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  • Al-Husseini, Ali, et al. (författare)
  • Long-term postural control in elite athletes following mild traumatic brain injury
  • 2022
  • Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Traumas to the head and neck are common in sports and often affects otherwise healthy young individuals. Sports-related concussions (SRC), defined as a mild traumatic brain injury (mTBI), may inflict persistent neck and shoulder pain, and headache, but also more complex symptoms, such as imbalance, dizziness, and visual disturbances. These more complex symptoms are difficult to identify with standard health care diagnostic procedures.Objective: To investigate postural control in a group of former elite athletes with persistent post-concussive symptoms (PPCS) at least 6 months after the incident.Method: Postural control was examined using posturography during quiet stance and randomized balance perturbations with eyes open and eyes closed. Randomized balance perturbations were used to examine motor learning through sensorimotor adaptation. Force platform recordings were converted to reflect the energy used to maintain balance and spectrally categorized into total energy used, energy used for smooth corrective changes of posture (i.e., <0.1 Hz), and energy used for fast corrective movements to maintain balance (i.e., >0.1 Hz).Results: The mTBI group included 20 (13 males, mean age 26.6 years) elite athletes with PPCS and the control group included 12 athletes (9 males, mean age 26.4 years) with no history of SRC. The mTBI group used significantly more energy during balance perturbations than controls: +143% total energy, p = 0.004; +122% low frequency energy, p = 0.007; and +162% high frequency energy, p = 0.004. The mTBI subjects also adapted less to the balance perturbations than controls in total (18% mTBI vs. 37% controls, p = 0.042), low frequency (24% mTBI vs. 42% controls, p = 0.046), and high frequency (6% mTBI vs. 28% controls, p = 0.040). The mTBI subjects used significantly more energy during quiet stance than controls: +128% total energy, p = 0.034; +136% low-frequency energy, p = 0.048; and +109% high-frequency energy, p = 0.015.Conclusion: Athletes with previous mTBI and PPCS used more energy to stand compared to controls during balance perturbations and quiet stance and had diminished sensorimotor adaptation. Sports-related concussions are able to affect postural control and motor learning.
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  • Al-Shudifat, Abdul Rahman Mohummad, et al. (författare)
  • A Patient-Assessed Morbidity to Evaluate Outcome in Surgically Treated Vestibular Schwannomas
  • 2016
  • Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750. ; 94, s. 2-550
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Outcome after treatment of vestibular schwannomas can be evaluated by health providers as mortality, recurrence, performance, and morbidity. Because mortality and recurrence are rare events, evaluation has to focus on performance and morbidity. The latter has mostly been reported by health providers. In the present study, we validate 2 new scales for patient-assessed performance and morbidity in comparison with different outcome tools, such as quality of life (QOL) (European Quality of Life-5 dimensions [EQ-5D]), facial nerve score, and work capacity.METHODS: There were 167 total patients in a retrospective (n = 90) and prospective (n = 50) cohort of surgically treated vestibular schwannomas. A new patient-assessed morbidity score (paMS), a patient-assessed Karnofsky score (paKPS), the patient-assessed QOL (EQ-5D) score, work capacity, and the House-Brackmann facial nerve score were used as outcome measures. Analysis of paMS components and their relation to other outcomes was done as uni- and multivariate analysis.RESULTS: All outcome instruments, except EQ-5D and paKPS, showed a significant decrease postoperatively. Only the facial nerve score (House-Brackmann facial nerve score) differed significantly between the retrospective and prospective cohorts. Out of the 16 components of the paMS, hearing dysfunction, tear dysfunction, balance dysfunction, and eye irritation were most often reported. Both paMS and EQ-5D correlated significantly with work capacity.CONCLUSIONS: Standard QOL and performance instruments may not be sufficiently sensitive or specific to measure outcome at the cohort level after surgical treatment of vestibular schwannomas. A morbidity score may yield more detailed information on symptoms that can be relevant for rehabilitation and occupational training after surgery.
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  • Andeer, Robin, et al. (författare)
  • Chanjo : Clincal grade sequence coverage analysis
  • 2020
  • Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Coverage analysis is essential when analysing massive parallel sequencing (MPS) data. The analysis indicates existence of false negatives or positives in a region of interest or poorly covered genomic regions. There are several tools that have excellent performance when doing coverage analysis on a few samples with predefined regions. However, there is no current tool for collecting samples over a longer period of time for aggregated coverage analysis of multiple samples or sequencing methods. Furthermore, current coverage analysis tools do not generate customized coverage reports or enable exploratory coverage analysis without extensive bioinformatic skill and access to the original alignment files. We present Chanjo, a user friendly coverage analysis tool for persistent storage of coverage data, that, accompanied with Chanjo Report, produces coverage reports that summarize coverage data for predefined regions in an elegant manner. Chanjo Report can produce both structured coverage reports and dynamic reports tailored to a subset of genomic regions, coverage cut-offs or samples. Chanjo stores data in an SQL database where thousands of samples can be added over time, which allows for aggregate queries to discover problematic regions. Chanjo is well tested, supports whole exome and genome sequencing, and follows common UNIX standards, allowing for easy integration into existing pipelines. Chanjo is easy to install and operate, and provides a solution for persistent coverage analysis and clinical-grade reporting. It makes it easy to set up a local database and automate the addition of multiple samples and report generation. To our knowledge there is no other tool with matching capabilities. Chanjo handles the common file formats in genetics, such as BED and BAM, and makes it easy to produce PDF coverage reports that are highly valuable for individuals with limited bioinformatic expertise. We believe Chanjo to be a vital tool for clinicians and researchers performing MPS analysis.
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  • Andersson, Gert, et al. (författare)
  • Neck vibration causes short-latency electromyographic activation of lower leg muscles in postural reactions of the standing human.
  • 2002
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 122:3, s. 284-288
  • Tidskriftsartikel (refereegranskat)abstract
    • To study how quickly cervical proprioceptive information induced muscular responses in the lower leg to control posture in the standing human we investigated lower leg muscle electromyography and force-plate data from 10 healthy normal subjects, when perturbed by posterior neck muscle vibration. At the onset of vibration the tibialis anterior muscle was activated at latencies of 70-100 ms whilst the triceps surae muscle was inhibited at the same latencies. At offset the opposite pattern was observed. These findings suggest that a short-latency integrative system, rather than a direct reflex, mediates the cervical influence on posture. The short latencies also imply that activation of postural muscles in response to vibration towards the neck muscles occurs faster than would be expected if it was caused only by a perceptive illusion of movement.
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  • Bertilsson, Johan, et al. (författare)
  • Stress Levels Escalate When Repeatedly Performing Tasks Involving Threats
  • 2019
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 10, s. 1562-1562
  • Tidskriftsartikel (refereegranskat)abstract
    • Police work may include performing repeated tasks under the influence of psychological stress, which can affect perceptual, cognitive and motor performance. However, it is largely unknown how repeatedly performing stressful tasks physically affect police officers in terms of heart rate and pupil diameter properties. Psychological stress is commonly assessed by monitoring the changes in these biomarkers. Heart rate and pupil diameter was measured in 12 male police officers when performing a sequence of four stressful tasks, each lasting between 20 and 130 s. The participants were first placed in a dimly illuminated anteroom before allowed to enter a brightly lit room where a scenario was played out. After each task was performed, the participants returned to the anteroom for about 30 s before performing the next sequential task. Performing a repeated sequence of stressful tasks caused a significant increase in heart rate (p = 0.005). The heart rate started to increase already before entering the scenario room and was significantly larger just after starting the task than just before starting the task (p < 0.001). This pattern was more marked during the first tasks (p < 0.001). Issuance of a verbal "abort" command which terminated the tasks led to a significant increase of heart rate (p = 0.002), especially when performing the first tasks (p = 0.002). The pupil diameter changed significantly during the repeated tasks during all phases but in a complex pattern where the pupil diameter reached a minimum during task 2 followed by an increase during tasks 3 and 4 (p ≤ 0.020). During the initial tasks, the pupil size (p = 0.014) increased significantly. The results suggest that being repeatedly exposed to stressful tasks can produce in itself an escalation of psychological stress, this even prior to being exposed to the task. However, the characteristics of both the heart rate and pupil diameter were complex, thus, the findings highlight the importance of studying the effects and dynamics of different stress-generating factors. Monitoring heart rate was found useful to screen for stress responses, and thus, to be a vehicle for indication if and when rotation of deployed personnel is necessary to avoid sustained high stress exposures.
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  • Bertilsson, Johan, et al. (författare)
  • Towards systematic and objective evaluation of police officer performance in stressful situations
  • 2020
  • Ingår i: Police Practice and Research. - : Informa UK Limited. - 1561-4263 .- 1477-271X. ; 21:6, s. 655-669
  • Tidskriftsartikel (refereegranskat)abstract
    • To ensure a continuous high standard of police units, it is critical to recruit people who perform well in stressful situations. Today, this selection process includes performing a large series of tests, which still may not objectively reveal a person’s capacity to handle a life-threatening situation when subjected to high levels of stress. To obtain more systematic and objective data, 12 police officers were exposed to six scenarios with varying levels of threat while their heart rate and pupil size were monitored. The scenarios were filmed and six expert evaluators assessed the performance of the police officers according to seven predefined criteria. Four of the scenarios included addressing a moderate threat level task and the scenarios were executed in a rapid sequence. Two further scenarios included a familiar firearm drill performed during high and low threat situations. The results showed that there was a large agreement between the experts in how they judged the performance of the police officers (p < 0.001). Performance increased significantly over tasks in four of the seven evaluation criteria (p ≤ 0.037). There was also a significant effect of pupil size (p = 0.004), but not heart rate, when comparing the different sequential scenarios. Moreover, a high level of threat considerably impaired the motor performance of the police officers during the firearms drill (p = 0.002). Finally, the pupil seemed to systematically dilate more when a threat appeared immediately than with a delay in the scenarios (p = 0.007). We conclude that systematic and quantitative judgments from experts provide valuable and reliable information about the performance of participants in realistic and stressful policing scenarios. Furthermore, objective physiological measures of heart rate and pupil size may help to explain and understand why performance sometimes deteriorates.
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  • Bertilsson, J., et al. (författare)
  • Use of pepper spray in policing : retrospective study of situational characteristics and implications for violent situations
  • 2017
  • Ingår i: Police Practice & Research. - : Routledge. - 1561-4263 .- 1477-271X. ; 18:4, s. 391-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Pepper spray (OC) is a policing tool aimed to prevent or stop aggressive behavior by quickly and temporarily incapacitate without injuring. To date, few studies have investigated OC's operational usefulness and limitations. OC reduced violent behavior in 93% of the 936 incidents investigated. However, the operative range was often <2m and it took between 3 and 5 s of spraying before obtaining effect, partly owing to the difficulties of hitting a small, sometimes erratically moving target. Collateral hits were noted in 24% of the incidents, whereof 90% were other officers. Noteworthy, in 21% of incidents officers put themselves at large personal risk by using OC at close range against people armed with lethal weapons. Hence, OC emerges as a suitable tool for handling low threat situations but lacks key traits to ensure safe and efficient policing of high threat situations, e.g., handling armed assailants.
