Prosessuell generering av medisinske kasuistikker - Et begrenset eksperiment

BACKGROUND: Procedural generation is a technique used in video game development where algorithms are used to create game assets such as landscapes and foliage. It enables game studios to create greater amounts of content than would be feasible using artists alone. For medical students, case books offer a way to apply and challenge their theoretical knowledge of diagnostics and therapy. Could procedural generation be used for generating medical cases? An unstructured search of medical literature reveals little mention of this method being explored. This project implemented and tested a limited experiment to see if the technique was applicable also in this field. METHODS: Three software tools were written: (1) A modelling tool to describe the variety in a condition s presentation, findings, lab results etc. (2) A tool that picked elements from these models in a predictable way and outputted medical cases as datasets. (3) A browser based client that presented an excerpt of a random case and asked medical students to arrive at diagnosis and treatment by requesting additional information about the patient from the case dataset. To incentivize rational choices in what information to retrieve, each request came at a cost in terms of virtual money, time and patient discomfort. After solving each case a score was presented. Students were recruited through social media to test the client tool and answer a survey about their experience. RESULTS: There were 30 respondents. Significant bias possibilities make the results unreliable. The students reported the system to be interesting (87%), useful (87%), fun (77%) and exciting (77%). 23% found the system difficult. Less than 14% found it frustrating , overwhelming , confusing or boring . Most (> 75%) perceived the medical quality to be good. The same number responded they would use such a system again, and recommended it to others, if it had more content. A similar number believed it would make them better equipped to make real diagnostic considerations, and that it would improve retention of the material studied in books. CONCLUSION: Procedural generation may be applied in medical education to generate dataset based medical cases, but significant challenges exist. Generating cases with multi- morbidity and polypharmacy appears especially difficult. Development may be costly and consume significant amounts of expert time

Aquaporin-4-independent volume dynamics of astroglial endfeet during cortical spreading depression

Cortical spreading depression (CSD) is a slowly propagating wave of depolarization of gray matter. This phenomenon is believed to underlie the migraine aura and similar waves of depolarization may exacerbate injury in a number of neurological disease states. CSD is characterized by massive ion dyshomeostasis, cell swelling, and multiphasic blood flow changes. Recently, it was shown that CSD is associated with a closure of the paravascular space (PVS), a proposed exit route for brain interstitial fluid and solutes, including excitatory and inflammatory substances that increase in the wake of CSD. The PVS closure was hypothesized to rely on swelling of astrocytic endfeet due to their high expression of aquaporin‐4 (AQP4) water channels. We investigated whether CSD is associated with swelling of endfeet around penetrating arterioles in the cortex of living mice. Endfoot cross‐sectional area was assessed by two‐photon microscopy of mice expressing enhanced green fluorescent protein in astrocytes and related to the degree of arteriolar constriction. In anesthetized mice CSD triggered pronounced endfoot swelling that was short‐lasting and coincided with the initial arteriolar constriction. Mice lacking AQP4 displayed volume changes of similar magnitude. CSD‐induced endfoot swelling and arteriolar constriction also occurred in awake mice, albeit with faster kinetics than in anesthetized mice. We conclude that swelling of astrocytic endfeet is a robust event in CSD. The early onset and magnitude of the endfoot swelling is such that it may significantly delay perivascular drainage of interstitial solutes in neurological conditions where CSD plays a pathophysiological role

Begonia - a two-photon imaging analysis pipeline for astrocytic Ca2+ signals

Imaging the intact brain of awake behaving mice without the dampening effects of anesthesia, has revealed an exceedingly rich repertoire of astrocytic Ca 2+ signals. Analyzing and interpreting such complex signals pose many challenges. Traditional analyses of fluorescent changes typically rely on manually outlined static region-of-interests, but such analyses fail to capture the intricate spatiotemporal patterns of astrocytic Ca 2+ dynamics. Moreover, all astrocytic Ca 2+ imaging data obtained from awake behaving mice need to be interpreted in light of the complex behavioral patterns of the animal. Hence processing multimodal data, including animal behavior metrics, stimulation timings, and electrophysiological signals is needed to interpret astrocytic Ca 2+ signals. Managing and incorporating these data types into a coherent analysis pipeline is challenging and time-consuming, especially if research protocols change or new data types are added. Here, we introduce Begonia, a MATLAB-based data management and analysis toolbox tailored for the analyses of astrocytic Ca 2+ signals in conjunction with behavioral data. The analysis suite includes an automatic, event-based algorithm with few input parameters that can capture a high level of spatiotemporal complexity of astrocytic Ca 2+ signals. The toolbox enables the experimentalist to quantify astrocytic Ca 2+ signals in a precise and unbiased way and combine them with other types of time series data

Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We show that astrocytic Ca2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Finally, genetic ablation of an important astrocytic Ca2+ signaling pathway impairs slow wave sleep and results in an increased number of microarousals, abnormal brain rhythms, and an increased frequency of slow wave sleep state transitions and sleep spindles. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep

Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We show that astrocytic Ca2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Finally, genetic ablation of an important astrocytic Ca2+ signaling pathway impairs slow wave sleep and results in an increased number of microarousals, abnormal brain rhythms, and an increased frequency of slow wave sleep state transitions and sleep spindles. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep