“I'm not telling an illness story. I'm telling a story of opportunity”: Making sense of voice hearing experiences

Background/aim: Traditional approaches to voice hearing discourage the exploration of this experience. Current evidence suggests that understanding voice hearing experiences (VHE) facilitates recovery; yet, little is known about how voice hearers make sense of this phenomenon. This study aimed to explore how adults with lived experiences of voice hearing understand their VHE. Method: A phenomenological approach guided the study design. In-depth, semi-structured interviews were conducted with five participants who attended the Hearing Voices Recovery Support Group in Sydney, Australia. Participants completed the Self- Identified Stages of Recovery questionnaire and the Revised Beliefs About Voices Questionnaire. Thematic analysis was employed to uncover the ‘essence’ of this phenomenon. Findings: Understanding the voice hearing experience was characterized by an overarching theme of ‘tension and recalibration’. This overarching theme permeated each of five sub-themes: beliefs about voices; navigating the relationship with my voices; learning to live with my voices; rediscovering myself with my voices; and, influences to understanding my voices. Conclusion: This study highlights how voice hearer’s understanding of VHE evolves over time, and throughout phases of recovery. Clinical implications include early intervention to support individuals to: explore their VHE to derive personal meaning; navigate their relationships with voices to promote mutually beneficial relationships; and, regain a positive sense of self

“I'm not telling an illness story. I'm telling a story of opportunity”: Making sense of voice hearing experiences

Background/aim: Traditional approaches to voice hearing discourage the exploration of this experience. Current evidence suggests that understanding voice hearing experiences (VHE) facilitates recovery; yet, little is known about how voice hearers make sense of this phenomenon. This study aimed to explore how adults with lived experiences of voice hearing understand their VHE. Method: A phenomenological approach guided the study design. In-depth, semi-structured interviews were conducted with five participants who attended the Hearing Voices Recovery Support Group in Sydney, Australia. Participants completed the Self- Identified Stages of Recovery questionnaire and the Revised Beliefs About Voices Questionnaire. Thematic analysis was employed to uncover the ‘essence’ of this phenomenon. Findings: Understanding the voice hearing experience was characterized by an overarching theme of ‘tension and recalibration’. This overarching theme permeated each of five sub-themes: beliefs about voices; navigating the relationship with my voices; learning to live with my voices; rediscovering myself with my voices; and, influences to understanding my voices. Conclusion: This study highlights how voice hearer’s understanding of VHE evolves over time, and throughout phases of recovery. Clinical implications include early intervention to support individuals to: explore their VHE to derive personal meaning; navigate their relationships with voices to promote mutually beneficial relationships; and, regain a positive sense of self

Diverse roles for VEGF-A in the nervous system

Vascular endothelial growth factor A (VEGF-A) is best known for its essential roles in blood vessel growth. However, evidence has emerged that VEGF-A also promotes a wide range of neuronal functions, both in vitro and in vivo, including neurogenesis, neuronal migration, neuronal survival and axon guidance. Recent studies have employed mouse models to distinguish the direct effects of VEGF on neurons from its indirect, vessel-mediated effects. Ultimately, refining our knowledge of VEGF signalling pathways in neurons should help us to understand how the current use of therapeutics targeting the VEGF pathway in cancer and eye disease might be expanded to promote neuronal health and nerve repair

Neural crest cell-derived VEGF promotes embryonic jaw extension

Jaw morphogenesis depends on the growth of Meckel’s cartilage during embryogenesis. However, the cell types and signals that promote chondrocyte proliferation for Meckel’s cartilage growth are poorly defined. Here we show that neural crest cells (NCCs) and their derivatives provide an essential source of the vascular endothelial growth factor (VEGF) to enhance jaw vascularization and stabilize the major mandibular artery. We further show in two independent mouse models that blood vessels promote Meckel’s cartilage extension. Coculture experiments of arterial tissue with NCCs or chondrocytes demonstrated that NCC-derived VEGF promotes blood vessel growth and that blood vessels secrete factors to instruct chondrocyte proliferation. Computed tomography and X-ray scans of patients with hemifacial microsomia also showed that jaw hypoplasia correlates with mandibular artery dysgenesis. We conclude that cranial NCCs and their derivatives provide an essential source of VEGF to support blood vessel growth in the developing jaw, which in turn is essential for normal chondrocyte proliferation, and therefore jaw extension

