Beta-amyloid peptides(1-42) and (1-40) in the cerebrospinal fluid during pregnancy: a prospective observational study.

To evaluate changes in concentrations of selected biomarkers, neurotrophic factors, and growth factors in the cerebrospinal fluid during pregnancy. A prospective observational study was conducted in 32 pregnant women undergoing gynecological and obstetrical surgery under spinal anesthesia in a university hospital. Beta-amyloid(1-42) and beta-amyloid(1-40) peptides, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and vascular endothelial growth factor were analyzed in cerebrospinal fluid using an enzyme-linked immunosorbent assay. Eight women in second trimester pregnancy who underwent spinal anesthesia for gynecological or obstetrical surgery were compared with 24 matched women in third trimester pregnancies. CSF concentrations of beta-amyloid(1-42) were significantly higher in third trimester pregnancies (p = 0.025). During third trimester, the beta-amyloid ratio correlated with the vascular endothelial growth factor (rs = 0.657; p = 0.008). Higher concentrations of beta-amyloid(1-42) in cerebrospinal fluid of third trimester pregnancies and correlations between the beta-amyloid ratio and the vascular endothelial growth factor support the hypothesis that beta-amyloid peptides are involved in complex adaptive brain alterations during pregnancy.

[Hypotension induced by spinal anesthesia during cesarean section : Current treatment concepts]. / Spinalanästhesieinduzierte Hypotension bei Sectio caesarea : Aktuelle Behandlungskonzepte.

Arterial hypotension during cesarean delivery under spinal anesthesia can cause maternal and fetal adverse effects. Therefore, current guidelines recommend the continuous and preferably prophylactic use of vasopressors, emphasizing the use of alpha-agonists, such as phenylephrine. Besides a left lateral uterine displacement either an intravenous colloid preloading or a crystalloid co-loading is recommended. The blood pressure goal is to maintain a systolic arterial blood pressure of at least 90% of the initial baseline value and to avoid a drop to less than 80% of this baseline. To achieve this goal a prophylactic continuous phenylephrine infusion with an adjustable flow rate is recommended. It is advised to start with an initial dose of 25-50 µg/min, initiated immediately following the intrathecal injection of the local anesthetic and titrated according to the vital parameters. Parturients with cardiac diseases should be preoperatively evaluated following individual hemodynamic goals.

Cooperation in mind: Motor imagery of joint and single actions is represented in different brain areas.

In this study brain activity during motor imagery (MI) of joint actions, compared to single actions and rest conditions, was investigated using functional magnetic resonance imaging (fMRI). To the best of our knowledge, this is the first neuroimaging study which directly investigated the neural correlates of joint action motor imagery. Twenty-one healthy participants imagined three different motor tasks (dancing, carrying a box, wiping). Each imagery task was performed at two kinds: alone (single action MI) or with a partner (joint action MI). We hypothesized that to imagine a cooperative task would lead to a stronger cortical activation in motor related areas due to a higher vividness and intensification of the imagery. This would be elicited by the integration of the action simulation of the virtual partner to one's own action. Comparing the joint action and the single action condition with the rest condition, we found significant activation in the precentral gyrus and precuneus respectively. Furthermore the joint action MI showed higher activation patterns in the premotor cortex (inferior and middle frontal gyrus) compared to the single action MI. The imagery of a more vivid and engaging task, like our joint action imagery, could improve rehabilitation processes since a more distributed brain activity is found. Furthermore, the joint action imagery compared to single action imagery might be an appropriate BCI task due to its clear spatial distinction of activation.

Continuous Erroneous Feedback Processing during Deviation from the Road within a 2D Steering Task.

Recent research of our group indicated that erroneous feedback processing can not only be detected via established correlates in the electroencephalogram (EEG) for discrete stimuli, but also arises as modulations of the brain signals when faced with a continuous and periodic error signal. However, limitations in our previous paradigm prevented a definitive statement on the error signal as the exclusive source of the modulations, as well as on the connection between the observed error-related negativity (ERN)-like and error positivity (Pe)-like continuous correlates. Within a new paradigm involving EEG recordings of 10 participants, we disentangled modulation sources, substantiating our hypothesis that the observed periodicity arises primarily due to feedback processing. Further, we provide evidence that the continuous ERN- and Pe-like potentials are locked to separate phases in the error signal, rather than time-locked to a shared event, indicating that both potentials arise independently of one another.

Fluvastatin/fenofibrate vs. simvastatin/ezetimibe in patients with metabolic syndrome: different effects on LDL-profiles.

BACKGROUND: Patients with metabolic syndrome (MS) and type 2 diabetes (T2DM) show increased risk for coronary artery disease. Lipoprotein metabolism is characterized by elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) and predominance of atherogenic small, dense low-density lipoprotein (sdLDL), while low-density lipoprotein (LDL) cholesterol is only slightly elevated. METHODS: Multicentre, randomized, open-label cross-over study investigating the effect of combination of fluvastatin/fenofibrate (80/200 mg) (F&F) on LDL-subfractions compared with combination of simvastatin/ezetimibe (20/10 mg) (S&E) in patients with MS/T2DM. RESULTS: Seventy-five patients were randomized, 69 completed the study and LDL-subfractions of 56 patients were analysed. Thirty-eight out of 56 patients (68%) showed a profile dominated by sdLDL. In these, TG and total cholesterol (TC) were elevated compared with non-sdLDL patients. In all patients, reduction of TC and LDL cholesterol (LDL-C) by S&E was stronger than by F&F. The increase of HDL-C was stronger with S&E in the non-sdLDL group, whereas in the sdLDL group, there was no difference between treatments. In non-sdLDL patients, there was no effect on TG or LDL-radius. However, in the sdLDL group, F&F was more effective in reducing TG and increased LDL radius, whereas S&E reduced LDL radius even further. CONCLUSIONS: S&E is more efficient in reducing TC and LDL-C. This is also true for HDL-C increase in non-sdLDL patients. However, in patients with sdLDL, F&F was more efficient in reducing TG and increasing LDL radius.

Anemia in domestic cats: effect on hemoglobin components and whole blood oxygenation.

Phenylhydrazine-induced anemia in the domestic cat results in an increase in minor, high oxygen affinity hemoglobin B components and an accompanying decrease in the major, low affinity B component. This change is accompanied by an unusually large increase in erythrocytic adenosine triphosphate and 2,3-diphosphoglycerate, a slight decrease in the oxygen affinity of whole blood, and a large decrease in the Hill constant.

National survey of obstetric anaesthesia clinical practices in the republic of Austria.

BACKGROUND: The aim of this study was to describe the current obstetric anaesthetic practices in Austria by performing a comprehensive questionnaire survey. METHODS: A questionnaire was sent via email to key anaesthesiologists from obstetric anaesthesia departments of 81 hospitals registered at the Austrian Ministry of Health. RESULTS: Of 81 departments contacted, 65 (80%), covering 84% of annual births in Austria, responded to the 82-question survey. Epidural analgesia was offered universally, at a rate under 30% in 56 (86%) of respondent hospitals. The caesarean section rate was under 30% in 44 (68%) respondent obstetric units. All respondents provided spinal anaesthesia as the primary anaesthetic technique for elective caesarean section. Three (5%) respondents administered long-acting intrathecal morphine and 18 (28%) respondents did not routinely administer any intrathecal opioid. Wound infiltration for acute postoperative pain control was practiced in two (3%) respondent units. A transversus abdominis plane block was offered as rescue analgesia in 14 (22%) departments. Spinal hypotension was treated using a prophylactic phenylephrine infusion in two (3%) respondent hospitals. Prophylactic antibiotics were administered prior to skin incision by 31 (48%) respondents. CONCLUSION: This survey reveals that obstetric anaesthetic practices in Austria differ in part from current European and American guidelines. Findings will direct the national workforce on obstetric anaesthesia that aims to introduce into Austria practice guidelines, based on international collaborations and guideline recommendations.

Short-lived brain state after cued motor imagery in naive subjects.

Multi-channel electroencephalography recordings have shown that a visual cue, indicating right hand, left hand or foot motor imagery, can induce a short-lived brain state in the order of about 500 ms. In the present study, 10 able-bodied subjects without any motor imagery experience (naive subjects) were asked to imagine the indicated limb movement for some seconds. Common spatial filtering and linear single-trial classification was applied to discriminate between two conditions (two brain states: right hand vs. left hand, left hand vs. foot and right hand vs. foot). The corresponding classification accuracies (mean +/- SD) were 80.0 +/- 10.6%, 83.3 +/- 10.2% and 83.6 +/- 8.8%, respectively. Inspection of central mu and beta rhythms revealed a short-lasting somatotopically specific event-related desynchronization (ERD) in the upper mu and/or beta bands starting approximately 300 ms after the cue onset and lasting for less than 1 s.

Nicotinic acetylcholine receptor-subunit mRNAs in the mouse superior cervical ganglion are regulated by development but not by deletion of distinct subunit genes.

Mice with deletions of nicotinic ACh receptor (nAChR) subunit genes are valuable models for studying nAChR functions. We could previously show in the mouse superior cervical ganglion (SCG) that the absence of distinct subunits affects the functional properties of receptors. Here, we have addressed the question of whether deletions of the subunits alpha5, alpha7, or beta2 are compensated at the mRNA level, monitored by reverse transcription and quantitative real-time polymerase chain reaction. Relative to our reference gene, alpha3, which is expressed in all SCG nAChRs, mRNA levels of beta4 showed little change from birth until adult ages in intact ganglia of wild-type mice. In contrast, alpha4 declined sharply after birth and was barely detectable in adult animals. alpha5, alpha7, and beta2 subunit message levels also declined, though more slowly and less completely than alpha4. The subunits alpha6 and beta3 were detected by conventional polymerase chain reaction at very low levels, if at all, whereas alpha2 was never seen in any of our samples. The developmental profile of nAChR mRNA levels in the three knockout strains did not differ markedly from that of wild-type mice. Likewise, message levels of nAChR subunits were similar in cultures prepared from either wild-type or knockout animals. Our observations indicate a developmental regulation of nAChR subunit mRNAs in the SCG of mice after birth that was not affected by the three knockouts under investigation.

Treatment of very preterm preeclampsia via heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) apheresis: The Freiburg preeclampsia H.E.L.P.-Apheresis study.

OBJECTIVE: Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1. STUDY DESIGN: Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (<28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored. MAIN OUTCOME MEASURES: In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected. CONCLUSIONS: H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.

AML1 deletion in adult mice causes splenomegaly and lymphomas.

AML1 (RUNX1) encodes a DNA-binding subunit of the CBF transcription factor family and is required for the establishment of definitive hematopoiesis. AML1 is one of the most frequently mutated genes associated with human acute leukemia, suggesting that genetic alterations of the gene contribute to leukemogenesis. Here, we report the analysis of mice carrying conditional AML1 knockout alleles that were inactivated using the Cre/loxP system. AML1 was deleted in adult mice by inducing Cre activity to replicate AML1 deletions found in human MDS, familial platelet disorder and rare de novo human AML. At a latency of 2 months after induction, the thymus was reduced in size and frequently populated by immature double negative thymocytes, indicating defective T-lymphocyte maturation, resulting in lymphatic diseases with 50% penetrance, including atypical hyperplasia and thymic lymphoma. Metastatic lymphomas to the liver and the meninges were observed. Mice also developed splenomegaly with an expansion of the myeloid compartment. Increased Howell-Jolly body counts indicated splenic hypofunction. Thrombocytopenia occurred due to immaturity of mini-megakaryocytes in the bone marrow. Together with mild lymphocytopenia in the peripheral blood and increased fractions of immature cells in the bone marrow, AML1 deficient mice display features of a myelodysplastic syndrome, suggesting a preleukemic state.

Self-initiation of EEG-based brain-computer communication using the heart rate response.

Self-initiation, that is the ability of a brain-computer interface (BCI) user to autonomously switch on and off the system, is a very important issue. In this work we analyze whether the respiratory heart rate response, induced by brisk inspiration, can be used as an additional communication channel. After only 20 min of feedback training, ten healthy subjects were able to self-initiate and operate a 4-class steady-state visual evoked potential-based (SSVEP) BCI by using one bipolar ECG and one bipolar EEG channel only. Threshold detection was used to measure a beat-to-beat heart rate increase. Despite this simple method, during a 30 min evaluation period on average only 2.9 non-intentional switches (heart rate changes) were detected.

15 years of BCI research at Graz University of Technology: current projects.

