Development and optimisation of in vitro sonodynamic therapy for glioblastoma.

Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.

Emotional visual stimuli and simulated laparoscopic surgical performance: A pilot cohort study.

BACKGROUND: Exposure to stress prior to or during surgery can negatively impact performance. Management of stress is an essential non-technical skill required for safe practice. The effects of exposure to emotional visual stressors on surgical performance are poorly understood. This study aims to develop a model to investigate effects of emotive visual stimuli on simulated laparoscopic performance. METHODS AND MATERIALS: A single-centre cohort study. Thirty novice, simulator-naïve medical students were randomly allocated to view either positive, negative, or neutral emotional images (sourced from validated image registry). Participants focused for 5 s on the image before completing a peg-threading laparoscopic task. Time, instrument distance, speed, acceleration, motion smoothness, and ambidexterity were recorded automatically with instrument tracking software. 8 task cycles were completed; 3 control practices followed by 5 with the stimuli, according to group allocation. RESULTS: The final performance metrics of students (time, distance, speed, and motion smoothness) were not significantly different when comparing positive and neutral stimuli groups to those shown negative stimuli. However, changes were seen in the rate of performance improvements (positive: p = 0.711, p = 0.837, p = 0.297, and p = 0.393) (neutral: p = 0.285, p = 0.918, p = 0.835, and p = 0.396). Participation improved performance metrics overall (p=<0.001, p=<0.001, p = 0.088, p = 0.025, p=<0.001). CONCLUSION: Model systems may be valuable for investigating the impact of stress on surgeon performance. The effect of emotive visual stimuli on surgical performance is complex. This model may aid the further exploration of these relationships and ultimately can provide an environment in which surgeons can develop strategies to mitigate the adverse effect of stressors.

The digital Cullen chart: a red colour perimetry aid for visual field examination.

BACKGROUND: 30 years ago, a paper chart was developed in Edinburgh by Cullen et al. and validated as a swift, supplementary method for perimetric evaluation of visual fields. We have re-developed this concept in digital form (on smartphone screen) and assessed its sensitivity and specificity in detecting visual field loss, by comparison with formal machine-based perimetry. METHODS: Patients with sellar and parasellar tumours, being managed in a single neurosurgical centre, underwent formal visual field perimetry as part of standard care. They also underwent assessment using the smartphone-based Cullen chart. 37 eye testing episodes were assessed, incorporating pre- and post-treatment assessments for a range of potentially compressive pathologies (non-secretory and secretory pituitary adenoma, craniopharyngioma, and parasellar meningioma). The smartphone-based Cullen chart was compared with formal machine-based perimetry for concordance in detecting visual field loss. RESULTS: The digital Cullen chart had a sensitivity of 75% and specificity of 98% compared with machine-based perimeters. The positive predictive value was 93% and the negative predictive value was 92%. CONCLUSIONS: For the visual field assessment of patients with sellar/parasellar tumours, this simple and swift smartphone-based chart shows good concordance with machine-based perimeters. With amendments to the user interface, there may be potential for telemetric patient-led visual field monitoring.