Dysfunctional mechanotransduction through the YAP/TAZ/Hippo pathway as a feature of chronic disease

In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions

Axonal and neuromuscular synaptic phenotypes in Wld(S), SOD1(G93A) and ostes mutant mice identified by fiber-optic confocal microendoscopy

We used live imaging by fiber-optic confocal microendoscopy (CME) of yellow fluorescent protein (YFP) expression in motor neurons to observe and monitor axonal and neuromuscular synaptic phenotypes in mutant mice. First, we visualized slow degeneration of axons and motor nerve terminals at neuromuscular junctions following sciatic nerve injury in WldS mice with slow Wallerian degeneration. Protection of axotomized motor nerve terminals was much weaker in WldS heterozygotes than in homozygotes. We then induced covert modifiers of axonal and synaptic degeneration in heterozygous WldS mice, by N-ethyl-Nnitrosourea (ENU) mutagenesis, and used CME to identify candidate mutants that either enhanced or suppressed axonal or synaptic degeneration. From 219 of the F1 progeny of ENU-mutagenized BALB/c mice and thy1.2-YFP16/WldS mice, CME revealed six phenodeviants with suppression of synaptic degeneration. Inheritance of synaptic protection was confirmed in three of these founders, with evidence of Mendelian inheritance of a dominant mutation in one of them (designated CEMOP_S5). We next applied CME repeatedly to living WldS mice and to SOD1G93A mice, an animal model of motor neuron disease, and observed degeneration of identified neuromuscular synapses over a 1–4 day period in both of these mutant lines. Finally, we used CME to observe slow axonal regeneration in the ENU-mutant ostes mouse strain. The data show that CME can be used to monitor covert axonal and neuromuscular synaptic pathology and, when combined with mutagenesis, to identify genetic modifiers of its progression in vivo

Mechanosensing and the Hippo pathway in microglia : a potential link to Alzheimer’s disease pathogenesis

The activation of microglia, the inflammatory cells of the central nervous system (CNS), has been linked to the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases. How microglia sense the changing brain environment, in order to respond appropriately, is still being elucidated. Microglia are able to sense and respond to the mechanical properties of their microenvironment, and the physical and molecular pathways underlying this mechanosensing/mechanotransduction in microglia have recently been investigated. The Hippo pathway functions through mechanosensing and subsequent protein kinase cascades, and is critical for neuronal development and many other cellular processes. In this review, we examine evidence for the potential involvement of Hippo pathway components specifically in microglia in the pathogenesis of Alzheimer’s disease. We suggest that the Hippo pathway is worth investigating as a mechanosensing pathway in microglia, and could be one potential therapeutic target pathway for preventing microglial-induced neurodegeneration in A

Fitts’ Law: On Calculating Throughput and Non-ISO Tasks

We used a target-selection task to evaluate head-tracking as an input method for mobile devices. First, the method of calculating Fitts’ throughput is described by means of a raw data detailed example. Then, the method of calculating throughput is discussed for non-ISO tasks, since the procedure targets were randomly positioned from trial to trial. Due to a non-constant amplitude within each sequence of trials, throughput was calculated using two methods of data aggregation: the first one, by sequence of trials using the mean amplitude, and the second one, by common A-W conditions. For each data set, we used four methods for calculating throughput. The grand mean for throughput (calculated through the division of means and the adjustment for accuracy) was of 0.74 bps, which is 45 % lower than the value obtained using an ISO task. We recommend to calculate throughput using the division of means plus the adjustment for accuracy, and to avoid using the reciprocal slope of the regression model. We present various design recommendations for non-ISO tasks, such as: i) to keep amplitude and constant target within each sequence of trials, and ii) to use strategies to avoid or remove reaction time

Macrophage-induced blood vessels guide Schwann cell-mediated regeneration of peripheral nerves

The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue