| 1. |
- Abdel-Khalik, Jonas, et al.
(författare)
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Bile acid biosynthesis in Smith-Lemli-Opitz syndrome bypassing cholesterol: Potential importance of pathway intermediates.
- 2021
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Ingår i: The Journal of steroid biochemistry and molecular biology. - : Elsevier BV. - 1879-1220 .- 0960-0760. ; 206
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids are the end products of cholesterol metabolism secreted into bile. They are essential for the absorption of lipids and lipid soluble compounds from the intestine. Here we have identified a series of unusual Δ5-unsaturated bile acids in plasma and urine of patients with Smith-Lemli-Opitz syndrome (SLOS), a defect in cholesterol biosynthesis resulting in elevated levels of 7-dehydrocholesterol (7-DHC), an immediate precursor of cholesterol. Using liquid chromatography - mass spectrometry (LC-MS) we have uncovered a pathway of bile acid biosynthesis in SLOS avoiding cholesterol starting with 7-DHC and proceeding through 7-oxo and 7β-hydroxy intermediates. This pathway also occurs to a minor extent in healthy humans, but elevated levels of pathway intermediates could be responsible for some of the features SLOS. The pathway is also active in SLOS affected pregnancies as revealed by analysis of amniotic fluid. Importantly, intermediates in the pathway, 25-hydroxy-7-oxocholesterol, (25R)26-hydroxy-7-oxocholesterol, 3β-hydroxy-7-oxocholest-5-en-(25R)26-oic acid and the analogous 7β-hydroxysterols are modulators of the activity of Smoothened (Smo), an oncoprotein that mediates Hedgehog (Hh) signalling across membranes during embryogenesis and in the regeneration of postembryonic tissue. Computational docking of the 7-oxo and 7β-hydroxy compounds to the extracellular cysteine rich domain of Smo reveals that they bind in the same groove as both 20S-hydroxycholesterol and cholesterol, known activators of the Hh pathway.
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| 2. |
- Boscato, Noeli, et al.
(författare)
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Impact of oral motor task training on corticomotor pathways and diadochokinetic rates in young healthy participants
- 2022
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842 .- 0305-182X. ; 49:9, s. 924-934
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Tidskriftsartikel (refereegranskat)abstract
- Background Studies addressing the training-induced neuroplasticity and interrelationships of the lip, masseter, and tongue motor representations in the human motor cortex using single syllable repetition are lacking. Objective This study investigated the impact of a repeated training in a novel PaTaKa diadochokinetic (DDK) orofacial motor task (OMT) on corticomotor control of the lips, masseter, and tongue muscles in young healthy participants. Methods A total of 22 young healthy volunteers performed 3 consecutive days of training in an OMT. Transcranial magnetic stimulation was applied to elicit motor evoked potentials (MEPs) from the lip, masseter, tongue, and first dorsal interosseous (FDI, internal control) muscles. MEPs were assessed by stimulus-response curves and corticomotor mapping at baseline and after OMT. The DDK rate from PaTaKa single syllable repetition and numeric rating scale (NRS) scores were also obtained at baseline and immediately after each OMT. Repeated-measures analysis of variance was used to detect differences at a significance level of 5%. Results There was a significant effect of OMT and stimulus intensity on the lips, masseter, and tongue MEPs compared to baseline (p < .001), but not FDI MEPs (p > .05). OMT increased corticomotor topographic maps area (p < .001), and DDK rates (p < .01). Conclusion Our findings suggest that 3 consecutive days of a repeated PaTaKa training in an OMT can induce neuroplastic changes in the corticomotor pathways of orofacial muscles, and it may be related to mechanisms underlying the improvement of orofacial fine motor skills due to short-term training. The clinical utility should now be investigated.
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| 3. |
- Hayakawa, Hidetoshi, et al.
(författare)
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Drop homotopic effects of masseter-muscle pain on somatosensory sensitivity in healthy participants
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Current pain classifications use 1.0-kg palpation of the masseter muscle to distinguish between "pain patients" and "healthy controls" but a thorough understanding of the normal physiological responses to various somatosensory stimuli is lacking. The aim of this study was to investigate somatosensory function of the skin over the masseter muscle in healthy participants that were divided into a masseter pain prone group (MPP) (n = 22) and non-MPP group (n = 22), according to the response to a 1.0-kg palpation. Quantitative sensory testing (QST) was performed at the skin above the right masseter muscle (homotopic). In an additional experiment, 13 individuals each from MPP and non-MPP received application of 60% topical lidocaine tape to the skin over the masseter muscle for 30 min. Immediately after, mechanical pain sensitivity (MPS), dynamic mechanical allodynia, and pressure pain threshold were tested. Homotopic MPS was significantly higher and PPTs significantly lower in MPP than in N-MPP (P < 0.05). Strikingly, no other differences in QST outcomes were observed between the groups (P > 0.05). After lidocaine application, no significant differences in homotopic MPS were observed between groups. The presence or absence of acute provoked pain in masseter muscle is exclusively associated with differences in homotopic MPS which is decreased following topical anesthesia.
