Collimation by a polycapillary half lens at 277 eV.

We report on the efficient collimation of soft X-rays with an energy of 277 eV by a halved polycapillary lens (PCL), made of borosilicate glass. Using electron-excited, micro fluorescence emission in the focus of the PCL, experiments reveal an angular divergence of (6.9 ± 0.2) mrad in the far field of the emitted beam. For a source of ≈5µm in size, that result is confirmed by simulations, obtained with a newly developed ray tracing code. An analytical fit model is proposed and applied to characterize the evolution of the measured as well as calculated, three-dimensional (3-D) intensity distribution. The photon flux density in a free-space propagation distance of (0.4 - 0.9) m from the PCL is enhanced by a factor of ≈(30 - 90) in comparison to the direct, not collimated radiation, as it is detected through a mm-sized transmission slit. Our findings could help to establish the halved PCL as a versatile tool in the table-top metrology of optical elements, such as mirrors and gratings for soft X-rays.

Highly efficient soft x-ray spectrometer for transient absorption spectroscopy with broadband table-top high harmonic sources.

We present a novel soft x-ray spectrometer for ultrafast absorption spectroscopy utilizing table-top femtosecond high-order harmonic sources. Where most commercially available spectrometers rely on spherical variable line space gratings with a typical efficiency on the order of 3% in the first diffractive order, this spectrometer, based on a Hettrick-Underwood design, includes a reflective zone plate as a dispersive element. An improved efficiency of 12% at the N K-edge is achieved, accompanied by a resolving power of 890. The high performance of the soft x-ray spectrometer is further demonstrated by comparing nitrogen K-edge absorption spectra from calcium nitrate in aqueous solution obtained with our high-order harmonic source to previous measurements performed at the electron storage ring facility BESSY II.

Bilateral Basal Ganglion Hemorrhage after Severe Olanzapine Intoxication.

Olanzapine is a second-generation antipsychotic drug which is generally considered safe with well therapeutic antipsychotic effects. We describe a patient suffering from bilateral intracerebral hemorrhage after severe olanzapine intoxication without underlying thrombocytopenia, arterial hypertension, or vascular malformation as cause of intracerebral hemorrhage. This raises the possibility of a direct side effect of high-dose olanzapine intake. So far, intracranial hemorrhage after olanzapine intoxication in such constellation has not been reported before. Given the high number of its prescription rates, our finding of intracranial hemorrhage after olanzapine intoxication is of high clinical relevance.

A support programme for secondary prevention in patients with transient ischaemic attack and minor stroke (INSPiRE-TMS): an open-label, randomised controlled trial.

BACKGROUND: Patients with recent stroke or transient ischaemic attack are at high risk for a further vascular event, possibly leading to permanent disability or death. Although evidence-based treatments for secondary prevention are available, many patients do not achieve recommended behavioural modifications and pharmaceutical prevention targets in the long-term. We aimed to investigate whether a support programme for enhanced secondary prevention can reduce the frequency of recurrent vascular events. METHODS: INSPiRE-TMS was an open-label, multicentre, international randomised controlled trial done at seven German hospitals with acute stroke units and a Danish stroke centre. Patients with non-disabling stroke or transient ischaemic attack within 2 weeks from study enrolment and at least one modifiable risk factor (ie, arterial hypertension, diabetes, atrial fibrillation, or smoking) were included. Computerised randomisation was used to allocate patients (1:1) either to the support programme in addition to conventional care or to conventional care alone. The support programme used feedback and motivational interviewing strategies with eight outpatient visits over 2 years aiming to improve adherence to secondary prevention targets. The primary outcome was the composite of major vascular events consisting of stroke, acute coronary syndrome, and vascular death, assessed in the intention-to-treat population (all patients who underwent randomisation, did not withdraw study participation, and had at least one follow-up). Outcomes were assessed at annual follow-ups using time-to-first-event analysis. All-cause death was monitored as a safety outcome. This trial is registered with ClinicalTrials.gov, NCT01586702. FINDINGS: From Aug 22, 2011, to Oct 30, 2017, we enrolled 2098 patients. Of those, 1048 (50·0%) were randomly assigned to the support programme group and 1050 (50·0%) patients were assigned to the conventional care group. 1030 (98·3%) patients in the support group and 1042 (99·2%) patients in the conventional care group were included in the intention-to-treat analysis. The mean age of analysed participants was 67·4 years and 700 (34%) were women. After a mean follow-up of 3·6 years, the primary outcome of major vascular events had occurred in 163 (15·8%) of 1030 patients of the support programme group and in 175 (16·8%) of 1042 patients of the conventional care group (hazard ratio [HR] 0·92, 95% CI 0·75-1·14). Total major vascular event numbers were 209 for the support programme group and 225 for the conventional care group (incidence rate ratio 0·93, 95% CI 0·77-1·12; p=0·46) and all-cause death occurred in 73 (7·1%) patients in the support programme group and 85 (8·2%) patients in the conventional care group (HR 0·85, 0·62-1·17). More patients in the support programme group achieved secondary prevention targets (eg, in 1-year-follow-up 52% vs 42% [p<0·0001] for blood pressure, 62% vs 54% [p=0·0010] for LDL, 33% vs 19% [p<0·0001] for physical activity, and 51% vs 34% [p=0·0010] for smoking cessation). INTERPRETATION: Provision of an intensified secondary prevention programme in patients with non-disabling stroke or transient ischaemic attack was associated with improved achievement of secondary prevention targets but did not lead to a significantly lower rate of major vascular events. Further research is needed to investigate the effects of support programmes in selected patients who do not achieve secondary prevention targets soon after discharge. FUNDING: German Federal Ministry of Education and Research, Pfizer, and German Stroke Foundation.

Automated Calculation of the Alberta Stroke Program Early CT Score: Feasibility and Reliability.

Background The Alberta Stroke Program Early CT Score (ASPECTS) evaluation is a qualitative method to evaluate focal hypoattenuation at brain CT in early acute stroke. However, interobserver agreement is only moderate. Purpose To compare ASPECTS calculated by using an automatic software tool to neuroradiologist evaluation in the setting of acute stroke. Materials and Methods For this retrospective study, consensus ASPECTS were defined by two neuroradiologists based on baseline noncontrast CTs collected from January 2017 to December 2017 from patients with an occlusion in the middle cerebral artery and from an additional cohort of patients suspected of having stroke and no large vessel occlusion. Imaging data from both baseline and follow-up CT was evaluated for the consensus reading. After 6 weeks, the same two neuroradiologists again determined ASPECTS by using only the baseline CT. For comparison, ASPECTS was also calculated from baseline CT images by using a commercially available software (RAPID ASPECTS). Both methods were compared by using weighted κ statistics. Results CT scans from 100 patients with middle cerebral artery occlusion (44 women [mean age ± standard deviation, 75 years ± 14] and 56 men [mean age, 71 years ± 14]) and 52 patients suspected of having stroke and no large vessel occlusion (19 women [mean age, 69 years ± 18] and 33 men [68 years ± 15]) were evaluated. Neuroradiologists showed moderate agreement with the consensus score (κ = 0.57 and κ = 0.56). Software analysis showed substantial agreement (κ = 0.9) with the consensus score. Software analysis showed a substantial agreement (κ = 0.78) after greater than 1 hour between symptom onset and imaging, which increased to high agreement (κ = 0.92) in the time window greater than 4 hours. The neuroradiologist raters did not achieve comparable results to the software until the time interval of greater than 4 hours (κ = 0.83 and κ = 0.76). Conclusion In acute stroke of the middle cerebral artery, the Alberta Stroke Program Early CT score calculated with automated software had better agreement than that of human readers with a predefined consensus score. © RSNA, 2019 Online supplemental material is available for this article.

Influence of the initial level of consciousness on early, goal-directed mobilization: a post hoc analysis.

PURPOSE: Early mobilization within 72 h of intensive care unit (ICU) admission improves functional status at hospital discharge. We aimed to assess the effectiveness of early, goal-directed mobilization in critically ill patients across a broad spectrum of initial consciousness levels. METHODS: Post hoc analysis of the international, randomized, controlled, outcome-assessor blinded SOMS trial conducted 2011-2015. Randomization was stratified according to the immediate post-injury Glasgow Coma Scale (GCS) (≤ 8 or > 8). Patients received either SOMS-guided mobility treatment with a facilitator or standard care. We used general linear models to test the hypothesis that immediate post-randomization GCS modulates the intervention effects on functional independence at hospital discharge. RESULTS: Two hundred patients were included in the intention-to-treat analysis. The significant effect of early, goal-directed mobilization was consistent across levels of GCS without evidence of effect modification, for the primary outcome functional independence at hospital discharge (p = 0.53 for interaction), as well as average achieved mobility level during ICU stay (mean achieved SOMS level) and functional status at hospital discharge measured with the functional independence measure. In patients with low GCS, delay to first mobilization therapy was longer (0.7 ± 0.2 days vs. 0.2 ± 0.1 days, p = 0.008), but early, goal-directed mobilization compared with standard care significantly increased functional independence at hospital discharge in this subgroup of patients with immediate post-randomization GCS ≤ 8 (OR 3.67; 95% CI 1.02-13.14; p = 0.046). CONCLUSION: This post hoc analysis of a randomized controlled trial suggests that early, goal-directed mobilization in patients with an impaired initial conscious state (GCS ≤ 8) is not harmful but effective.

Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study.

BACKGROUND: Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. AIM: The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. METHODS: 1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0.05). RESULTS: A total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68.2 ±â€¯7.6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0.001), and a worse performance in some of the cognitive subdomain scores (p < 0.05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants' total lesion burden (p < 0.05), no focal WMH locations were found to be associated with cognitive impairment. CONCLUSION: Age, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults.

Neurosonography After Mechanical Thrombectomy for Acute Stroke Treatment.

BACKGROUND AND PURPOSE: Mechanical thrombectomy has been shown to be effective for acute stroke treatment, but lesions of cerebral vessels can develop thereafter. Such lesions of recanalized vessels and altered cerebral hemodynamics after mechanical thrombectomy are poorly investigated. In particular for neurosonography, data are sparse. We aimed to describe hemodynamic changes and incidence of de-novo stenosis after mechanical thrombectomy with neurosonography. METHODS: Retrospective analysis of patients after successful mechanical thrombectomy for acute stroke therapy who received one neurosonography at baseline and during follow up. Peak systolic velocity (PSV) of all intracranial recanalized and reference vessels was extracted for analysis. Patients with an isolated increase or decrease of PSV (50% or 50 cm/second for anterior and 30% or 30 cm/second for posterior circulation) were identified and characterized. RESULTS: Eighty-eight patients (mean age 64.4; 34.1% female) were included in this study. In 9 (10.2%) patients, the vessel occlusion was located in the posterior, and in 79 (89.9%) patients the vessel occlusion was located in the anterior circulation. With predominance to the recanalized vessel, mean PSV decreased at both, the recanalized and the reference vessel during follow up. In 3 (3.4%) patients, an isolated increase of PSV was observed in the recanalized vessel, and in 6 (6.8%) patients an isolated decrease of PSV was observed in the recanalized vessel. CONCLUSION: Sonographic incidence of de-novo stenosis following mechanical thrombectomy seems to be low, in line with prior angiographic studies. However, as measured by neurosonography, cerebral hemodynamic in the recanalized vessel is dynamic after thrombectomy. This result is of interest for further prospective analysis.

Cortical abnormalities in episodic migraine: A multi-center 3T MRI study.

BACKGROUND: Several previous studies have investigated cortical abnormalities, specifically cortical thickness, in patients with migraine, with variable results. The relatively small sample sizes of most previous studies may partially explain these inconsistencies. OBJECTIVE: To investigate differences of cortical thickness between control subjects and migraineurs in a large cohort. METHODS: Three Tesla MRI data of 131 patients (38 with and 93 without aura) and 115 control subjects were analysed. A vertex-wise linear model was applied controlling for age, gender and MRI scanner to investigate differences between groups and determine the impact of clinical factors on cortical thickness measures. RESULTS: Migraineurs showed areas of thinned cortex compared with controls bilaterally in the central sulcus, in the left middle-frontal gyrus, in left visual cortices and the right occipito-temporal gyrus. Frequency of migraine attacks and the duration of the disorder had a significant impact on cortical thickness in the sensorimotor cortex and middle-frontal gyrus. Patients without aura showed thinner cortex than controls bilaterally in the central sulcus and in the middle frontal gyrus, in the left primary visual cortices, in the left supramarginal gyrus and in the right cuneus. Patients with aura showed clusters of thinner cortex bilaterally in the subparietal sulcus (between the precuneus and posterior cingulate cortex), in the left intraparietal sulcus and in the right anterior cingulate. CONCLUSION: These results indicate cortical abnormalities in specific brain regions in migraineurs. Some of the observed abnormalities may reflect a genetic susceptibility towards developing migraine attacks, while others are probably a consequence of repeated head pain attacks.

