sensors allow for non-invasive, wireless transmission of accurate quantitative data and therefore, may represent a useful tool in ambulatory settings. Design/Methods: Nineteen (19) PD patients (H&Y <4) and 10 agematched controls (CTRL) were consecutively enrolled to undergo inertial TUG (iTUG) testing under three experimental conditions: normal walking (iTUGnorm), dual task walking (iTUGcog), and at maximum speed (iTUGfast). The time needed to complete each test was sub-divided into six distinct phases quantified by the sensor: sitto- stand (1), forward gait (2), mid-turn (3), return gait (4), end-turn (5) and stand-to-sit (6). Other assessments included UDPRS Part III, MoCA, depression, fatigue, Benton and Rey-Osterrieth visual tests.
Result(s): A total of nineteen PD patients and ten CTRLs completed all assessments. PD patients were divided into mild (H&Y=2, n=12) and moderate (H&Y=3, n=7) disease severity. One-way-ANOVA and correlation analysis were performed. Different patterns of kinematic performance were observed (figure 1.A and 1.B). In PD, iTUG correlations were found with cognitive function, visual performance and motor severity, while in CTRLs there was only a correlation with motor performance only. iTUGfast performance seemed more sensitive experimental condition when PD was stratify by severity (figure 1.B).
Conclusion(s): iTUG assessed by an ambulatory inertial sensor is a quick, sensitive and feasible tool for objective measurements of functional mobility in PD. Utilizing validate tests for mobility and gait under different stress conditions can provide distinct information of gait function and mobility. Future longitudinal studies are warranted to better characterize the sensitivity to disease progression and the potential for monitoring and optimizing therapeutic interventions in this patient population. (Figure Presented)

Background: In ED patients who present with acute drug overdose, severe QTc prolongation (>500 ms) has been shown to be a predictor of adverse cardiovascular events (ACVE). However, it is unclear what clinical factors are associated with delayed severe QTc prolongation (dsQTp), and it is unknown whether dsQTp can predict ACVE. This study aims to: (1) Define clinical factors associated with dsQTp, and (2) test whether dsQTp is an independent predictor for ACVE.
Method(s): This was a prospective cohort study at 2 urban tertiary care EDs. Data was collected by trained research assistants, and included demographics, drug exposure, medication administration, initial and repeat ECG data, lab data, and outcome measures. dsQTp was defined as presence of initial QTc 499. The primary study outcome was the composite of ACVE defined as in-hospital occurrence of any of the following: MI, shock, ventricular dysrhythmia, and cardiac arrest. Univariate statistics and multivariable logistic regression calculations were made using SPSS version 24. With a fixed sample size of 1670, we calculated that we would have 99% power to show a 3-fold increase in risk with 0.05 alpha.
Result(s): Out of 2311 patients screened, 641 were excluded (age 500) leaving 1670 patients for analysis. The dsQTp group (N = 27) was found to be older than the control group (N = 1643)(40.1 vs 51.6, P
Conclusion(s): This cohort study reveals a subset of ED patients who are at greater risk of overdose-related ACVE but not immediately apparent by the initial ECG. Further study is needed to identify which patients are at risk for dsQTp, as they may require prolonged observation and repeated ECGs. Limitations include missing repeat QTc measurements, and inability to control for overdose severity as a surrogate for repeat ECGs. Future study is warranted to further characterize patients at risk for dsQTp to evaluate other exposure-related factors as yet undiscovered

Learning, memory, and emotional regulation are all modulated by sleep. Sleep influences on neural circuit function and plasticity occur in all mammalian brain regions examined to date, including the noncanonical olfactory system, suggesting sleep disruption could have wide-ranging consequences on behavior and cognition. New evidence suggests that sleep disturbances during early development can have particularly insidious and long-lasting consequences. In particular, work from our lab and others suggests that early-life adverse events can disrupt sleep across the life span, thus contributing to a variety of negative cognitive and behavioral outcomes. These findings raise the possibility that interventions targeting sleep may have therapeutic value for children or adults exposed to early-life adverse events. Here, we describe sleep and sleep ontogeny and then describe the role of sleep in normal and pathological brain function. Finally, we explore how early-life adverse events and sleep disturbances may reciprocally interact to produce a range of psychopathological outcomes.
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The dentate gyrus (DG) and its primary cell type, the granule cell (GC), are thought to be critical to many cognitive functions. A major neuronal subtype of the DG is the hilar mossy cell (MC). MCs have been considered to play an important role in cognition, but in vivo studies to understand the activity of MCs during cognitive tasks are challenging because the experiments usually involve trauma to the overlying hippocampus or DG, which kills hilar neurons. In addition, restraint typically occurs, and MC activity is reduced by brief restraint stress. Social isolation often occurs and is potentially confounding. Therefore, we used c-fos protein expression to understand when MCs are active in vivo in socially housed adult C57BL/6 mice in their home cage. We focused on c-fos protein expression after animals explored novel objects, based on previous work which showed that MCs express c-fos protein readily in response to a novel housing location. Also, MCs are required for the training component of the novel object location task and novelty-encoding during a food-related task. GluR2/3 was used as a marker of MCs. The results showed that MC c-fos protein is greatly increased after exposure to novel objects, especially in ventral DG. We also found that novel objects produced higher c-fos levels than familiar objects. Interestingly, a small subset of neurons that did not express GluR2/3 also increased c-fos protein after novel object exposure. In contrast, GCs appeared relatively insensitive. The results support a growing appreciation of the role of the DG in novelty detection and novel object recognition, where hilar neurons and especially MCs are very sensitive.