Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of ...various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration.
Curriculum design and specific topic selection for on-site practical courses in clinical disciplines with limited teaching time is challenging. An electronic learning supported curriculum based on ...the flipped classroom principle has a high potential to effectively gain knowledge and education along with improving practical experience. Here, we demonstrate the introduction of a flipped classroom curriculum for practical courses in Otorhinolaryngology (ORL) in real world practice to improve the on-site time management and students' experience.
Educational aims of our practical curriculum were analysed and rearranged into a flipped classroom (FC) framework. Core knowledge was taught preliminary based on a moodle platform in predominantly interactive formats. Two quasi-randomized groups were formed with 212 participants either receiving or not receiving access to the e-learning program to reduce a potential allocation bias to the e-learning group. All students completed a questionnaire with learning related items. Focusing the study on the intervention group, we investigated if students using the flipped classroom more often felt better prepared for the practical course.
The online learning platform was highly accepted and frequently used by 66% of participating students in the e-learning group. Students with frequent use of our e-learning platform significantly felt better prepared for the practical course (p = 0.001). The far majority of all students supports the idea of further development of e-learning. More than 70% were generally interested in ORL. Handouts were the overall most important learning resource and more than 50% relied solely on them.
Flipped classroom curricula can save time and help improving the on-site experience in practical courses especially in smaller surgical disciplines. The acceptance of digital learning is high, and most students rely on handouts for learning ORL, emphasizing the need for guidance by the teacher e.g. through electronic learning. Our results underline the high potential of FC to address teaching challenges for smaller medical disciplines with limited teaching time like ORL.
Sensory restoration by optogenetic neurostimulation provides a promising future alternative to current electrical stimulation approaches. So far, channelrhodopsins (ChRs) typically contain a ...C-terminal fluorescent protein (FP) tag for visualization that potentially poses an additional risk for clinical translation. Previous work indicated a reduction of optogenetic stimulation efficacy upon FP removal. Here, we further optimized the fast-gating, red-light-activated ChR f-Chrimson to achieve efficient optogenetic stimulation in the absence of the C-terminal FP. Upon FP removal, we observed a massive amplitude reduction of photocurrents in transfected cells in vitro and of optogenetically evoked activity of the adeno-associated virus (AAV) vector-transduced auditory nerve in mice in vivo. Increasing the AAV vector dose restored optogenetically evoked auditory nerve activity but was confounded by neural loss. Of various C-terminal modifications, we found the replacement of the FP by the Kir2.1 trafficking sequence (TSKir2.1) to best restore both photocurrents and optogenetically evoked auditory nerve activity with only mild neural loss few months after dosing. In conclusion, we consider f-Chrimson-TSKir2.1 to be a promising candidate for clinical translation of optogenetic neurostimulation such as by future optical cochlear implants.
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Zerche and colleagues developed a procedure for Channelrhodopsin fluorescent tag replacement and demonstrated its efficacy-enhancing effect for future optogenetic hearing restoration. f-Chrimson-TSKir2.1 enabled red-light-controlled spiking of mouse spiral ganglion neurons at near physiological rates while considerably minimizing the risk for adverse effect.
Abstract
Background
The availability and popularity of laptops, tablet PCs and smartphones in private and work environments offers considerable potential for reasonably integrating blended learning ...formats into structured medical learning environments. The promising educational principle of the flipped classroom (FC) provides the opportunity to effectively combine e-learning and face-to-face teaching within a single framework. However, similar to most blended learning formats, the FC requires a solid groundwork of structured digitized learning content. As rearranging a whole curriculum is intense and time consuming, physicians occupied simultaneously in clinical practice and teaching may be confronted with a lack of time during this process.
Methods
We developed two straightforward approaches to transforming a pre-existing, lecture-based otolaryngology curriculum into interactive videos within a Moodle learning management system. Special attention was given to reducing individual working time for medical professionals. Thus, while one approach was mainly guided by a medical professional to control the content-related quality of video processing, we investigated an alternative approach outsourcing work to a technician. Afterwards, the working time was analysed and compared. The resulting videos were revised with the H5P plugin for moodle to adjust the content where necessary.
