Early thrombosis prophylaxis with enoxaparin is not associated with hematoma expansion in patients with spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Early pharmacological deep vein thrombosis (DVT) prophylaxis is recommended by guidelines, but rarely started within 48 h. We aimed to analyze the effect of early (within 48 h) versus late (>48 h) DVT prophylaxis on hematoma expansion (HE) and outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed 134 consecutive patients admitted to a tertiary neurointensive care unit with diagnosed spontaneous ICH, without previous anticoagulation, severe coagulopathy, hematoma evacuation, early withdrawal of therapy or ineligibility for DVT prophylaxis according to our institutional protocol. Significant late HE was defined as ≥6 mL increase of hematoma volume between neuroimaging within 48 h and day 3-6. Multivariate analysis was performed to identify risk factors for late HE, poor 3-month outcome (modified Rankin Scale score ≥ 4) and mortality. RESULTS: Patients had a median Glasgow Coma Scale score of 14 [interquartile range (IQR), 10-15], ICH volume of 11 (IQR, 5-24) mL and were 71 (IQR, 61-76) years old. A total of 56% (n = 76) received early DVT prophylaxis, 37% (n = 50) received late DVT prophylaxis and 8 (6%) had unknown bleeding onset. Patients with early DVT prophylaxis had smaller ICH volume [9.5 (IQR, 4-18.5) vs. 17.5 (IQR, 8-29) mL, P = 0.038] and were more often comatose (26% vs. 10%, P = 0.025). Significant late HE [n = 5/134 (3.7%)] was associated with larger initial ICH volume (P = 0.02) and lower thrombocyte count (P = 0.03) but not with early DVT prophylaxis (P = 0.36). Early DVT prophylaxis was not associated with worse outcome. CONCLUSION: Significant late HE is uncommon and DVT prophylaxis within 48 h of symptom onset may be safe in selected patients with ICH.

Acyclovir resistance in herpes simplex virus type I encephalitis: a case report.

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Clusters of cortical spreading depolarizations in a patient with intracerebral hemorrhage: a multimodal neuromonitoring study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is associated with high morbidity and mortality. Cortical spreading depolarizations (CSDs) increase brain matrix metalloproteinase (MMP)-9 activity leading to perihematomal edema expansion in experimental ICH. METHODS: The purpose of this report is to describe cerebral metabolic changes and brain extracellular MMP-9 levels in a patient with CSDs and perihematomal edema expansion after ICH. RESULTS: We present a 66-year-old male patient with ICH who underwent craniotomy for hematoma evacuation. Multimodal neuromonitoring data of the perihematomal region revealed metabolic distress and increased MMP-9 levels in the brain extracellular fluid during perihematomal edema progression. At the same time, subdural electrocorticography showed clusters of CSDs, which disappeared after ketamine anesthesia on day six. Perihematomal edema regression was associated with decreasing cerebral MMP-9 levels. CONCLUSIONS: This novel association between clusters of CSDs, brain metabolic distress, and increased MMP-9 levels expands our knowledge about secondary brain injury after ICH. The role of ketamine after this devastating disorder needs further studies.

What is white?

To shed light on the perceptual basis of the color white, we measured settings of unique white in a dark surround. We find that settings reliably show more variability in an oblique (blue-yellow) direction in color space than along the cardinal axes of the cone-opponent mechanisms. This is against the idea that white perception arises at the null point of the cone-opponent mechanisms, but one alternative possibility is that it occurs through calibration to the visual environment. We found that the locus of maximum variability in settings lies close to the locus of natural daylights, suggesting that variability may result from uncertainty about the color of the illuminant. We tested this by manipulating uncertainty. First, we altered the extent to which the task was absolute (requiring knowledge of the illumination) or relative. We found no clear effect of this factor on the reduction in sensitivity in the blue-yellow direction. Second, we provided a white surround as a cue to the illumination or left the surround dark. Sensitivity was selectively worse in the blue-yellow direction when the surround was black than when it was white. Our results can be functionally related to the statistics of natural images, where a greater blue-yellow dispersion is characteristic of both reflectances (where anisotropy is weak) and illuminants (where it is very pronounced). Mechanistically, the results could suggest a neural signal responsive to deviations from the blue-yellow locus or an adaptively matched range of contrast response functions for signals that encode different directions in color space.

Switchable telescopic contact lens.

