Within- and between-session prefrontal cortex response to virtual reality exposure therapy for acrophobia

Exposure Therapy (ET) has demonstrated its efficacy in the treatment of phobias, anxiety and Post-traumatic Stress Disorder (PTSD), however, it suffers a high drop-out rate because of too low or too high patient engagement in treatment. Virtual Reality Exposure Therapy (VRET) is comparably effective regarding symptom reduction and offers an alternative tool to facilitate engagement for avoidant participants. Neuroimaging studies have demonstrated that both ET and VRET normalize brain activity within a fear circuit. However, previous studies have employed brain imaging technology which restricts people’s movement and hides their body, surroundings and therapist from view. This is at odds with the way engagement is typically controlled. We used a novel combination of neural imaging and VR technology—Functional Near-Infrared Spectroscopy (fNIRS) and Immersive Projection Technology (IPT), to avoid these limitations. Although there are a few studies that have investigated the effect of VRET on a brain function after the treatment, the present study utilized technologies which promote ecological validity to measure brain changes after VRET treatment. Furthermore, there are no studies that have measured brain activity within VRET session. In this study brain activity within the prefrontal cortex (PFC) was measured during three consecutive exposure sessions. N = 13 acrophobic volunteers were asked to walk on a virtual plank with a 6 m drop below. Changes in oxygenated (HbO) hemoglobin concentrations in the PFC were measured in three blocks using fNIRS. Consistent with previous functional magnetic resonance imaging (fMRI) studies, the analysis showed decreased activity in the DLPFC and MPFC during first exposure. The activity increased toward normal across three sessions. The study demonstrates potential efficacy of a method for measuring within-session neural response to virtual stimuli that could be replicated within clinics and research institutes, with equipment better suited to an ET session and at fraction of the cost, when compared to fMRI. This has application in widening access to, and increasing ecological validity of, immersive neuroimaging across understanding, diagnosis, assessment and treatment of, a range of mental disorders such as phobia, anxiety and PTSD or addictions

Generating intrafusal skeletal muscle fibres in vitro: Current state of the art and future challenges

Intrafusal fibres are a specialised cell population in skeletal muscle, found within the muscle spindle. These fibres have a mechano-sensory capacity, forming part of the monosynaptic stretch-reflex arc, a key component responsible for proprioceptive function. Impairment of proprioception and associated dysfunction of the muscle spindle is linked with many neuromuscular diseases. Research to-date has largely been undertaken in vivo or using ex vivo preparations. These studies have provided a foundation for our understanding of muscle spindle physiology, however, the cellular and molecular mechanisms which underpin physiological changes are yet to be fully elucidated. Therefrom, the use of in vitro models has been proposed, whereby intrafusal fibres can be generated de novo. Although there has been progress, it is predominantly a developing and evolving area of research. This narrative review presents the current state of art in this area and proposes the direction of future work, with the aim of providing novel pre-clinical and clinical applications

Neuregulin 1 Drives Morphological and Phenotypical Changes in C2C12 Myotubes: Towards De Novo Formation of Intrafusal Fibres In Vitro

