Is Freezing of Gait in Parkinson's Disease a Result of Multiple Gait Impairments? Implications for Treatment

Several gait impairments have been associated with freezing of gait (FOG) in patients with Parkinson's disease (PD). These include deteriorations in rhythm control, gait symmetry, bilateral coordination of gait, dynamic postural control and step scaling. We suggest that these seemingly independent gait features may have mutual interactions which, during certain circumstances, jointly drive the predisposed locomotion system into a FOG episode. This new theoretical framework is illustrated by the evaluation of the potential relationships between the so-called “sequence effect”, that is, impairments in step scaling, and gait asymmetry just prior to FOG. We further discuss what factors influence gait control to maintain functional gait. “Triggers”, for example, such as attention shifts or trajectory transitions, may precede FOG. We propose distinct categories of interventions and describe examples of existing work that support this idea: (a) interventions which aim to maintain a good level of locomotion control especially with respect to aspects related to FOG; (b) those that aim at avoiding FOG “triggers”; and (c) those that merely aim to escape from FOG once it occurs. The proposed theoretical framework sets the stage for testable hypotheses regarding the mechanisms that lead to FOG and may also lead to new treatment ideas

Evidence for a relationship between bilateral coordination during complex gait tasks and freezing of gait in Parkinson\u27s disease

BACKGROUND: Freezing of gait is a debilitating and common gait disturbance observed in individuals with Parkinson’s disease (PD). Although the underlying mechanisms of freezing remain unclear, bilateral coordination of steps, measured as a phase coordination index, has been suggested to be related to freezing. Phase coordination index has not, however, been measured during tasks associated with freezing such as turning and backward walking. Understanding how bilateral coordination changes during tasks associated with freezing may improve our understanding of the causes of freezing. METHODS: Twelve individuals with PD who freeze (freezers), 19 individuals with PD who do not freeze (non-freezers), and 10 healthy, age-matched older adults participated. General motor disease severity and freezing severity were assessed. Phase coordination index was calculated for all subjects during forward walking, backward walking, continuous turning in small radius circles, and turning in large radius circles. RESULTS: Freezers and non-freezers had similar disease duration and general motor severity. Stepping coordination (measured as phase coordination index) was significantly worse in freezers compared to non-freezers and controls. Turning and backward walking, tasks related to freezing, resulted in worse coordination with respect to forward walking. Coordination was associated with severity of freezing scores such that worse coordination was correlated with more severe freezing. CONCLUSIONS: These results provide evidence that stepping coordination is related to freezing in people with PD. Identifying variables associated with freezing may provide insights into factors underlying this symptom, and may inform rehabilitative interventions to reduce its occurrence in PD

Probing topological invariants in the bulk of a non-Hermitian optical system

Topological insulators are insulating in the bulk but feature conducting states on their surfaces. Standard methods for probing their topological properties largely involve probing the surface, even though topological invariants are defined via the bulk band structure. Here, we utilize non-hermiticy to experimentally demonstrate a topological transition in an optical system, using bulk behavior only, without recourse to surface properties. This concept is relevant for a wide range of systems beyond optics, where the surface physics is difficult to probe

Experimental realization of a topological Anderson insulator

We experimentally demonstrate that disorder can induce a topologically non-trivial phase. We implement this “Topological Anderson Insulator” in arrays of evanescently coupled waveguides and demonstrate its unique features

Toll-like receptor 4 signaling activates ERG function in prostate cancer and provides a therapeutic target

The TMPRSS2-ERG gene fusion and subsequent overexpression of the ERG transcription factor occurs in ∼50% of prostate tumors, making it the most common abnormality of the prostate cancer genome. While ERG has been shown to drive tumor progression and cancer-related phenotypes, as a transcription factor it is difficult to target therapeutically. Using a genetic screen, we identified the toll-like receptor 4 (TLR4) signaling pathway as important for ERG function in prostate cells. Our data confirm previous reports that ERG can transcriptionally activate TLR4 gene expression; however, using a constitutively active ERG mutant, we demonstrate that the critical function of TLR4 signaling is upstream, promoting ERG phosphorylation at serine 96 and ERG transcriptional activation. The TLR4 inhibitor, TAK-242, attenuated ERG-mediated migration, clonogenic survival, target gene activation and tumor growth. Together these data indicate a mechanistic basis for inhibition of TLR4 signaling as a treatment for ERG-positive prostate cancer

Acknowledging the Relevance of Elephant Sensory Perception to Human–Elephant Conflict Mitigation

Elephants are well known for their socio-cognitive abilities and capacity for multi-modal sensory perception and communication. Their highly developed olfactory and acoustic senses provide them with a unique non-visual perspective of their physical and social worlds. The use of these complex sensory signals is important not only for communication between conspecifics, but also for decisions about foraging and navigation. These decisions have grown increasingly risky given the exponential increase in unpredictable anthropogenic change in elephants’ natural habitats. Risk taking often develops from the overlap of human and elephant habitat in Asian and African range countries, where elephants forage for food in human habitat and crop fields, leading to conflict over high-quality resources. To mitigate this conflict, a better understanding of the elephants’ sensory world and its impact on their decision-making process should be considered seriously in the development of long-term strategies for promoting coexistence between humans and elephants. In this review, we explore the elephants’ sensory systems for audition and olfaction, their multi-modal capacities for communication, and the anthropogenic changes that are affecting their behavior, as well as the need for greater consideration of elephant behavior in elephant conservation efforts