We present design and first demonstration of optics for a telescopic contact lens with independent optical paths for switching between normal and magnified vision. The magnified optical path incorporates a telescopic arrangement of positive and negative annular concentric reflectors to achieve 2.8 x magnification on the eye, while light passing through a central clear aperture provides unmagnified vision. We present an experimental demonstration of the contact lens mounted on a life-sized optomechanical model eye and, using a pair of modified commercial 3D television glasses, demonstrate electrically operated polarization switching between normal and magnified vision.

Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma: results of the 'Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study'.

BACKGROUND: ROTEM(®)/TEG(®) (rotational thromboelastometry) assays appear to be useful for the treatment of bleeding trauma patients. However, data on the prevalence and impact of abnormal ROTEM(®) assays are scarce. METHODS: This is a prospective cohort study of blunt trauma patients (Injury Severity Score ≥15 or Glasgow Coma Score ≤14) admitted to Innsbruck Medical University Hospital between July 2005 and July 2008. Standard coagulation tests, antithrombin (AT), prothrombin fragments (F1+2), thrombin-antithrombin complex (TAT), and ROTEM(®) assays were measured after admission. Data on 334 patients remained for final analysis. RESULTS: ROTEM(®) parameters correlated with standard coagulation tests (all Spearman r>0.5), and significant differences in mortality were detected for defined ROTEM(®) thresholds [FIBTEM 7 mm (21% vs 9%, P=0.006), EXTEM MCF (maximum clot firmness) 45 mm (25.4% vs 9.4%, P=0.001)]. EXTEM MCF was independently associated with early mortality [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.9-0.99] and MCF FIBTEM with need for red blood cell transfusion (OR 0.92, 95% CI 0.87-0.98). In polytrauma patients with or without head injury (n=274), the prevalence of low fibrinogen concentrations, impaired fibrin polymerization, and reduced clot firmness was 26%, 30%, and 22%, respectively, and thus higher than the prolonged international normalized ratio (14%). Hyperfibrinolysis increased fatality rates and occurred as frequently in isolated brain injury (n=60) as in polytrauma (n=274) (5%, 95% CI 1.04-13.92 vs 7.3%, 95% CI 4.52-11.05). All patients showed elevated F1+2 and TAT and low AT levels, indicating increased thrombin formation. CONCLUSIONS: Our data enlarge the body of evidence showing that ROTEM(®) assays are useful in trauma patients. Treatment concepts should focus on maintaining fibrin polymerization and treating hyperfibrinolysis.

Spatiotemporal averaging of perceived brightness along an apparent motion trajectory.

Objects are critical functional units for many aspects of visual perception and recognition. Many psychophysical experiments support the concept of an "object file" consisting of characteristics attributed to a single object on the basis of successive views of it, but there has been little evidence that object identity influences apparent brightness and color. In this study, we investigated whether the perceptual identification of successive flashed stimuli as views of a single moving object could affect brightness perception. Our target stimulus was composed of eight wedge-shaped sectors. The sectors were presented successively at different inter-flash intervals along an annular trajectory. At inter-flash intervals of around 100 ms, the impression was of a single moving object undergoing long-range apparent motion. By modulating the luminance between successive views, we measured the perception of luminance modulation along the trajectory of this long-range apparent motion. At the inter-flash intervals where the motion perception was strongest, the luminance difference was perceptually underestimated, and forced-choice luminance discrimination thresholds were elevated. Moreover, under such conditions, it became difficult for the observer to correctly associate or "bind" spatial positions and wedge luminances. These results indicate that the different luminances of wedges that were perceived as a single object were averaged along its apparent motion trajectory. The large spatial step size of our stimulus makes it unlikely that the results could be explained by averaging in a low-level mechanism that has a compact spatiotemporal receptive field (such as V1 and V2 neurons); higher level global motion or object mechanisms must be invoked to account for the averaging effect. The luminance averaging and the ambiguity of position-luminance "binding" suggest that the visual system may evade some of the costs of rapidly computing apparent brightness by adopting the assumption that the characteristics of an object are invariant over successive views.

Building a national hernia registry in South Africa: initial ventral hernia repair results from a diverse healthcare sector.

