Spinster (Spin) in Drosophila or Spinster homolog 1 (Spns1) in vertebrates is a putative lysosomal H+-carbohydrate transporter, which functions at a late stage of autophagy. The Spin/Spns1 defect ...induces aberrant autolysosome formation that leads to embryonic senescence and accelerated aging symptoms, but little is known about the mechanisms leading to the pathogenesis in vivo. Beclin 1 and p53 are two pivotal tumor suppressors that are critically involved in the autophagic process and its regulation. Using zebrafish as a genetic model, we show that Beclin 1 suppression ameliorates Spns1 loss-mediated senescence as well as autophagic impairment, whereas unexpectedly p53 deficit exacerbates both of these characteristics. We demonstrate that 'basal p53' activity plays a certain protective role(s) against the Spns1 defect-induced senescence via suppressing autophagy, lysosomal biogenesis, and subsequent autolysosomal formation and maturation, and that p53 loss can counteract the effect of Beclin 1 suppression to rescue the Spns1 defect. By contrast, in response to DNA damage, 'activated p53' showed an apparent enhancement of the Spns1-deficient phenotype, by inducing both autophagy and apoptosis. Moreover, we found that a chemical and genetic blockage of lysosomal acidification and biogenesis mediated by the vacuolar-type H+-ATPase, as well as of subsequent autophagosome-lysosome fusion, prevents the appearance of the hallmarks caused by the Spns1 deficiency, irrespective of the basal p53 state. Thus, these results provide evidence that Spns1 operates during autophagy and senescence differentially with Beclin 1 and p53.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Spinster (Spin) in Drosophila or Spinster homolog 1 (Spns1) in vertebrates is a putative lysosomal H+-carbohydrate transporter, which functions at a late stage of autophagy. The Spin/Spns1 defect ...induces aberrant autolysosome formation that leads to embryonic senescence and accelerated aging symptoms, but little is known about the mechanisms leading to the pathogenesis in vivo. Beclin 1 and p53 are two pivotal tumor suppressors that are critically involved in the autophagic process and its regulation. Using zebrafish as a genetic model, we show that Beclin 1 suppression ameliorates Spns1 loss-mediated senescence as well as autophagic impairment, whereas unexpectedly p53 deficit exacerbates both of these characteristics. We demonstrate that 'basal p53' activity plays a certain protective role(s) against the Spns1 defect-induced senescence via suppressing autophagy, lysosomal biogenesis, and subsequent autolysosomal formation and maturation, and that p53 loss can counteract the effect of Beclin 1 suppression to rescue the Spns1 defect. By contrast, in response to DNA damage, 'activated p53' showed an apparent enhancement of the Spns1-deficient phenotype, by inducing both autophagy and apoptosis. Moreover, we found that a chemical and genetic blockage of lysosomal acidification and biogenesis mediated by the vacuolar-type H+-ATPase, as well as of subsequent autophagosome-lysosome fusion, prevents the appearance of the hallmarks caused by the Spns1 deficiency, irrespective of the basal p53 state. Thus, these results provide evidence that Spns1 operates during autophagy and senescence differentially with Beclin 1 and p53.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives:
Gels composed of carboxymethylcellulose (CMC) and cross-linked hyaluronic acid are commonly used as temporary or resorbable injectable materials for vocal fold medialization. However, ...there is limited information about tissue injection patterns, soft tissue reaction, degradation, and residence time, particularly for the newer CMC gels.
Study Design:
Prospective, laboratory.
Methods:
Ten canines underwent paraglottic (deep to the vocal ligament) microlaryngoscopic injection with about 100 µL (0.1 mL) of cross-linked hyaluronic acid (Restylane) in the right vocal fold and about 100 µl (0.1 mL) of CMC gel in the left vocal fold. Two commercial CMC gels of similar formulation (Prolaryn Gel and Renú Gel) were used in 5 animals each. Two subjects were sacrificed for histologic analysis at 3, 13, 29, 42, and 55 days.