Over the last 15 years, the Graz Brain-Computer Interface (BCI) has been developed and all components such as feature extraction and classification, mode of operation, mental strategy, and type of feedback have been investigated. Recent projects deal with the development of asynchronous BCIs, the presentation of feedback and applications for communication and control.

Evaluation of induced and evoked changes in EEG during selective attention to verbal stimuli.

BACKGROUND: Two challenges need to be addressed before bringing non-motor mental tasks for brain-computer interface (BCI) control to persons in a minimally conscious state (MCS), who can be behaviorally unresponsive even when proven to be consciously aware: first, keeping the cognitive demands as low as possible so that they could be fulfilled by persons with MCS. Second, increasing the control of experimental protocol (i.e. type and timing of the task performance). NEW METHOD: The goal of this study is twofold: first goal is to develop an experimental paradigm that can facilitate the performance of brain-teasers (e.g. mental subtraction and word generation) on the one hand, and can increase the control of experimental protocol on the other hand. The second goal of this study is to exploit the similar findings for mentally attending to someone else's verbal performance of brain-teaser tasks and self-performing the same tasks to setup an online BCI, and to compare it in healthy participants to the current "state-of-the-art" motor imagery (MI, sports). RESULTS: The response accuracies for the best performing healthy participants indicate that selective attention to verbal performance of mental subtraction (SUB) is a viable alternative to the MI. Time-frequency analysis of the SUB task in one participant with MCS did not reveal any significant (p<0.05) EEG changes, whereas imagined performance of one sport of participants' choice (SPORT) revealed task-related EEG changes over neurophysiological plausible cortical areas. COMPARISON WITH EXISTING METHODS: We found that mentally attending to someone else's verbal performance of brain-teaser tasks leads to similar results as in self-performing the same tasks. CONCLUSIONS: In this work we demonstrated that a single auditory selective attention task (i.e. mentally attending to someone else's verbal performance of mental subtraction) can modulate both induced and evoked changes in EEG, and be used for yes/no communication in an auditory scanning paradigm.

From classic motor imagery to complex movement intention decoding: The noninvasive Graz-BCI approach.

In this chapter, we give an overview of the Graz-BCI research, from the classic motor imagery detection to complex movement intentions decoding. We start by describing the classic motor imagery approach, its application in tetraplegic end users, and the significant improvements achieved using coadaptive brain-computer interfaces (BCIs). These strategies have the drawback of not mirroring the way one plans a movement. To achieve a more natural control-and to reduce the training time-the movements decoded by the BCI need to be closely related to the user's intention. Within this natural control, we focus on the kinematic level, where movement direction and hand position or velocity can be decoded from noninvasive recordings. First, we review movement execution decoding studies, where we describe the decoding algorithms, their performance, and associated features. Second, we describe the major findings in movement imagination decoding, where we emphasize the importance of estimating the sources of the discriminative features. Third, we introduce movement target decoding, which could allow the determination of the target without knowing the exact movement-by-movement details. Aside from the kinematic level, we also address the goal level, which contains relevant information on the upcoming action. Focusing on hand-object interaction and action context dependency, we discuss the possible impact of some recent neurophysiological findings in the future of BCI control. Ideally, the goal and the kinematic decoding would allow an appropriate matching of the BCI to the end users' needs, overcoming the limitations of the classic motor imagery approach.

Hydrophobic lung surfactant proteins B and C remain associated with surface film during dynamic cyclic area changes.

The biophysical activity of lung surfactant depends, to a large extent, on the presence of the hydrophobic surfactant proteins B (SP-B) and C (SP-C). The role of these proteins in lipid adsorption and lipid squeeze-out under dynamic conditions simulating breathing is not yet clear. Therefore, the aim of this study was to investigate the interaction of spread hydrophobic surfactant proteins with phospholipids in a captive-bubble surfactometer during rapid cyclic area changes (6 cycles/min). We found that SP-B and SP-C facilitated the rapid transport of lipids into the air-water interface in a concentration-dependent manner (threshold concentration > or = 0.05:0.5 mol% SP-B/SP-C). Successive rapid cyclic area changes did not affect the concentration-dependent lipid adsorption process, suggesting that SP-B and SP-C remained associated with the surface film.

Production of surfactant protein C in the baculovirus expression system: the information required for correct folding and palmitoylation of SP-C is contained within the mature sequence.