PURPOSE: The purpose of this paper was to introduce a new registry in a developing country by describing the demographics, management and 30-day outcomes of patients undergoing ventral hernia repair in the public and private healthcare sectors of South Africa. METHODS: This study was a retrospective review of a prospectively maintained hernia registry from the 1st of February 2019 to 29th of February 2020. RESULTS: 353 ventral hernia repair cases were recorded of which 47% were incisional hernias and the remainder were primary hernias. The median age was 54 years with even distribution of males and females. Half of the patients were obese with a median BMI of 31 kg/m2. The private sector performed 190 cases (54%) and the public sector 163 cases (46%). The public sector had more current smokers undergoing elective repairs, 28% vs 15%, p = 0.01 and performed more emergency repair cases, 21% vs 8%, p < 0.01. The majority (89%) of hernias were repaired with mesh and one-third were repaired laparoscopically. 30 day follow up was obtained in 30% of cases, the private sector had better follow up rates (42% vs 14%). CONCLUSION: Participation in the HIG (SA) registry was low with poor follow up over the first year. Ongoing prospective data capture on the HIG (SA) hernia registry will continue to provide further insights into hernia repair practices in South Africa.

Jupiter:observation of deuterated methane in the atmosphere.

A positive identification of singly deuterated methane has been made in the 4- to 5-micron spectrum of Jupiter.

Nosocomial ventriculitis and meningitis in neurocritical care patients.

BACKGROUND: External ventricular drainage (EVD) is frequently necessary in neurological and neurosurgical intensive care patients. A major complication of this procedure is an EVD-related venticulitis or meningitis. The purpose of this review is (1) to address the magnitude of the problem in the neurocritical care patient population, (2) to discuss the difficulties in providing an appropriate and timely diagnosis of this disease entity and (3) to propose an algorithm for both rapid diagnosis and appropriate therapy. METHODS: A MEDLINE literature search was carried out for studies from January 1990 through March 2008 reporting on ventriculostomy, EVD-related central nervous system infections, in particular ventriculitis and meningitis. RESULTS: EVD-related ventriculitis is a serious nosocomial complication in the neurocritical care setting where EVD catheters are frequently used for the management of elevated ICP secondary to acute hydrocephalus primarily caused by subarachnoid and intraventricular hemorrhage or traumatic brain injury. Infection rate is high with reported incidences in the range of 5 % up to more than 20 %. Predisposing factors for infection are non-adherence to rigid insertion and maintenance protocols, leakage of cerebrospinal fluid (CSF), catheter irrigation and the frequency of EVD manipulation. Diagnosis is frequently impaired either by the presence of systemic inflammation due to the primary disease or because the hemorrhagic CSF itself may cause an inflammatory reaction. Furthermore, the most common pathogens involved in EVD-related infections, i. e., staphylococci, initially provoke only a mild inflammatory response in the CSF and therefore patients rarely present with clear-cut clinical signs indicating severe central nervous system infection, in particular, ventriculitis. CONCLUSION: Nosocomial EVD-related ventriculitis is a significant cause of morbidity and mortality in critically ill neurological patients. Rapid diagnosis and prompt initiation of appropriate antimicrobial therapy is needed. A stepwise algorithm for the management of EVD-related ventriculitis is proposed.

rFVIIa--for acute rebleeding of a cerebral cavernous malformation.

Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa.

Behavioral characterization of the anterior injection model of subarachnoid hemorrhage.

BACKGROUND: The applicability of various neurological scores has not been sufficiently characterized in the anterior injection model of subarachnoid hemorrhage (SAH). Therefore this study was performed to evaluate different behavioral tests for quantifying disease severity. METHODS: Different volumes of autologous blood were injected stereotaxically into the prechiasmatic cistern of mice. Sham controls underwent the same procedure without blood injection. The following seven days after surgery, mice were evaluated for behavioral deficits by the SHIRPA score, beam balance and flex field analyses. Brains were further processed for histological analyses. RESULTS: Flex field analysis of SAH animals showed a significant reduction of locomotor activity compared to controls in the first two days after SAH. This reduction was more intense in animals with a higher amount of injected blood. The SHIRPA score revealed a significant reduction in motor behavior in SAH animals two days after surgery. A significant increase of GFAP expression, Fluoro Jade C and TUNEL positive cells as well as microthrombi was observed in SAH animals compared to sham controls in the early phase of SAH. There was a significant negative correlation between flex field righting and the number of degenerative neurons or microthrombi in the first two days after SAH. CONCLUSION: The results of flex field analysis and SHIRPA single test show behavioral and functional deficits in the first two days after SAH in parallel to histological alterations indicating neuronal damage. In summary these tests can be used as functional outcome parameters in the anterior injection model of SAH.