Results:
Histology showed that injected Restylane formed cohesive ovoid-shaped aggregated implants with minimal dispersion, inflammation, or cellular invasion in all subjects. Approximately 86% of Restylane injected remained at 8 weeks, as estimated from postmortem, high-resolution magnetic resonance imaging scans. In contrast, histology showed that both CMC gels dispersed widely through fascial planes during and after injection within and outside the thyroarytenoid muscle fascicles. There was a robust macrophage and histiocyte phagocytic response, with moderate to severe inflammation noted around residual CMC gel at early time points, and at 6 to 8 weeks, very little free gel was observed.
Conclusions:
None of the studied materials induced a clinical inflammatory reaction on laryngoscopy such that they would be considered problematic or dangerous. Restylane demonstrated superior injection localization, tissue compatibility, and residence time. Both CMC gels did not localize well in the paraglottic region, and there was a robust inflammatory response, with clearance by macrophages and short residence time. These results suggest that CMC gels may have a more limited application than previously thought for vocal fold medialization in patients in whom the injection is being used to achieve voice enhancement while awaiting reinnervation.
Level of Evidence: NA
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract
Movement intention detection using electroencephalography (EEG) is a challenging but essential component of brain–computer interfaces (BCIs) for people with motor disabilities.
Objective.
...The goal of this study is to develop a new experimental paradigm to perform asynchronous online detection of movement based on low-frequency time-domain EEG features, concretely on movement-related cortical potentials. The paradigm must be easily transferable to people without any residual upper-limb movement function and the BCI must be independent of upper-limb movement onset measurements and external cues.
Approach
. In a study with non-disabled participants, we evaluated a novel BCI paradigm to detect self-initiated reach-and-grasp movements. Two experimental conditions were involved. In one condition, participants performed reach-and-grasp movements to a target and simultaneously shifted their gaze towards it. In a control condition, participants solely shifted their gaze towards the target (oculomotor task). The participants freely decided when to initiate the tasks. After eye artefact correction, the EEG signals were time-locked to the saccade onset and the resulting amplitude features were exploited on a hierarchical classification approach to detect movement asynchronously.
Main results
. With regards to BCI performance, 54.1% (14.4% SD) of the movements were correctly identified, and all participants achieved a performance above chance-level (around 12%). An average of 21.5% (14.1% SD) of the oculomotor tasks were falsely detected as upper-limb movement. In an additional rest condition, 1.7 (1.6 SD) false positives per minute were measured. Through source imaging, movement information was mapped to sensorimotor, posterior parietal and occipital areas.
Significance
. We present a novel approach for movement detection using EEG signals which does not rely on upper-limb movement onset measurements or on the presentation of external cues. The participants’ behaviour closely matches the natural behaviour during goal-directed reach-and-grasp movements, which also constitutes an advantage with respect to current BCI protocols.
Introduction:
Endotracheal (ET) intubation is a common cause of acquired glottic stenosis. Severe cases often require an irreversible arytenoidectomy/cordectomy, which typically results in poor voice ...quality. Adult human cadaver larynges were studied to gain insights about ET tube–induced posterior glottic injuries, hoping to create a less invasive remedy.
Study Design:
Human cadaver investigation and case reports.
Methods:
Microlaryngeal assessments were done on 10 human cadaver larynges (5 men, 5 women) with and without ET tubes. After supracricoid soft tissue resection, measurements were obtained, including the distance between the outer diameter of the ET tube and the medial aspect of the cricoarytenoid joint facet. Additionally, measurements of the circumferential arc of differently sized ET tubes were made alongside both cricoarytenoid joint capsules. This information was used to design a silastic stent that would function as a self-retaining interarytenoid spring to treat posterior glottic stenosis in 5 patients. Four of 5 patients included in the clinical study were tracheotomy dependent, primarily because of glottic stenosis. The human surgical technique is described in detail.