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  • Björklund, Martin, 1961- (författare)
  • Effects of repetitive work on proprioception and of stretching on sensory mechanisms : implications for work-related neuromuscular disorders
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aims of the thesis were (i) to investigate the impact of repetitive low-intensity work exposure on proprioception and (ii) to examine effects of muscle stretching (especially sensory effects and effects on muscle nociception) and to relate its application to the prevention, alleviation and/or treatment of work-related neuromuscular disorders. The effects of low-intensity repetitive work on the shoulder proprioception were tested in healthy subjects. The effect of working time on the retention of subjective fatigue and their relation to changes in proprioception, and the immediate effect of stretching on shoulder proprioception were investigated. A new method to test the stretchability of the rectus femoris muscle was investigated for reliability and validity and used to assess the effects of a two-week stretching regimen on range of motion and on subjective stretch sensation. Finally, the interactions between innocuous muscle stretch and nociceptive chemical stimulation on discharge behavior of nociceptive dorsal horn neurons in the feline spinal cord were explored. The main findings were as follows: 1) The repetitive low-intensity work to fatigue diminished the shoulder proprioception; the working time as well as the retention of subjective fatigue were partly related to the extent of changed proprioception. 2) There was no effect of acute muscle stretching on the proprioception. 3) The new method for testing muscle stretchability proved valid and reliable. A two-week stretching regimen increased the tolerance to stretch torque, but the range of motion remained unchanged. 4) Half of the nociceptive dorsal horn neurons that responded to close arterial injections of bradykinin were modulated by muscle stretching applied directly after the injections. Altogether, the results give credence to the hypothesis of an involvement of sensory information distortion due to repetitive low-intensity work exposure in the development of work-related neuromuscular disorders. Increased tolerance to stretch torque may be an important mechanism in explaining improvements following stretch treatment. The spinal interactions between innocuous stretch and nociceptive muscle afferent inputs indicate a possible mechanism involved in stretching-induced pain alleviation.
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  • Brantberg, K, et al. (författare)
  • Galvanically induced asymmetric optokinetic after-nystagmus
  • 1990
  • Ingår i: Acta Oto-Laryngologica. - 0001-6489. ; 110:3-4, s. 95-189
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of an asymmetric vestibular input on the symmetry of horizontal optokinetic after-nystagmus (OKAN) was studied in twenty healthy subjects. Optokinetic nystagmus (OKN) was elicited by a whole-field optokinetic drug, rotating at 90 degrees/s, and eye-movements were recorded by a DC electro-oculographic technique (EOG). The ratio of OKAN following right and left-beating OKN respectively was computed. An asymmetric vestibular input was generated by a continuous bi-polar, bi-aural galvanic stimulus (1 mA) to the vestibular nerves during the optokinetic stimulation and the recording of the OKAN. During galvanic stimulation the relation between left and right-beating OKAN was asymmetric, compared with the OKAN found after optokinetic stimulation only. The galvanic stimulus caused a preponderance for OKAN with the fast phase beating toward the cathode. Thus, the small vestibular asymmetry induced by the galvanic stimulus, which was not strong enough to produce nystagmus by itself, caused an asymmetric OKAN. These findings suggest that examination of OKAN may be of value to detect small vestibular asymmetries in peripheral vestibular disorders in man.
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  • Bringmann, Karl, et al. (författare)
  • Multivariate Analysis of Orthogonal Range Searching and Graph Distances
  • 2019
  • Ingår i: 13th International Symposium on Parameterized and Exact Computation, IPEC 2018 : August 20-24, 2018, Helsinki, Finland - August 20-24, 2018, Helsinki, Finland. - 9783959770842 ; 115, s. 1-13
  • Konferensbidrag (refereegranskat)abstract
    • We show that the eccentricities, diameter, radius, and Wiener index of an undirected n-vertex graph with nonnegative edge lengths can be computed in time O(n * binom{k+ceil[log n]}{k} * 2^k k^2 log n), where k is the treewidth of the graph. For every epsilon>0, this bound is n^{1+epsilon}exp O(k), which matches a hardness result of Abboud, Vassilevska Williams, and Wang (SODA 2015) and closes an open problem in the multivariate analysis of polynomial-time computation. To this end, we show that the analysis of an algorithm of Cabello and Knauer (Comp. Geom., 2009) in the regime of non-constant treewidth can be improved by revisiting the analysis of orthogonal range searching, improving bounds of the form log^d n to binom{d+ceil[log n]}{d}, as originally observed by Monier (J. Alg. 1980). We also investigate the parameterization by vertex cover number.