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| 4. |
- Iida, Takashi, et al.
(författare)
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Plasticity in corticomotor pathways linked to a jaw protrusion training task : Potential implications for management of patients with obstructive sleep apnea.
- 2020
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1749
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the effect of a repeated and standardized jaw protrusion training (JPT) task on corticomotor excitability as assessed by motor evoked potentials (MEPs) in masseter and tongue muscle with the use of transcranial magnetic stimulation (TMS). Sixteen healthy participants performed three series of a standardized JPT task on three consecutive days. Each day participants performed 41-min of JPT consisting of three series. In all series, participants were instructed to target 50% and 100% of the maximum jaw protrusion positions. In the first and third series without any feedback but during the second series, participants were provided a custom-made mandibular advancement device to help achieve the correct protruded position. Single pulse TMS was applied to elicit MEPs from right masseter, right tongue and right first dorsal interosseous muscles (FDI) (as control), pre and post-task on Day-1 and -3. Masseter MEPs and tongue MEPs were significantly dependent on stimulus intensity (P < 0.001) and on task session (P < 0.001). Amplitude of masseter and tongue MEPs at post-task Day-3 were significantly higher compared to baseline values (pre-task Day-1) (P < 0.005). FDI MEPs were dependent on stimulus intensity only (P < 0.001) but not on task session (P = 0.677). Our novel findings suggest that participants performing an active and repeated JPT task demonstrate neuroplasticity in terms of increased corticomotor excitability not only in masseter muscles but also in tongue muscles. This finding may have implications for patients with obstructive sleep apnea treated by a mandibular advancement device where the lower jaw is passively held in a protruded position.
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| 5. |
- Ishii, Yuki, et al.
(författare)
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Comparison of masticatory muscle activity between young adults and elderly participants using a novel standardized bite device.
- 2024
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Ingår i: Journal of Dentistry. - : Elsevier. - 0300-5712 .- 1879-176X. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Standardized bite training is required to prevent oral hypofunction in elderly individuals. We aimed to compare masticatory muscle activity between 24 young adults and 16 pre-elderly individuals during a biting task using a novel standardized bite device (BD).METHODS: The BD was made of silicone rubber and included a high-force or low-force plate spring or no plate spring (dummy). The compressive stiffness of the material in each BD was measured using a texture analyzer. All participants performed a biting task 50-times at a rate of 1/s each using the three types of BDs on the right first molar. Electromyographic (EMG) activity was recorded bilaterally from the masseter and temporalis muscles. The variability of each biting training session was calculated as the coefficient of variance (CV) from the EMG activity during each biting task for each muscle. Masticatory muscle fatigue was assessed using a numerical rating scale (NRS).RESULTS: Compressive stiffness was significantly different between each BD (P < 0.001). The CV and NRS scores were not significantly different between the groups. The EMG activities during each bite task in all muscles were not significantly different for any measurement item between the age groups. The EMG activities of high- and low-force BDs in the right temporalis (ipsilateral) muscle were significantly higher than those of the dummy BD (P < 0.001).CONCLUSIONS: Compressive stiffness of the BD affected EMG activity only in the ipsilateral temporalis muscle, but not in the masseter or contralateral temporalis muscles, without any age effect.
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| 6. |
- Iwata, Yoshihiro, et al.
(författare)
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Effect of clinical experience and training with visual feedback on standardized palpation outcomes : Potential implications for assessment of jaw muscle sensitivity
- 2024
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Ingår i: Journal of Oral Rehabilitation. - : John Wiley & Sons. - 1365-2842. ; 51:3, s. 601-610
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evaluation of muscle pain and sensitivity by manual palpation is an important part of the clinical examination in patients with myalgia. However, the effects of clinical experience and visual feedback on palpation of the masticatory muscles with or without a palpometer are not known.Objective: To estimate the effects of clinical experience and visual feedback on the accuracy of palpation in standardized settings.Methods: Thirty-two dentists (age 35 ± 11 years) classified as either specialists (n = 16) or generalists (n = 16) participated in this experiment. All dentists were instructed to target force levels of 500- or 1000-gf, as determined on an electronic scale using either standardized palpometers or manual palpation (MP). All dentists participated in four different tests: MP, MP with visual feedback (MPVF), palpometer (PAL) and PAL with visual feedback (PALVF). Actual force values for each type of palpation from 0 to 2, 2 to 5 and 0 to 5 s were analysed by calculating target force level.Results: The relative differences during 2-5 and 0-5 s with 1000 gf were significantly lower for generalists than for specialists (p < .05). In generalists and specialists, the coefficients of variation and the relative differences during 2-5 s were significantly lower for PAL and PALVF than for MP (p < .05).Conclusions: These findings suggest that the use of a palpometer, but not clinical experience with palpation of masticatory muscles, increases the accuracy of palpation, and ≥2 s of palpation with a palpometer is optimal for masticatory muscles.
