We examined the relationship between deactivation and inactivation in Kv4.2 channels. In particular, we were interested in the role of a Kv4.2 N-terminal domain and accessory subunits in controlling macroscopic gating kinetics and asked if the effects of N-terminal deletion and accessory subunit coexpression conform to a kinetic coupling of deactivation and inactivation. We expressed Kv4.2 wild-type channels and N-terminal deletion mutants in the absence and presence of Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-like proteins (DPPs) in human embryonic kidney 293 cells. Kv4.2-mediated A-type currents at positive and deactivation tail currents at negative membrane potentials were recorded under whole-cell voltage-clamp and analyzed by multi-exponential fitting. The observed changes in Kv4.2 macroscopic inactivation kinetics caused by N-terminal deletion, accessory subunit coexpression, or a combination of the two maneuvers were compared with respective changes in deactivation kinetics. Extensive correlation analyses indicated that modulatory effects on deactivation closely parallel respective effects on inactivation, including both onset and recovery kinetics. Searching for the structural determinants, which control deactivation and inactivation, we found that in a Kv4.2 Delta 2-10 N-terminal deletion mutant both the initial rapid phase of macroscopic inactivation and tail current deactivation were slowed. On the other hand, the intermediate and slow phase of A-type current decay, recovery from inactivation, and tail current decay kinetics were accelerated in Kv4.2 Delta 2-10 by KChIP2 and DPPX. Thus, a Kv4.2 N-terminal domain, which may control both inactivation and deactivation, is not necessary for active modulation of current kinetics by accessory subunits. Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs.

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Purpose The aim of this study was to assess the impact of arm position in computed tomography (CT) of the clavicle performed for forensic age estimation on clavicular position, image noise, and radiation dose. Methods and materials Forty-seven CT scans of the medial clavicular epiphysis performed for forensic age estimation were conducted with either hands and arms held upwards (CTHU, 28 persons) or positioned at the body (CTHD, 19 persons). Presets were identical for both positions (70 mAs/140 kVp; Brilliance iCT, Philips). Each CT scan was reconstructed with an iterative algorithm (i-Dose 4) and evaluated at the middle of the sternoclavicular joint. Clavicular angle was measured on a.p. topograms in relation to a horizontal line. Quantitative image noise was measured in air at the level of medial clavicular epiphysis. Effective dose and scan length were recorded. Results Hands-up position compared with hands-down position resulted in a lower lateral body diameter (CTHU 41.1 ± 3.6 cm vs. CTHD 44.6 ± 3.1 cm; P = 0.03), a reduced quantitative image noise (CTHU: 39.5 ± 9.2; CTHD: 46.2 ± 8.3; P = 0.02), and lower CTDIvol (5.1 ± 1.4 mGy vs. 6.7 ± 1.8 mGy; P = 0.001). Scan length was longer in patients examined with hands up (HU: 8.5 ± 3.4 cm; HD: 6.2 ± 2.1 cm; P = 0.006). Mean effective dose for CTHU was 0.79 ± 0.32 mSv compared with 0.95 ± 0.38 mSv in CTHD (P = 0.12). Clavicular angle was 17° ± 6° in patients with hands down and 32° ± 7° in patients with hands up (P < 0.001). Conclusion By elevated arm positioning, the image quality of clavicular CT scans can be improved while maintaining radiation dose compared with hands down. Clavicular position differs according to the hand position. Thus, positioning patients with elevated hands is advisable for forensic clavicular CT examinations, but multiplanar CT reconstructions should be adjusted to clavicular position and scan length should be reduced to a minimum.

