Real-Life Turning Movements Capture Subtle Longitudinal and Preataxic Changes in Cerebellar Ataxia.

BACKGROUND: Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints that capture change in ataxia severity in patients' real life. OBJECTIVES: This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real-life turning movements that are sensitive for changes both longitudinally and at the preataxic stage. METHODS: Combined cross-sectional (n = 30) and longitudinal (n = 14, 1-year interval) observational study in degenerative cerebellar disease (including eight preataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body-worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real-life movements. RESULTS: Measures that quantified dynamic balance during turning-lateral velocity change (LVC) and outward acceleration-but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life (effect size δ = 0.68), with LVC also differentiating preataxic against healthy subjects (δ = 0.53). LVC was highly correlated with clinical ataxia severity (scale for the assessment and rating of ataxia [SARA] score, effect size ρ = 0.79) and patient reported balance confidence (activity-specific balance confidence scale [ABC] score, ρ = 0.66). Moreover, LVC in real life-but not general turning measures or the SARA score-allowed detecting significant longitudinal change in 1-year follow-up with high effect size (rprb  = 0.66). CONCLUSIONS: Measures of turning allow capturing specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers, even in the highly treatment-relevant early stages of degenerative cerebellar disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

An immersive first-person navigation task for abstract knowledge acquisition.

Advances in virtual reality (VR) technology have greatly benefited spatial navigation research. By presenting space in a controlled manner, changing aspects of the environment one at a time or manipulating the gain from different sensory inputs, the mechanisms underlying spatial behaviour can be investigated. In parallel, a growing body of evidence suggests that the processes involved in spatial navigation extend to non-spatial domains. Here, we leverage VR technology advances to test whether participants can navigate abstract knowledge. We designed a two-dimensional quantity space-presented using a head-mounted display-to test if participants can navigate abstract knowledge using a first-person perspective navigation paradigm. To investigate the effect of physical movement, we divided participants into two groups: one walking and rotating on a motion platform, the other group using a gamepad to move through the abstract space. We found that both groups learned to navigate using a first-person perspective and formed accurate representations of the abstract space. Interestingly, navigation in the quantity space resembled behavioural patterns observed in navigation studies using environments with natural visuospatial cues. Notably, both groups demonstrated similar patterns of learning. Taken together, these results imply that both self-movement and remote exploration can be used to learn the relational mapping between abstract stimuli.

The anorexigenic effect of neuropeptide K in chicks involves the paraventricular nucleus and arcuate nucleus of the hypothalamus.

Neuropeptide K (NPK) induces satiety in birds and mammals. We demonstrated that in birds this effect was associated with the hypothalamus, but beyond this little is known in any species regarding the central mechanism of action. Thus, this study was designed to identify hypothalamic molecular mechanisms associated with the food intake-inhibiting effects of NPK in chicks. In Experiment 1, intracerebroventricular (ICV) injection of 1.0 and 3.0 nmol of NPK reduced food intake and we identified an effective dose for microinjection. In Experiment 2, food intake was reduced when NPK was microinjected into the PVN. In Experiment 3, whole hypothalamus was collected from chicks at 1 h post-ICV NPK injection. The abundance of corticotropin-releasing factor (CRF) and agouti-related peptide (AgRP) mRNA was reduced in NPK-injected chicks. In Experiment 4, within the isolated paraventricular nucleus (PVN) there was less CRF mRNA, and within the arcuate nucleus (ARC) there was less AgRP mRNA, in NPK- than vehicle-treated chicks at 1 h post-injection. We conclude that there are first order neurons for NPK that reside within the PVN, and the anorexigenic effect of NPK is associated with a decrease in AgRP in the ARC.

Incorporation of lean methodology into pharmacy residency programs.

PURPOSE: The implementation of lean methodology into pharmacy residency programs at a community teaching hospital is described. SUMMARY: New Hanover Regional Medical Center, a community teaching hospital in southeastern North Carolina, fully adopted a lean culture in 2010. Given the success of lean strategies organizationally, this methodology was used to assist with the evaluation and development of its pharmacy residency programs in 2014. Lean tools and activities have also been incorporated into residency requirements and rotation learning activities. The majority of lean events correspond to the required competency areas evaluating leadership and management, teaching, and education. These events have included participation in and facilitation of various lean problem-solving and communication tools. The application of the 4 rules of lean has resulted in enhanced management of the programs and provides a set of tools by which continual quality improvement can be ensured. Regular communication and direct involvement of all invested parties have been critical in developing and sustaining new improvements. In addition to program enhancements, lean methodology offers novel methods by which residents may be incorporated into leadership activities. CONCLUSION: The incorporation of lean methodology into pharmacy residency programs has translated into a variety of realized and potential benefits for the programs, the preceptors and residents, and the health system. Specific areas of growth have included quality-improvement processes, the expansion of leadership opportunities for residents, and improved communication among program directors, preceptors, and residents.

LPLRFamide exerts short-term anorexigenic effects that coincide with magnocellular division of the hypothalamic paraventricular nucleus activation.

LPLRFamide is a member of the RFamide peptide family that elicits an anorexigenic effect when centrally injected in chicks although the mechanism mediating this response is poorly understood. Therefore, the purpose of this experiment was to elucidate the hypothalamic mechanism of short-term anorexia after central administration of LPLRFamide in chicks. In Experiment 1 chicks centrally injected with LPLRFamide decreased food intake at 15min but not 30min following administration compared to vehicle-injected chicks. For Experiment 2, c-Fos immunoreactivity was quantified in several appetite-associated hypothalamic nuclei and in LPLRF-injected chicks, compared to vehicle-injected chicks, there was an increase in the number of reactive cells in the magnocellular division of the paraventricular nucleus. Lastly in Experiment 3, real time-PCR was performed and hypothalamic proopiomelanocortin (POMC) mRNA abundance was increased in LPRLFamide-injected chicks compared to vehicle-injected chicks. Thus, following central injection of LPLRFamide there is activation of the paraventricular nucleus of the hypothalamus and increased expression of hypothalamic POMC mRNA in chicks.