Association of clinical headache features with stroke location: An MRI voxel-based symptom lesion mapping study.

Background We have recently shown that the presence of headache in ischemic stroke is associated with lesions of the insular cortex. The aim of this post-hoc subgroup analysis was to investigate the association of specific headache features with stroke location in patients with acute ischemic stroke. Methods In this observational study, patients (mean age: 61.5, 58% males) with ischemic stroke and acute headache (n = 49) were investigated. Infarcts were manually outlined on 3D diffusion weighted magnetic resonance imaging (MRI) scans and transformed into standard stereotaxic space; lesions of the left hemisphere were mirrored in the x-axis to allow a voxel-wise group analysis of all patients. We analyzed the association of lesion location and the following phenotypical characteristics by voxel-based symptom lesion mapping: Headache intensity, different qualities of headache (pulsating, tension-type like and stabbing), and the presence of nausea, of cranial autonomic symptoms and of light or noise sensitivity. Results Headache intensity was associated with lesions of the posterior insula, the operculum and the cerebellum. "Pulsating" headache occurred with widespread cortical and subcortical strokes. The presence of "tension-like" and "stabbing" headache was not related to specific lesion patterns. Nausea was associated with lesions in the posterior circulation territory. Cranial-autonomic symptoms were related to lesions of the parietal lobe, the somatosensory cortex (SI) and the middle temporal cortex. The presence of noise sensitivity was associated with cerebellar lesions, whereas light sensitivity was not related to specific lesions in our sample. Conclusion Headache phenotype in ischemic stroke appears to be related to specific ischemic lesion patterns.

Effect of Door-Locking Policy on Inpatient Treatment of Substance Use and Dual Disorders.

OBJECTIVE: Substance use treatment is often performed inside locked wards. We investigate the effects of adopting a policy of open-door treatment for a substance use treatment and dual diagnosis ward. METHODS: This is a prospective open-label study investigating 3-month study periods before opening (P1), immediately after (P2), and 1 year after the first period (P3). Data on committed patients, coercion (seclusion, forced medication, absconding events with subsequent police search), violence, and substance use was collected daily. We applied generalised estimating equation models. RESULTS: The mean daily number of patients with ongoing commitment changed from 2.64 (P1) to 2.12 (P2) to 0.96 (P3), corresponding to a reduction of relative risk (RR) for having an ongoing commitment by 20% in P2 (RR 0.80; 95% CI 0.66-0.98) and 67% in P3 (RR 0.33; 95% CI 0.25-0.42). The mean daily number of coercive events was 0.29, 0.13, and 0.05, corresponding to a risk for undergoing coercive measures reduced by 56% (RR 0.44; 95% CI 0.22-0.90) and 85% (RR 0.15; 95% CI 0.05-0.45). Substance use, violence or ward atmosphere did not differ significantly. CONCLUSIONS: Our results support findings from general psychiatric wards of reduced coercion after adopting a primarily open-door policy. However, coercive events were rare during all periods. The widespread practice of restricting the freedom of inpatients with substance use disorders by locking ward doors is highly questionable.

Headache in acute ischaemic stroke: a lesion mapping study.