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Hemispheric lateralization is a frequently encountered phenomenon of cortical function. It describes the functional specialization of a region on one side of the brain for a given task. It is well characterized in motor and sensory, as well as language systems and becomes more and more known for various cognitive domains. While in the adult healthy brain hemispheric lateralization is mostly set, pathological processes may lead to cortical reorganization. In these cases neuroplasticity of the corresponding region in the non-dominant hemisphere seems to play an important role. In a previous study we investigated language associated regions in right-handed patients with frontal and temporal tumors of the left hemisphere. We observed a marked change of language lateralization in these patients towards the non-dominant hemisphere as measured by functional MRI (Partovi et al., 2012).In the present study we evaluated activation and lateralization of cortical motor areas in patients with tumors of the central region. BOLD fMRI was performed during unilateral voluntary movements of the contralesional hand in 87 patients. Individual correlations of measured BOLD-signals with the model hemodynamic reference function were determined on a ROI basis in single subjects and compared to those of 16 healthy volunteers. In volunteers the strongest activation is usually found in the M1 hand representation contralateral to the movement, while a weaker homotopic co-activation is observed in ipsilateral M1 (Stippich et al., 2007a). In the patient group our results show significant changes of motor activations, ranging from a reduction of M1 lateralization to equalization of M1 activations or even inversion of M1 lateralization during contralesional movements. This study corroborates in a large patient group the idea that lesions affecting M1 may lead to functional reorganization of cortical motor systems and in particular equalize hemispheric lateralization. However, it is not yet clear whether these changes are only an epiphenomenon or indeed reflect an attempt of recovery of brain function.

Objective: 17-Hydroxyprogesterone (17-OHP) screening for classical congenital adrenal hyperplasia (CAH) is part of many newborn screening programs worldwide. Cut-off values are relatively high, and screening sensitivity does not reach 100%. Recently, the glucocorticoid receptor (GR) N363S-variant has been linked to relatively low degree of virilization and comparatively lower 17-OHP serum concentrations in clinically diagnosed female CAH patients. We sought to determine whether functional GR gene variants, either increasing (N363S, BclI) or decreasing GR sensitivity (R23K), underlie the variable 17-OHP screening levels in healthy newborns. Design: GR genotypes were compared with 17-OHP screening values in 1000 random samples from routine screening. 17-OHP was measured by conventional immunoassay (TRFIA) and a liquid chromatography-tandem mass spectrometry method (LC-MS/MS), which has been shown to increase screening specificity by steroid profiling and avoiding cross-reactions of the 17-OHP-antibody. Results: There was no significant association of 17-OHP with GR genotypes, even after inclusion of gestational and postnatal age as covariates. However, among LC-MS/MS steroid measurements, we observed some unexpected trends, including lower 11-deoxycortisol concentrations in both 363S-and 23K-carriers. For carriers of the frequent BclI variant, linear regression analysis revealed a significant increase of 4-androstenedione levels with every mutant allele inherited. Conclusions: Functional GR variants do not underlie the variation of 17-OHP values observed in healthy individuals. However, whether and to which extent genetically determined differences in individual GR sensitivity influence 17-OHP screening levels in conditions of a pathological hypothalamus-pituitary-adrenal gland-axis stimulation and thus may explain false-negative screening results in those affected by CAH remains to be investigated.

A 42-year-old man without known history of alcoholism presented comatose. CT and MRI (figure) demonstrated characteristic imaging features of Marchiafava-Bignami disease 1 without signs of Wernicke encephalopathy (such as involvement of the mammillary bodies). Under symptomatic treatment including artificial respiration and parenteral nutrition, the patient's Glasgow Coma Scale score improved from 3 to 7. Marchiafava-Bignami is a rare disease associated with alcoholism though rarely also seen in patients without alcoholism, 1 characterized by demyelination and necrosis of the corpus callosum. 2 Since clinical symptoms can vary from cognitive impairment, gait disturbance, and hemiparesis to stupor, coma, and death, early recognition of neuroimaging characteristics is crucial for diagnosis and treatment.

Clinically acceptable image quality of cervical spine CTs for evaluation of bony structures of cadaveric specimens with different body habitus can be achieved with a reference mAs of 105 at 120 kVp with iterative reconstruction. Pull-down of shoulders during acquisition could improve image quality but may not be feasible in trauma patients with unknown injuries.