Results
We identified a fast-track approach for creating structured e-learning content suitable for flipped-classroom-based lectures, other blended learning formats, or even providing a whole curriculum online. The alternative approach significantly reduced working time for medical professionals but did not impair the content-related quality significantly.
Conclusions
The use of H5P interactive tools via Moodle LMS provides a major procedural benefit by allowing the easy adjustment of pre-existing video material into suitable online content. Reasonably outsourcing work to technicians can significantly reduce the working time of medical professionals without decreasing the quality of learning content. The presented workflow can be used as a flexible approach for flipped classroom frameworks or other blended learning strategies where interactive videos are applicable.
Sensorineural hearing impairment is the most frequent form of hearing impairment affecting 1–2 in 1000 newborns and another 1 in 1000 adolescents. More than 50% of congenital hearing impairment is of ...genetic origin and some forms of monogenic deafness are likely targets for future gene therapy. Good progress has been made in clinical phenotyping, genetic diagnostics, and counselling. Disease modelling, e.g. in transgenic mice, has helped elucidate disease mechanisms underlying genetic hearing impairment and informed clinical phenotyping in recent years. Clinical management of paediatric hearing impairment involves hearing aids, cochlear or brainstem implants, signal-to-noise improvement in educational settings, speech therapy, and sign language. Cochlear implants, for example, have much improved the situation of profoundly hearing impaired and deaf children. Nonetheless there remains a major unmet clinical need for improving hearing restoration. Preclinical studies promise that we will witness clinical trials on gene therapy and a next generation of cochlear implants during the coming decade. Moreover, progress in generating sensory hair cells and neurons from stem cells spurs disease modelling, drug screening, and regenerative approaches. This review briefly summarizes the pathophysiology of paediatric hearing impairment and provides an update on the current preclinical development of innovative approaches toward improved hearing restoration.
Objective
Evaluation of the self‐perceived hearing impairment and performance after cochlear implantation in patients with definite Menière's disease (MD).
Patients and Methods
Seventeen unilaterally ...or bilaterally profoundly hearing‐impaired patients suffering from MD who received a cochlear implantat (CI) were eligible for inclusion in this study. Their self‐perceived hearing impairment using the short Speech Spatial and Qualities of Hearing Scale (SSQ12) as well as their performance in speech perception (German language Freiburger mono‐ and multisyllable test, Oldenburger sentence test) were compared with a best‐matched control group of non‐MD patients up to 24 months of follow‐up.
Results
MD patients improved significantly in perception of monosyllables presented at 65 dBSPL, from preoperatively best aided 18.2% 2.4, 34.0 to 51.7% 39.4, 63.9 1 year after cochlear implantation (mean 95% confidence interval). Their performance approached the matched controls with 63.2% 55.7, 70.8. Monosyllables presented at a lower intensity of 55 dBSPL revealed a significant underperformance of the MD patients (21.1% 12.6, 29.6) in contrast to the non‐MD controls (39.1% 30.9, 47.4) 12 months post‐CI. Self‐assessed hearing disability was significantly more pronounced in MD patients with a mean total SSQ12 score of 3.6 2.4, 4.9 in comparison to 6.1 5.4, 6.8 of the matched non‐MD controls after 12 months of cochlear implantation.
Conclusion
Cochlear implantation substantially improves hearing capabilities in profoundly hearing‐impaired patients with MD, but they tend to underperform in comparison to non‐MD patients at least at lower sound pressure levels. This is likely one reason for the poorer self‐assessed hearing function of cochlear implanted MD patients.
Level of Evidence
3, retrospective, nonrandomized follow‐up study.
The current study evaluates self‐perceived hearing function using the SSQ12 as well as speech perception in cochlear implanted patients with Menière's disease. It reveals greater self‐assessed hearing impairment with an accompanying worse speech perception at lower sound pressure levels of Menière patients in comparison to a best‐matched control group of non‐Menière CI patients.