Headache is a common symptom in acute ischaemic stroke, but the underlying mechanisms are incompletely understood. The aim of this lesion mapping study was to identify brain regions, which are related to the development of headache in acute ischaemic stroke. Patients with acute ischaemic stroke (n = 100) were assessed by brain MRI at 3 T including diffusion weighted imaging. We included 50 patients with stroke and headache as well as 50 patients with stroke but no headache symptoms. Infarcts were manually outlined and images were transformed into standard stereotaxic space using non-linear warping. Voxel-wise overlap and subtraction analyses of lesions as well as non-parametric statistics were conducted. The same analyses were carried out by flipping of left-sided lesions, so that all strokes were transformed to the same hemisphere. Between the headache group as well as the non-headache there was no difference in infarct volumes, in the distribution of affected vascular beds or in the clinical severity of strokes. The headache phenotype was tension-type like in most cases. Subtraction analysis revealed that in headache sufferers infarctions were more often distributed in two well-known areas of the central pain matrix: the insula and the somatosensory cortex. This result was confirmed in the flipped analysis and by non-parametric statistical testing (whole brain corrected P-value < 0.01). To the best of our knowledge, this is the first lesion mapping study investigating potential lesional patterns associated with headache in acute ischaemic stroke. Insular strokes turned out to be strongly associated with headache. As the insular cortex is a well-established region in pain processing, our results suggest that, at least in a subgroup of patients, acute stroke-related headache might be centrally driven.

Systemic thrombolysis in anterior spinal artery syndrome: what has to be considered?

Anterior spinal artery syndrome (ASAS) often leads to complete motor paralysis with poor clinical outcome. There is a lack of controlled clinical trials on acute treatment strategies in ASAS. However, systemic thrombolysis with recombinant tissue-plasminogen activator (rt-PA) might be a useful therapeutic option in ASAS. We report the management of a patient with ASAS below thoracic level 10, who was treated with intravenous thrombolysis. An 81 year old patient presented with flaccid paraplegia. After exclusion of aortal dissection, spinal tumour or haemorrhage, the patient was treated with intravenous rt-PA 3 h 40 min after symptom onset. The follow up magnetic resonance imaging (MRI) showed spinal infarction below thoracic segment 10. In the clinical course, the patient partially recovered lower limb muscle strength and was able to walk with assistance. To the best of our knowledge, this is the first case in the literature of ASAS with MRI-proven spinal ischemia and the application of rt-PA. Systemic thrombolysis seems to be justifiable in patients with ASAS after the rule-out of aortal dissection and spinal bleeding.

Morphological Abnormalities of Thalamic Subnuclei in Migraine: A Multicenter MRI Study at 3 Tesla.

The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p < 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233) = 6.79), anterior nucleus (F(1,237) = 7.38), and lateral dorsal nucleus (F(1,238) = 6.79). Moreover, reduced striatal volume (F(1,238) = 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine. SIGNIFICANCE STATEMENT: This multicenter imaging study shows morphological thalamic abnormalities in a large cohort of patients with episodic migraine compared with healthy subjects using state-of-the-art MRI and advanced, fully automated multiatlas segmentation techniques. The results stress that migraine is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling.

Dynamic Allostery of the Catabolite Activator Protein Revealed by Interatomic Forces.

The Catabolite Activator Protein (CAP) is a showcase example for entropic allostery. For full activation and DNA binding, the homodimeric protein requires the binding of two cyclic AMP (cAMP) molecules in an anti-cooperative manner, the source of which appears to be largely of entropic nature according to previous experimental studies. We here study at atomic detail the allosteric regulation of CAP with Molecular dynamics (MD) simulations. We recover the experimentally observed entropic penalty for the second cAMP binding event with our recently developed force covariance entropy estimator and reveal allosteric communication pathways with Force Distribution Analyses (FDA). Our observations show that CAP binding results in characteristic changes in the interaction pathways connecting the two cAMP allosteric binding sites with each other, as well as with the DNA binding domains. We identified crucial relays in the mostly symmetric allosteric activation network, and suggest point mutants to test this mechanism. Our study suggests inter-residue forces, as opposed to coordinates, as a highly sensitive measure for structural adaptations that, even though minute, can very effectively propagate allosteric signals.

Rapidly progressive intracranial artery stenosis in primary antiphospholipid syndrome.