Surfactant protein C (SP-C) is synthesized in the alveolar type II cells of the lung as a 21 kDa propeptide which is proteolytically processed to a 4.2 kDa mature active form. The main function of this extremely hydrophobic protein is to enhance lipid insertion into the air/liquid interface in the lung upon inhalation. This is necessary to maintain a relatively low surface tension at this interface during breathing. In this report we describe the production of mature human SP-C in the baculovirus expression system. The recombinant protein contains a secondary structure with a high alpha-helical content (73%), comparable to native SP-C, as determined by circular dichroism and attenuated total reflection Fourier transform infrared analysis. The expressed protein is a mixture of dipalmitoylated (15%) and non-palmitoylated SP-C. This suggests that the information required for palmitoylation is contained within the sequence of the mature protein. The activity of the protein to insert phospholipids into a preformed monolayer of lipids at an air/liquid interface was determined with a captive bubble surfactometer. Recombinant SP-C significantly reduced the surface tension at the air/liquid interface during dynamic expansion and compression. We conclude that correctly folded, dipalmitoylated and active SP-C can be expressed in the baculovirus expression system. Our results may facilitate investigations into the relation between structure and function of SP-C and into protein palmitoylation in general.

Classification of unconscious like/dislike decisions: First results towards a novel application for BCI technology.

More and more applications for BCI technology emerge that are not restricted to communication or control, like gaming, rehabilitation, Neuro-IS research, neuro-economics or security. In this context a so called passive BCI, a system that derives its outputs from arbitrary brain activity for enriching a human-machine interaction with implicit information on the actual user state will be used. Concretely EEG-based BCI technology enables the use of signals related to attention, intentions and mental state, without relying on indirect measures based on overt behavior or other physiological signals which is an important point e.g. in Neuromarketing research. The scope of this pilot EEG-study was to detect like/dislike decisions on car stimuli just by means of ERP analysis. Concretely to define user preferences concerning different car designs by implementing an offline BCI based on shrinkage LDA classification. Although classification failed in the majority of participants the elicited early (sub) conscious ERP components reflect user preferences for cars. In a broader sense this study should pave the way towards a "product design BCI" suitable for neuromarketing research.

Immuno-magnetoliposomes targeting activated platelets as a potentially human-compatible MRI contrast agent for targeting atherothrombosis.

To detect unstable atherosclerotic plaques early and noninvasively would be of great clinical interest. Activated platelets are an interesting molecular target for detecting early lesions or unstable plaques. We therefore developed an MRI contrast agent consisting of magnetoliposomes (ML) linked to an antibody (anti-LIBS) specifically targeting the ligand-induced binding site of the activated GPIIb/IIIa receptor of platelets. ML were prepared by dual centrifugation (DC). ML pegylation up to a total PEG content of 7.5 mol% positively influenced the stability and amount of entrapped SPIOs, and also reduced SPIO-membrane interactions, while higher PEG contents destabilized PEG-ML. Stable anti-LIBS-ML with high amounts of entrapped SPIOs (∼86%, ∼0.22 mol Fe/mol liposomal lipid) and high MRI sensitivity (relaxivity r2 = 422 s(-1) mM(-1) and r2(∗) = 452 s(-1) mM(-1)) were obtained by coupling anti-LIBS to ML in a two-step post-insertion technique. We confirmed specific binding to the GPIIb/IIIa receptor's activated conformation on activated human platelets and cell lines expressing activated GPIIb/IIIa receptor ex vivo. The immuno-ML obtained in this study constitute an important step towards developing a potentially human-compatible MRI contrast agent for the timely detection of plaque rupture by targeting activated platelets.

Surfactant replacement therapy in acute respiratory distress syndrome from viral pneumonia.

A modified natural surfactant was administered to a patient with life-threatening adult respiratory distress syndrome caused by viral pneumonia. Subsequently, there was a marked improvement in gas exchange. In order to assess the mechanism for improved oxygenation, computed tomography of the lungs was done. Quantitative analysis of the scans taken before and after surfactant administration indicates that improvement in gas exchange was largely due to the expansion of underinflated and collapsed lung areas. Although this is a single case report, it provides insight into the possible beneficial effect of instilled surfactant in severe respiratory distress from viral pneumonia.