Simultaneous measurement of whole blood vitamin B1 and vitamin B6 using LC-ESI-MS/MS.

Vitamin B1 and B6 have recently been included in the Dutch clinical guidelines for the general practitioner in the differential diagnosis of dementia. To keep up with the sharp rise in the number of requests, an LC-MS/MS method using stable isotopes as internal standards was developed. The active vitamers thiamine pyrophosphate (TPP) and pyridoxal-5'-phosphate (PLP) in whole blood are simultaneously measured with a short run time of 2min. Whole blood is mixed with internal standard solution containing both TPP-d3 and PLP-d3, followed by deproteinization with a trichloroacetic acid (TCA) solution. A UPLC-MS/MS system from Waters™ was used for chromatographic separation and subsequent detection by electrospray ionization in the positive mode with mass transitions of 425.1>121.85 for TPP and 247.9>149.9 for PLP. The method is linear across the range of 12-4870 nmol/L for TPP and 6-4850 nmol/L for PLP. The mean intra-assay and inter-assay precision are 3.5% and 7.6% respectively for TPP and 3.4% and 6.1% for PLP. The relative matrix effect (TPP 97%, PLP 93%), recovery (TPP 99%, PLP 94%) and lower limit of quantification (TPP 12 nmol/L, PLP 6 nmol/L) meet the applied acceptance criteria. The comparison of the new LC-ESI-MS/MS method for TPP with our current HPLC-Fluorescence method for total thiamine yields the following equation: TPP LC-MS/MS=0.97×total thiamine HPLC - 10.61 (r2=0.94). The comparison of the new LC-ESI-MS/MS method for PLP with our current LC-ESI-MS/MS method results in PLP LC-MS/MS new=1.01×PLP LC-MS/MS old - 1.58 (r2=0.99). In conclusion, this LC-MS/MS based assay is characterized by simple sample processing with a short run time and comparison with the current methods is excellent. The new LC-MS/MS method is a convenient method to determine TPP and PLP in whole blood for both clinical routine and research applications.

The brain has a body: adaptive behavior emerges from interactions of nervous system, body and environment.

Studies of mechanisms of adaptive behavior generally focus on neurons and circuits. But adaptive behavior also depends on interactions among the nervous system, body and environment: sensory preprocessing and motor post-processing filter inputs to and outputs from the nervous system; co-evolution and co-development of nervous system and periphery create matching and complementarity between them; body structure creates constraints and opportunities for neural control; and continuous feedback between nervous system, body and environment are essential for normal behavior. This broader view of adaptive behavior has been a major underpinning of ecological psychology and has influenced behavior-based robotics. Computational neuroethology, which jointly models neural control and periphery of animals, is a promising methodology for understanding adaptive behavior.

Simulation of adaptive behavior.

Behaviors as diverse as swimming, withdrawal, escape, locomotion and feeding have been simulated using neuroethological and neurophysiological data obtained from a variety of animals. These simulations are providing new insights into the neural circuitry that generates adaptive behavior, as well as new ideas for the design of artificial autonomous devices.

Biorobotic approaches to the study of motor systems.

Biorobotics is a promising new area of research at the interface between biology and robotics. Robots can either be used as physical models of biological systems or be directly inspired by biological studies. A great deal of progress has recently been made in biorobotic studies of locomotion, orientation, and vertebrate arm control.

The prosthetic group of methylamine dehydrogenase from Pseudomonas AM1: evidence for a quinone structure.

The g-value and linewidth of ESR spectra of methylamine dehydrogenase (primary-amine:(acceptor) oxidoreductase (deaminating) EC 1.4.99.-) and methanol dehydrogenase (alcohol:(acceptor) oxidoreductase, EC 1.1.99.8) are very similar. This similarity is also reflected in electron-nuclear double resonance (ENDOR) results, the coupling constants of two protons in one enzyme equalling those in the other. The presence of a third proton in the ENDOR spectrum of methylamine dehydrogenase suggests a different structure or a different kind of interaction which can be related to the finding that the resolved ROSTHETIC GROUP IS PROTEIN-BOUND. The bound prosthetic group has a high redox-potential, supporting the conclusion from the ESR and ENDOR results that it is a quinone derivative.