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Background: Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity.
Methods: We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls.
Results: We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes.
Conclusions: A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology.
Die vorliegende Arbeit untersucht, ob mit zunehmendem Alter während der Mitose häufiger Geschlechtschromsomen verlorengehen. Die Beobachtungen erfolgten an Lymphozytenkulturen gesunder weiblicher und männlicher Probanden aus drei verschiedenen Altersgruppen. Unter Zugabe von 5-Azadeoxycytidin, einem Nukleosidanalogon, ergab sich in den höheren Altersgruppen ein verstärktes Auftreten von Mikronuklei. Mikronuklei enthalten Chromosomen oder -bruchstücke, die während der Mitose nicht in die Tochterzellkerne integriert wurden. Mittels in situ Hybridisierung konnte in den Mikronuklei der Frauen zu 5,5 Prozent ein X-Chromosom, bei den Männern mit 10,7 Prozent überzufällig häufig ein Y-Chromosom nachgewiesen werden. Zwischen den einzelnen Altersstufen änderte sich dieser Anteil nicht wesentlich. 5-Azadeoxycytidin wird als Nukleosidanalogon während der Replikation in die DNA eingebaut und verhindert die Methylierung des Tochterstrangs, da ein Kohlenstoffatom im Pyrimidinrings durch ein Stickstoffatom substituiert ist. Wahrscheinlich resultiert aus der Hyomethylierung eine falsche "Verpackung" des Gonosoms während der Mitose, dadurch erfolgt eine fehlerhafte Aufteilung des Chromosoms mit Bildung eines Mikronukleus.
Die vorliegende Arbeit untersucht, ob mit zunehmendem Alter während der Mitose häufiger Geschlechtschromsomen verlorengehen. Die Beobachtungen erfolgten an Lymphozytenkulturen gesunder weiblicher und männlicher Probanden aus drei verschiedenen Altersgruppen. Unter Zugabe von 5-Azadeoxycytidin, einem Nukleosidanalogon, ergab sich in den höheren Altersgruppen ein verstärktes Auftreten von Mikronuklei. Mikronuklei enthalten Chromosomen oder -bruchstücke, die während der Mitose nicht in die Tochterzellkerne integriert wurden. Mittels in situ Hybridisierung konnte in den Mikronuklei der Frauen zu 5,5 Prozent ein X-Chromosom, bei den Männern mit 10,7 Prozent überzufällig häufig ein Y-Chromosom nachgewiesen werden. Zwischen den einzelnen Altersstufen änderte sich dieser Anteil nicht wesentlich. 5-Azadeoxycytidin wird als Nukleosidanalogon während der Replikation in die DNA eingebaut und verhindert die Methylierung des Tochterstrangs, da ein Kohlenstoffatom im Pyrimidinrings durch ein Stickstoffatom substituiert ist. Wahrscheinlich resultiert aus der Hyomethylierung eine falsche "Verpackung" des Gonosoms während der Mitose, dadurch erfolgt eine fehlerhafte Aufteilung des Chromosoms mit Bildung eines Mikronukleus.
Background:
Fatty Degeneration (FD) of the rotator cuff muscles influences functional and anatomical outcome after rotator cuff repair. The MRI based estimation of fatty degeneration is the gold standard. There is some evidence that Ultrasound elastography (EUS) can detect local differences of tissue stiffness in muscles and tendons. Shear-wave elastography (SWE) was evaluated to determine the extent to which shear wave velocity was associated with measures of fatty degeneration. MRI-spectroscopic fat measurement was used as a reference to quantify the amount of fat in the muscle belly.
Methods:
Forty-two patients underwent SWE of the supraspinatus muscles at its thickest diameter. After ultrasound evaluation an MRI-spectroscopic fat measurement of the supraspinatus muscle was performed using the SPLASH-technique. A gel filled capsule was used to locate the measured area in the MRI. The values of shear wave velocity (SWV) measured with SWE and spectroscopic fat measurement were correlated statistically using Pearson’s correlation test.
Results:
Correlation of the fat amount measured with MRI-spectroscopy and the SWV measured with SWE was ρ =0.82. Spectroscopic measured fat ratio of the supraspinatus muscle ranged from 0% to 77.41% and SWV from 1.59 m/s to 5.32 m/s. In 4 patients no sufficient SWE could be performed, these individuals showed a larger diameter of the overlying soft tissue. SWV measured with SWE showed a good correlation with MRI spectroscopic fat amount of the supraspinatus muscle.
Conclusion:
These preliminary data suggest that SWE may be a sufficient tool in detecting and estimating the amount of fatty degeneration in the supraspinatus muscle in real time. Large overlying soft tissue may be a limitation in performing sufficient EUS.
NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells
(2016)
Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.
Background
Skeletal muscle function dysfunction has been reported in patients with cystic fibrosis (CF). Studies so far showed inconclusive data whether reduced exercise capacity is related to intrinsic muscle dysfunction in CF.
Methods
Twenty patients with CF and 23 age-matched controls completed an incremental cardiopulmonary cycling test. Further, a Wingate anaerobic test to assess muscle power was performed. In addition, all participants completed an incremental knee-extension test with 31P magnetic resonance spectroscopy to assess muscle metabolism (inorganic phosphate (Pi) and phosphocreatinine (PCr) as well as intracellular pH). In the MRI, muscle cross-sectional area of the M. quadriceps (qCSA) was also measured. A subgroup of 15 participants (5 CF, 10 control) additionally completed a continuous high-intensity, high-frequency knee-extension exercise task during 31P magnetic resonance spectroscopy to assess muscle metabolism.
Results
Patients with CF showed a reduced exercise capacity in the incremental cardiopulmonary cycling test (VO2peak: CF 77.8 ± 16.2%predicted (36.5 ± 7.4 ml/qCSA/min), control 100.6 ± 18.8%predicted (49.1 ± 11.4 ml/qCSA/min); p < 0.001), and deficits in anaerobic capacity reflected by the Wingate test (peak power: CF 537 ± 180 W, control 727 ± 186 W; mean power: CF 378 ± 127 W, control 486 ± 126 W; power drop CF 12 ± 5 W, control 8 ± 4 W. all: p < 0.001). In the knee-extension task, patients with CF achieved a significantly lower workload (p < 0.05). However, in a linear model analysing maximal work load of the incremental knee-extension task and results of the Wingate test, respectively, only muscle size and height, but not disease status (CF or not) contributed to explaining variance. In line with this finding, no differences were found in muscle metabolism reflected by intracellular pH and the ratio of Pi/PCr at submaximal stages and peak exercise measured through MRI spectroscopy.
Conclusions
The lower absolute muscle power in patients with CF compared to controls is exclusively explained by the reduced muscle size in this study. No evidence was found for an intrinsic skeletal muscle dysfunction due to primary alterations of muscle metabolism.