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  • Bringmann, Karl, et al. (författare)
  • Multivariate Analysis of Orthogonal Range Searching and Graph Distances
  • 2020
  • Ingår i: Algorithmica. - : Springer Science and Business Media LLC. - 0178-4617 .- 1432-0541. ; 82:8, s. 2292-2315
  • Tidskriftsartikel (refereegranskat)abstract
    • We show that the eccentricities, diameter, radius, and Wiener index of an undirected n-vertex graph with nonnegative edge lengths can be computed in time O(n·(k+⌈logn⌉k)·2klogn), where k is linear in the treewidth of the graph. For every ϵ> 0 , this bound is n1 + ϵexp O(k) , which matches a hardness result of Abboud et al. (in: Proceedings of the Twenty-Seventh Annual ACM-SIAM Symposium on Discrete Algorithms, 2016. https://doi.org/10.1137/1.9781611974331.ch28) and closes an open problem in the multivariate analysis of polynomial-time computation. To this end, we show that the analysis of an algorithm of Cabello and Knauer (Comput Geom 42:815–824, 2009. https://doi.org/10.1016/j.comgeo.2009.02.001) in the regime of non-constant treewidth can be improved by revisiting the analysis of orthogonal range searching, improving bounds of the form log dn to (d+⌈logn⌉d), as originally observed by Monier (J Algorithms 1:60–74, 1980. https://doi.org/10.1016/0196-6774(80)90005-X). We also investigate the parameterization by vertex cover number.
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18.
  • Cha, Yoon-Hee, et al. (författare)
  • Mal de débarquement syndrome : Diagnostic criteria consensus document of the classification committee of the bárány society
  • 2020
  • Ingår i: Journal of Vestibular Research: Equilibrium and Orientation. - 1878-6464. ; 30:5, s. 285-293
  • Tidskriftsartikel (refereegranskat)abstract
    • We present diagnostic criteria for mal de débarquement syndrome (MdDS) for inclusion into the International Classification of Vestibular Disorders. The criteria include the following: 1] Non-spinning vertigo characterized by an oscillatory sensation ('rocking,' 'bobbing,' or 'swaying,') present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours. MdDS may be designated as "in evolution," if symptoms are ongoing but the observation period has been less than 1 month; "transient," if symptoms resolve at or before 1 month and the observation period extends at least to the resolution point; or "persistent" if symptoms last for more than 1 month. Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety. Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed. Motion-moderated oscillatory vertigo can also occur without a motion trigger, typically following another vestibular disorder, a medical illness, heightened psychological stress, or metabolic disturbance. Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD. Further research is needed into its phenomenological and biological relationship to MdDS, PPPD, and other vestibular disorders.
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  • Cha, Yoon-Hee, et al. (författare)
  • Motion sickness diagnostic criteria : Consensus document of the classification committee of the Bárány society
  • 2021
  • Ingår i: Journal of Vestibular Research: Equilibrium and Orientation. - 1878-6464. ; 31:5, s. 327-344
  • Tidskriftsartikel (refereegranskat)abstract
    • We present diagnostic criteria for motion sickness, visually induced motion sickness (VIMS), motion sickness disorder (MSD), and VIMS disorder (VIMSD) to be included in the International Classification of Vestibular Disorders. Motion sickness and VIMS are normal physiological responses that can be elicited in almost all people, but susceptibility and severity can be high enough for the response to be considered a disorder in some cases. This report provides guidelines for evaluating signs and symptoms caused by physical motion or visual motion and for diagnosing an individual as having a response that is severe enough to constitute a disorder.The diagnostic criteria for motion sickness and VIMS include adverse reactions elicited during exposure to physical motion or visual motion leading to observable signs or symptoms of greater than minimal severity in the following domains: nausea and/or gastrointestinal disturbance, thermoregulatory disruption, alterations in arousal, dizziness and/or vertigo, headache and/or ocular strain. These signs/symptoms occur during the motion exposure, build as the exposure is prolonged, and eventually stop after the motion ends. Motion sickness disorder and VIMSD are diagnosed when recurrent episodes of motion sickness or VIMS are reliably triggered by the same or similar stimuli, severity does not significantly decrease after repeated exposure, and signs/symptoms lead to activity modification, avoidance behavior, or aversive emotional responses. Motion sickness/MSD and VIMS/VIMSD can occur separately or together. Severity of symptoms in reaction to physical motion or visual motion stimuli varies widely and can change within an individual due to aging, adaptation, and comorbid disorders. We discuss the main methods for measuring motion sickness symptoms, the situations conducive to motion sickness and VIMS, and the individual traits associated with increased susceptibility. These additional considerations will improve diagnosis by fostering accurate measurement and understanding of the situational and personal factors associated with MSD and VIMSD.