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| 7. |
- Masuda, Manabu, et al.
(författare)
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Standardized palpation of the temporalis muscle evoke referred pain and sensations in individuals without TMD
- 2022
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Ingår i: Clinical Oral Investigations. - : Springer. - 1432-6981 .- 1436-3771. ; 26, s. 1241-1249
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study aimed to determine if standardized palpations of the temporalis muscle evoke referred pain and/or sensations in individuals without TMD. Materials and methods This was a randomized, single-blinded study. The mechanical sensitivity of the right temporalis muscle was assessed in 32 participants without TMD with nine different stimulations to 15 test sites using palpometers (different stimulus intensities (0.5, 1.0, and 2.0 kg) and durations (2, 5, and 10 s). After each stimulus, participants were asked to score perceived pain intensity and intensity of unpleasantness on a 0-100 numeric rating scale as an indicator of mechanical sensitivity in the temporalis muscle and to indicate any areas of referred pain/sensations on a body chart. Results Pain intensity significantly differed between palpation durations, intensities, and test sites (P < 0.001). In contrast, unpleasantness significantly differed between palparation duration and intensities (P < 0.001), but not test sites. Participants more frequently reported referred pain/sensations evoked by the 10-s (34.4%) as opposed to the 2-s (6.3%) and 5-s (15.6%) palpation duration at the 2.0-kg stimulus intensity (P < 0.05). Conclusions Our present results indicate that referred pain/sensations in the orofacial region can be evoked by standardized palpation of the temporalis muscle and influenced by the palpation duration in individuals without TMD.
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| 8. |
- Matsuzaki, Satoshi, et al.
(författare)
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Effect of mandibular advancement device on plasticity in corticomotor control of tongue and jaw muscles
- 2021
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Ingår i: Journal of Clinical Sleep Medicine (JCSM). - : American Academy of Sleep Medicine. - 1550-9389 .- 1550-9397. ; 17:9, s. 1805-1813
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVES: This study aims to investigate if the use of a mandibular advancement device (MAD) is associated with neuroplasticity in corticomotor control of tongue and jaw muscles.METHODS: Eighteen healthy individuals participated in a randomized crossover study with 3 conditions for 2 weeks each: baseline, wearing an oral appliance (OA: sham MAD) or MAD during sleep. The custom-made MAD was constructed by positioning the mandible to 50% of its maximal protrusion limit. Transcranial magnetic stimulation (TMS) was applied to elicit motor evoked potentials (MEPs). The MEPs were assessed by constructing stimulus-response curves at four stimulus intensities: 90%, 100%, 120%, and 160% of the motor threshold (MT) from the right tongue and right masseter, and the first dorsal interosseous muscles (FDI, control) at baseline, after the first and the second intervention.RESULTS: There was a significant effect of condition and stimulus intensity both on the tongue and as well as on masseter MEPs (P < 0.01). Tongue and masseter MEPs were significantly higher at 120% and 160% following the MAD compared to the OA (P < 0.05). There were no effects of condition on FDI MEPs (P = 0.855).CONCLUSIONS: The finding suggests that MAD induces neuroplasticity in the corticomotor pathway of the tongue and jaw muscles associated with the new jaw position. Further investigations are required in patients with obstructive sleep apnea (OSA) to see if this cortical neuroplasticity may contribute or perhaps predict treatment effects with MADs in OSA.
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| 9. |
- Sigurdsson, Valgardur, et al.
(författare)
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Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver.
- 2016
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 18:4, s. 32-522
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Tidskriftsartikel (refereegranskat)abstract
- During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) before settling in the adult bone marrow. We recently reported that proliferating adult HSCs are vulnerable to ER stress caused by accumulation of mis-folded proteins. Here, we find that FL-HSCs, despite an increased protein synthesis rate and a requirement for protein folding, do not upregulate ER chaperones. Instead, bile acids (BAs), secreted from maternal and fetal liver, coordinate to serve as chemical chaperones. Taurocholic acid, the major BA in FL, supports growth of HSCs in vitro by inhibiting protein aggregation. In vivo, reducing BA levels leads to ER stress elevation and accumulation of aggregated proteins and significantly decreases the number of FL-HSCs. Taken together, these findings reveal that BA alleviation of ER stress is a mechanism required for HSC expansion during fetal hematopoiesis.
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