Antiphospholipid antibody syndrome (APS) is usually a disease of young adults. In elderly stroke patients APS was not associated with progressive intracerebral stenosis in the past. Here, we report a 65-year-old patient who presented with recurrent ischemic strokes associated with progressive stenosis of the right middle cerebral artery. Antiphospholipid antibodies were detected and treatment with plasma exchange, tapered steroids, and anticoagulants was successful. This case demonstrates that APS should be considered also in elderly stroke patients. This is of particular relevance since APS confers a significant risk to angioplasty and stenting procedures which therefore should be avoided in APS.

Reduced volume of the nucleus accumbens in heroin addiction.

The neural mechanisms of heroin addiction are still incompletely understood, even though modern neuroimaging techniques offer insights into disease-related changes in vivo. While changes on cortical structure have been reported in heroin addiction, evidence from subcortical areas remains underrepresented. Functional imaging studies revealed that the brain reward system and particularly the nucleus accumbens (NAcc) play a pivotal role in the pathophysiology of drug addiction. The aim of this study was to investigate whether there was a volume difference of the NAcc in heroin addiction in comparison to healthy controls. A further aim was to correlate subcortical volumes with clinical measurements on negative affects in addiction. Thirty heroin-dependent patients under maintenance treatment with diacetylmorphine and twenty healthy controls underwent structural MRI scanning at 3T. Subcortical segmentation analysis was performed using FMRIB's Integrated Registration and Segmentation Tool function of FSL. The State-Trait Anxiety Inventory and the Beck Depression Inventory were used to assess trait anxiety and depressive symptoms, respectively. A decreased volume of the left NAcc was observed in heroin-dependent patients compared to healthy controls. Depression score was negatively correlated with left NAcc volume in patients, whereas a positive correlation was found between the daily opioid dose and the volume of the right amygdala. This study indicates that there might be structural differences of the NAcc in heroin-dependent patients in comparison with healthy controls. Furthermore, correlations of subcortical structures with negative emotions and opioid doses might be of future relevance for the investigation of heroin addiction.

Mobilization of CD133+ progenitor cells in patients with acute cerebral infarction.

Progenitor cells (PCs) contribute to the endogenous repair mechanism after ischemic events. Interleukin-8 (IL-8) as part of the acute inflammatory reaction may enhance PC mobilization. Also, statins are supposed to alter number and function of circulating PCs. We aimed to investigate PC mobilization after acute ischemic stroke as well as its association with inflammatory markers and statin therapy. Sixty-five patients with ischemic stroke were enrolled in the study. The number of CD133+ PCs was analyzed by flow cytometry. Blood samples were drawn within 24 hours after symptom onset and after 5 days. The number of CD133+ PCs increased significantly within 5 days (p<0.001). We found no correlation between CD133+ PCs and the serum levels of IL-8, IL-6, or C-reactive protein (CRP). Multivariate analysis revealed that preexisting statin therapy correlated independently with the increase of CD133+ PCs (p=0.001). This study showed a mobilization of CD133+ PCs in patients with acute cerebral infarction within 5 days after symptom onset. The early systemic inflammatory response did not seem to be a decisive factor in the mobilization of PCs. Preexisting statin therapy was associated with the increase in CD133+ PCs, suggesting a potentially beneficial effect of statin therapy in patients with stroke.

An allosteric signaling pathway of human 3-phosphoglycerate kinase from force distribution analysis.

3-Phosphogycerate kinase (PGK) is a two domain enzyme, which transfers a phosphate group between its two substrates, 1,3-bisphosphoglycerate bound to the N-domain and ADP bound to the C-domain. Indispensable for the phosphoryl transfer reaction is a large conformational change from an inactive open to an active closed conformation via a hinge motion that should bring substrates into close proximity. The allosteric pathway resulting in the active closed conformation has only been partially uncovered. Using Molecular Dynamics simulations combined with Force Distribution Analysis (FDA), we describe an allosteric pathway, which connects the substrate binding sites to the interdomain hinge region. Glu192 of alpha-helix 7 and Gly394 of loop L14 act as hinge points, at which these two secondary structure elements straighten, thereby moving the substrate-binding domains towards each other. The long-range allosteric pathway regulating hPGK catalytic activity, which is partially validated and can be further tested by mutagenesis, highlights the virtue of monitoring internal forces to reveal signal propagation, even if only minor conformational distortions, such as helix bending, initiate the large functional rearrangement of the macromolecule.