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  • Degerman, Eva, et al. (författare)
  • Endolymphatic hydrops induced by different mechanisms responds differentially to spironolactone : a rationale for understanding the diversity of treatment responses in hydropic inner ear disease
  • 2019
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 139:8, s. 685-691
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The exact pathophysiological mechanism(s) underlying endolymphatic hydrops (EH) remain elusive. We have previously shown that chronic administration of vasopressin and inhibitors of the cAMP/cGMP degrading enzymes (PDE3, PDE4, PDE5) results in the development of EH to mice. Aims/objectives: Evaluate the ability of spironolactone, an aldosterone antagonist, to prevent EH, when induced by different pathways. Material and methods: Mice were treated for 4 weeks with vasopressin, the PDE3 inhibitor cilostamide and the PDE4 inhibitor rolipram in the presence or absence of spironolactone. EH was assessed using high resolution 9.4T MRI. The expression of proteins in human saccule sensory epithelium was studied with immunohistochemistry. Results: Spironolactone prevents EH induced by vasopressin and rolipram, but not hydrops induced by cilostamide. The aldosterone target ENaC and the mineralocorticoid receptor were expressed in the human saccule sensory epithelium. Conclusions: The effect of spironolactone on EH appears to be pathway-dependent and may provide explanations why certain drugs may be effective in some patients with hydropic ear disease while not in others. Significance: Extrapolating this finding to the clinic supports that a personalized medicine approach is probably necessary in the treatment of diseases involving EH, as different pathways may be needed to be targeted for treatment.
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  • Degerman, Eva, et al. (författare)
  • Expression of insulin signalling components in the sensory epithelium of the human saccule.
  • 2013
  • Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 352:3, s. 469-478
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have demonstrated a link between diabetes and the dysfunction of the inner ear. Few studies, however, have reported the signalling mechanisms involved in metabolic control in human inner ear cells. Knowledge of the expression and role of the insulin receptor and downstream signalling components in the inner ear is sparce. Our immunohistochemistry approach has shown that the insulin receptor, insulin receptor substrate 1 (IRS1), protein kinase B (PKB) and insulin-sensitive glucose transporter (GLUT4) are expressed in the sensory epithelium of the human saccule, which also exhibits expression of a calcium-sensitive cAMP/cGMP phosphodiesterase 1C (PDE1C) and the vasopressin type 2 receptor. IRS1 and PDE1C are selectively expressed in sensory epithelial hair cells, whereas the other components are expressed in sensory epithelial supporting cells or in both cell types, as judged from co-expression or non-co-expression with glial fibrillary acidic protein, a marker for supporting cells. Furthermore, IRS1 appears to be localized in association with sensory nerves, whereas GLUT4 is expressed in the peri-nuclear area of stromal cells, as is the case for aquaporin 2. Thus, the insulin receptor, insulin signalling components and selected cAMP signalling components are expressed in the human saccule. In addition to well-known mechanisms of diabetes complications, such as neuropathy and vascular lesions, the expression of these proteins in the saccule could have a role in the observed link between diabetes and balance/hearing disorders.
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  • Degerman, Eva, et al. (författare)
  • Identification of new signaling components in the sensory epithelium of human saccule.