Objective
Investigation of the gustatory function in a large cohort of cochlear implanted patients using lateralized taste‐strip tests.
Patients and Methods
One hundred and seven unilaterally or ...bilaterally profoundly hearing impaired or deaf patients who received cochlear implants (n = 113) were included in this study. Data on gustometry, subjective gustatory dysfunction, and the detailed surgical procedure were acquired retrospectively. Gustatory function, assessed using lateralized taste‐strip tests, was performed the day before, 3 days after cochlear implantation, and on the day of the initial CI adjustment (39 days ±7.3 SD).
Results
Averaged taste‐strip scores of the cohort declined significantly from preoperatively 12.3 11.8; 12.7 (mean 95% confidence intervals) to 10.5 9.7; 11.2 on the implanted side about 6 weeks after surgery. Patients with intraoperatively exposed and rerouted, or a severed, chorda tympani nerve (CTN) showed significantly reduced unilateral postoperative scores (10.1 8.8; 11.4 and 9.3 8.1; 10.5, respectively), when compared to not exposing or to leaving a bony layer over the CTN. Total taste‐strip test scores showed a significant decline 6 weeks postoperatively in CI‐patients expressing a subjective gustatory dysfunction (from 23.6 21.4; 25.8 to 17.5 14.2; 20.8), as opposed to patients with a documented subjectively normal taste.
Conclusion
We consider postoperative gustatory dysfunction as a relevant side effect post cochlear implantation, at least within the first month. Taste‐strip based gustometry is a suitable diagnostic tool to assess taste function in CI patients and is recommended to be performed routinely.
Level of Evidence
3, retrospective, nonrandomized follow‐up study.
Zusammenfassung
Hintergrund
Plattenbasierte Ankersysteme zur fazialen Epithesenversorgung bieten gegenüber extraoralen Einzeltitanimplantaten Vorteile hinsichtlich einer flexibleren Wahl knöcherner ...Verankerungspunkte und höherer Stabilität. Nachteile werden in einer aufwendigen individuellen intraoperativen Anpassung der Plattensysteme am meist schlecht zugänglichen Knochen deutlich. Wir stellen eine Methode vor, diese Nachteile zu überwinden und die Vorteile plattenbasierter Systeme stärker auszuspielen.
Methodik
Das knöcherne Mittegesicht eines Patienten mit erfolgter Rhinektomie bei Karzinom des Naseneingangs wurde anhand der präoperativen Computertomographie als virtuelles 3‑D-Modell rekonstruiert. Die verwendete Open-Source-Software (3-D-Sclicer) ermöglichte die einfache und schnelle Rekonstruktion sowie Anpassung zum Druck des 3‑D-Modells mittels transparenten Kunststoffs (MED610; stratasys Ltd., MN, USA).
Ergebnisse
Die als Epithesenanker verwendete Titan-Brückenplatte (MEDICON) konnte am 3‑D-Druck des Mittelgesichts äußerst präzise vorangepasst werden. Wichtige anatomische Strukturen wurden geschont und die Verschraubungspunkte entsprechend der gegebenen Knochendicke gewählt. Die Implantation der vorangepassten Titanplatte erfolgte komplikationslos ohne weitere intraoperative Anpassungen.
Schlussfolgerung
Die Voranpassung plattenbasierter Ankersysteme für faziale Epithesen am 3‑D-Druck des Mittelgesichts überwindet deren Nachteile einer aufwendigen ggf. unpräzisen intraoperativen individuellen Anpassung. Diese Methode spielt die Vorteile der besseren Kraftverteilung durch mehr mögliche Verschraubungen, auch in dünnerem Knochen, weiter aus und kann somit Implantatlockerungen vorbeugen. Zudem ermöglicht die Voranpassung am 3‑D-Modell die bessere Identifikation und Schonung wichtiger anatomischer Strukturen und spart Op.-Zeit ein.
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