Results:
The shortest distance between the outer diameter of the ET tube to the medial cricoid facet averaged 5.02 mm in men and 3.62 mm in women. On the basis of the diameter of the intralaryngeal component of the initially round stent, and the position of the cricoarytenoid joint facets, the interarytenoid spring would have a subtended arc between 110° and 175°. These data helped fashion parameters for modifying a conventional T-tube to form a new self-retaining silastic interarytenoid spring. The first 5 human cases have been successful, allowing effective tracheotomy tube decannulation and excellent voice quality.
Conclusions:
The anatomic investigation herein provided key insights into ET tube–induced glottic stenosis and facilitated a new straightforward procedure to surgically improve the airway yet preserve excellent vocal function in patients with acquired glottic stenosis.
Level of Evidence: NA
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
To assess the importance of sewage treatment plant effluents on fish health, we studied gudgeon in two rivers in the Swiss midlands (Canton Lucerne). Both rivers receive pollution from diffuse ...sources, while one also receives the effluent of a sewage treatment plant. Male and female gudgeon during and outside of the spawning season were compared with respect to reproductive parameters and health status across both rivers as well as upstream and downstream of the STP. Several biomarkers were studied, including cytochrome P4501A, 7‐ethoxyresorufin‐O‐deethylase, plasma vitellogenin, ovotestis, lipid, liver histology, condition factor, gonadosomatic index, splenosomatic index, parasites of spleen and liver, population structure, and species diversity. Gudgeons of both rivers exhibited signs of a moderately impaired health status. By a stepwise backward analysis, the cytochrome P4501A content, the splenosomatic index, and the incidence of parasites in the liver were found to provide the best discrimination of the three sampling sites. Evidence of a significant elevation in response to the sewage treatment plant effluent was found neither in vitellogenin concentration nor in the ovotestis rate. While population structure was analyzed upstream and downstream of the sewage treatment plant, only gudgeons of the latter site revealed a disturbed population structure, most probably caused by a former nitrite discharge.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bibian et al. show in their recent paper (Bibián et al. 2021) that eye and head movements can affect the EEG-based classification in a reaching motor task. These movements can generate artefacts that ...can cause an overoptimistic estimation of the classification accuracy. They speculate that such artefacts jeopardise the interpretation of the results from several motor decoding studies including our study (Ofner et al. 2017). While we endorse their warning about artefacts in general, we do have doubts whether their work supports such a statement with respect to our study. We provide in this commentary a more nuanced contextualization of our work presented in Ofner et al. and the type of artefacts investigated in Bibian et al.
Spinal cord injury (SCI) can disrupt the communication pathways between the brain and the rest of the body, restricting the ability to perform volitional movements. Neuroprostheses or robotic arms ...can enable individuals with SCI to move independently, improving their quality of life. The control of restorative or assistive devices is facilitated by brain-computer interfaces (BCIs), which convert brain activity into control commands. In this paper, we summarize the recent findings of our research towards the main aim to provide reliable and intuitive control. We propose a framework that encompasses the detection of goal-directed movement intention, movement classification and decoding, error-related potentials detection and delivery of kinesthetic feedback. Finally, we discuss future directions that could be promising to translate the proposed framework to individuals with SCI.
Restoring the ability to reach and grasp can dramatically improve quality of life for people with cervical spinal cord injury (SCI). The main challenge in restoring independent reaching and grasping ...in patients is to develop assistive technologies with intuitive and non-invasive user interfaces. We believe that this challenge can be met by directly translating movement-related brain activity into control signals. During the last decade, we have conducted research on EEG-based brain-computer interfaces (BCIs) for the decoding of movement parameters, such as trajectories and targets. Although our findings are promising, the control is still unnatural. Therefore, we surmise that natural and intuitive control of neuroprostheses could be achieved by developing a novel control framework that incorporates detection of goal directed movement intention, movement decoding, identifying the type of grasp, error potentials detection and delivery of feedback.
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