  • 2011
  • Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To locate components and target proteins of relevance for the cAMP and cGMP signaling networks including cAMP and cGMP phosphodiesterases (PDEs), salt-inducible kinases (SIKs), subunits of Na+, K+-ATPases, and aquaporins (AQPs) in the human saccule. Methods: The human saccule was dissected out during the removal of vestibular schwannoma via the translabyrinthine approach and immediately fixed. Immunohistochemistry was performed using PDE, SIK, Na(+), K(+)-ATPase, and AQP antibodies. Results: PDEs selective for cAMP (PDE4A, PDE4D, and PDE8A) and cGMP (PDE9A) as well a dual specificity PDE (PDE10A) were detected in the sensory epithelium of the saccule. Furthermore, AQP2, 4, and 9, SIK1 and the α-1 subunit of the Na(+), K(+)-ATPase were detected. Conclusion: cAMP and cGMP are important regulators of ion and water homeostasis in the inner ear. The identification of PDEs and SIK1 in the vestibular system offers new treatment targets for endolymphatic hydrops. Exactly how the PDEs are connected to SIK1 and the SIK1 substrate Na(+), K(+)-ATPase and to AQPs 2, 4, 9 remains to be elucidated. The dissection of the signaling networks utilizing these components and evaluating their roles will add new basic knowledge regarding inner ear physiology.
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23.
  • Degerman, Eva, et al. (författare)
  • Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI
  • 2017
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 137:1, s. 8-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Conclusion: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. Objective: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling. Method: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry. Results: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule.
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24.
  • Degerman, Eva, et al. (författare)
  • Vasopressin induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4 T MRI.
  • 2015
  • Ingår i: Hearing Research. - : Elsevier BV. - 0378-5955. ; 330:Part A, s. 119-124
  • Tidskriftsartikel (refereegranskat)abstract
    • From histopathological specimens, endolymphatic hydrops has been demonstrated in association with inner ear disorders. Recent studies have observed findings suggestive of hydrops using MRI in humans. Previous studies suggest that vasopressin may play a critical role in endolymph homeostasis and may be involved in the development of Ménière's disease. In this study we evaluate the effect of vasopressin administration in vivo in longitudinal studies using two mouse strains. High resolution MRI at 9.4 T in combination with intraperitoneally delivered Gadolinium contrast, was performed before and after chronic subcutaneous administration of vasopressin via mini-osmotic pumps in the same mouse. A development of endolymphatic hydrops over time could be demonstrated in C57BL6 mice (5 mice, 2 and 4 weeks of administration) as well as in CBA/J mice (4 mice, 2 weeks of administration; 6 mice, 3 and 4 weeks of administration). In most C57BL6 mice hydrops developed first after more than 2 weeks while CBA/J mice had an earlier response. These results may suggest an in vivo model for studying endolymphatic hydrops and corroborates the future use of MRI as a tool in the diagnosis and treatment of inner ear diseases, such as Ménière's disease. MRI may also be developed as a critical tool in evaluating inner ear homeostasis in genetically modified mice, to augment the understanding of human disease. This article is part of a Special Issue entitled .
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25.
  • Dumas, Georges, et al. (författare)
  • Clinical interest of postural and vestibulo-ocular reflex changes induced by cervical muscles and skull vibration in compensated unilateral vestibular lesion patients
  • 2013
  • Ingår i: Journal of Vestibular Research. - 1878-6464. ; 23:1, s. 41-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Skull vibration induces nystagmus in unilateral vestibular lesion (UVL) patients. Vibration of skull, posterior cervical muscles or inferior limb muscles alters posture in recent UVL patients. This study aimed to investigate the postural effect of vibration in chronic compensated UVL patients. Vibration was applied successively to vertex, each mastoid, each side of posterior cervical muscles and of triceps surae in 12 UVL patients and 9 healthy subjects. Eye movements were recorded with videonystagmography. Postural control was evaluated in eyes open (EO) and eyes closed (EC) conditions. Sway area, sway path, anteroposterior and medio-lateral sways were recorded. A vibration induced nystagmus (VIN) beating toward the healthy side was obtained for each UVL patient during mastoid vibration. In EO, only sway path was higher in UVL group during vibration of mastoids and posterior cervical muscles. The EO postural impairments of UVL patients could be related to the eye movements or VIN, leading to visual perturbations, or to a proprioceptive error signal, providing an erroneous representation of head position. The vibration-induced sway was too small to be clinically useful. Vestibulo-ocular reflex observed with videonystagmography during mastoid vibration seems more relevant to reveal chronic UVL than vestibulo-spinal reflex observed with posturography.
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