Muscle spindles are sensory organs that detect and mediate both static and dynamic muscle stretch and monitor muscle position, through a specialised cell population, termed intrafusal fibres. It is these fibres that provide a key contribution to proprioception and muscle spindle dysfunction is associated with multiple neuromuscular diseases, aging and nerve injuries. To date, there are few publications focussed on de novo generation and characterisation of intrafusal muscle fibres in vitro. To this end, current models of skeletal muscle focus on extrafusal fibres and lack an appreciation for the afferent functions of the muscle spindle. The goal of this study was to produce and define intrafusal bag and chain myotubes from differentiated C2C12 myoblasts, utilising the addition of the developmentally associated protein, Neuregulin 1 (Nrg-1). Intrafusal bag myotubes have a fusiform shape and were assigned using statistical morphological parameters. The model was further validated using immunofluorescent microscopy and western blot analysis, directed against an extensive list of putative intrafusal specific markers, as identified in vivo. The addition of Nrg-1 treatment resulted in a 5-fold increase in intrafusal bag myotubes (as assessed by morphology) and increased protein and gene expression of the intrafusal specific transcription factor, Egr3. Surprisingly, Nrg-1 treated myotubes had significantly reduced gene and protein expression of many intrafusal specific markers and showed no specificity towards intrafusal bag morphology. Another novel finding highlights a proliferative effect for Nrg-1 during the serum starvation-initiated differentiation phase, leading to increased nuclei counts, paired with less myotube area per myonuclei. Therefore, despite no clear collective evidence for specific intrafusal development, Nrg-1 treated myotubes share two inherent characteristics of intrafusal fibres, which contain increased satellite cell numbers and smaller myonuclear domains compared with their extrafusal neighbours. This research represents a minimalistic, monocellular C2C12 model for progression towards de novo intrafusal skeletal muscle generation, with the most extensive characterisation to date. Integration of intrafusal myotubes, characteristic of native, in vivo intrafusal skeletal muscle into future biomimetic tissue engineered models could provide platforms for developmental or disease state studies, pre-clinical screening, or clinical applications

Office-Based Educational Handout for Influenza Vaccination: A Randomized Controlled Trial

This is the author accepted manuscript. The final version is available from American Academy of Pediatrics via the DOI in this recordData sharing statement: De-identified individual participant data will not be made available.OBJECTIVES: To assess the impact of a parent educational intervention about influenza disease on child vaccine receipt. METHODS: A convenience sample of parents of children ≥6 months old with a visit at 2 New York City pediatric clinics between August 2016 and March 2017 were randomly assigned (1:1:1) to receive either usual care, an educational handout about influenza disease that was based on local data, or an educational handout about influenza disease that was based on national data. Parents received the handout in the waiting room before their visit. Primary outcomes were child influenza vaccine receipt on the day of the clinic visit and by the end of the season. A multivariable logistic regression was used to assess associations between intervention and vaccination, with adjustment for variables that were significantly different between arms. RESULTS: Parents who received an intervention (versus usual care) had greater odds of child influenza vaccine receipt by the end of the season (74.9% vs 65.4%; adjusted odds ratio 1.68; 95% confidence interval: 1.06-2.67) but not on the day of the clinic visit. Parents who received the national data handout (versus usual care) had greater odds of child influenza vaccine receipt on the day of the clinic visit (59.0% vs 52.6%; adjusted odds ratio 1.79; 95% confidence interval: 1.04-3.08) but not by the end of the season. CONCLUSIONS: Providing an educational intervention in the waiting room before a pediatric provider visit may help increase child influenza vaccine receipt.European CommissionNIH - Ruth L. Kirschstein National Research Service Awar

Impact of commonly prescribed exercise interventions on platelet activation in physically inactive and overweight men.

The exercise paradox infers that, despite the well-established cardioprotective effects of repeated episodic exercise (training), the risk of acute atherothrombotic events may be transiently increased during and soon after an exercise bout. However, the acute impact of different exercise modalities on platelet function has not previously been addressed. We hypothesized that distinct modalities of exercise would have differing effects on in vivo platelet activation and reactivity to agonists which induce monocyte-platelet aggregate (MPA) formation. Eight middle-aged (53.5 ± 1.6 years) male participants took part in four 30 min experimental interventions (aerobic AE, resistance RE, combined aerobic/resistance exercise CARE, or no-exercise NE), in random order. Blood samples were collected before, immediately after, and 1 h after each intervention, and incubated with one of three agonists of physiologically/clinically relevant pathways of platelet activation (thrombin receptor activating peptide-6 TRAP, arachidonic acid AA, and cross-linked collagen-related peptide xCRP). In the presence of AA, TRAP, and xCRP, both RE and CARE evoked increases in MPAs immediately post-exercise (P < 0.01), whereas only AA significantly increased MPAs immediately after AE (P < 0.01). These increases in platelet activation post-exercise were transient, as responses approached pre-exercise levels by 1 h. These are the first data to suggest that exercise involving a resistance component in humans may transiently increase platelet-mediated thrombotic risk more than aerobic modalities