[Telemedicine in stroke-pertinent to stroke care in Germany]. / Telemedizin in der Schlaganfallversorgung ­ versorgungsrelevant für Deutschland.

BACKGROUND AND OBJECTIVE: Telemedical stroke networks improve stroke care and provide access to time-dependent acute stroke treatment in predominantly rural regions. The aim is a presentation of data on its utility and regional distribution. METHODS: The working group on telemedical stroke care of the German Stroke Society performed a survey study among all telestroke networks. RESULTS: Currently, 22 telemedical stroke networks including 43 centers (per network: median 1.5, interquartile range, IQR, 1-3) as well as 225 cooperating hospitals (per network: median 9, IQR 4-17) operate in Germany and contribute to acute stroke care delivery to 48 million people. In 2018, 38,211 teleconsultations (per network: median 1340, IQR 319-2758) were performed. The thrombolysis rate was 14.1% (95% confidence interval 13.6-14.7%) and transfer for thrombectomy was initiated in 7.9% (95% confidence interval 7.5-8.4%) of ischemic stroke patients. Financial reimbursement differs regionally with compensation for telemedical stroke care in only three federal states. CONCLUSION: Telemedical stroke care is utilized in about 1 out of 10 stroke patients in Germany. Telemedical stroke networks achieve similar rates of thrombolysis and transfer for thrombectomy compared with neurological stroke units and contribute to stroke care in rural regions. Standardization of network structures, financial assurance and uniform quality measurements may further strengthen the importance of telestroke networks in the future.

[Left atrial appendage closure in non-valvular atrial fibrillation]. / Verschluss des linken Vorhofohrs bei nichtvalvulärem Vorhofflimmern.

Atrial fibrillation is the most frequent cardiac arrhythmia worldwide, causing approximately 20% of all ischemic strokes. Therefore, oral anticoagulation is recommended in patients with atrial fibrillation with at least a moderate risk of stroke; however, there is a significant proportion of patients who cannot undergo long-term oral anticoagulation. As the left atrial appendage is of major relevance for atrial fibrillation-induced thrombus formation, catheter-based or surgical closure of the left atrial appendage appears to be a promising therapeutic option. Large registry studies including patients with catheter-based left atrial appendage closure have proven its effectiveness and a decreasing procedure-related complication rate. This review article summarizes the current knowledge and introduces major ongoing randomized studies, which will investigate the impact of left atrial appendage closure on stroke prevention. The authors hope that the results of the randomized CLOSURE AF trial, which is funded by the German Center for Cardiovascular Research e. V. and is now recruiting patients in Germany, will help to solve many of the currently prevalent clinical questions.

[ESC guidelines on atrial fibrillation 2016 : Summary of the most relevant recommendations and modifications]. / ESC-Leitlinien zum Vorhofflimmern 2016 : Zusammenfassung der wichtigsten Empfehlungen und Neuerungen.

The first European Society of Cardiology (ESC) guidelines on atrial fibrillation (AF) developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) were published in August 2016. These guidelines replace the revised guidelines from 2012 and contain some interesting new aspects. The topics range from the pathophysiology through diagnostics, therapy and stroke prevention up to special clinical situations, such as atrial fibrillation in cardiopathy, sport and pregnancy. Early screening, patient informed consent, individualized therapy and the modification of factors promoting atrial fibrillation are of particular importance. The guidelines recommend the establishment of AF heart teams, containing specialists from various disciplines. The guidelines also underline the importance of non-vitamin K­dependent oral anticoagulants (NOAC) for stroke prevention compared to standard anticoagulants with vitamin K antagonists. For symptomatic and especially paroxysmal atrial fibrillation, the guidelines emphasize the importance of an antiarrhythmic treatment with catheter ablation and/or pharmaceutical antiarrhythmic therapy in addition to a frequency regulating therapy.

Hot topic: investigating the risk of violative meat residues in bob veal calves fed colostrum from cows treated at dry-off with cephapirin benzathine.

The objective was to conduct a study to investigate if violative meat residues are detected in very young bob veal calves that are fed first-milking colostrum harvested from cows that were dry treated, on-label, with cephapirin benzathine. First-milking colostrum was collected from cows that were given intramammary treatment at dry off, on-label, with cephapirin benzathine (ToMORROW, Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Newborn bull calves meeting study inclusion criteria were removed from their dams shortly after birth and before suckling, and assigned to 1 of 2 trials. For the first trial, 6 treated calves were fed 3.8L of fresh maternal colostrum and 1 control calf was fed 1.5 doses of a plasma-derived colostrum replacer (Secure Calf Colostrum Replacer, VitaPlus Inc., Madison, WI) within 1h after birth. For the second trial, 5 treated calves were fed 3.8L of fresh maternal colostrum and 1 control calf was fed 1.5 doses of Secure Calf Colostrum Replacer within 1h after birth. All calves were humanely euthanized at 24h (trial 1) or 48h (trial 2) of age, and tissues were harvested for antimicrobial residue testing. Samples of maternal colostrum and colostrum replacer were also submitted for antimicrobial residue testing. Kidneys collected from all study calves tested negative for cephapirin benzathine residues when using both the KIS assay (Charm Sciences, Lawrence, MA) and liquid chromatography-tandem mass spectrometry analysis. The potential transfer of cephapirin from cows treated on-label at dry off to calves via colostrum may not be a significant source of cephapirin residues in veal tissues.

Treadmill vs. overground trotting - a comparison of two kinetic measurement systems.

Force plates are considered the gold standard for kinetic gait analysis, benefiting from measuring three-dimensional ground reaction forces. Nevertheless, the major disadvantage is that many trials are required during overground locomotion to capture adequate single-limb contacts. Additionally, the dogs slightly change velocities during overground walking, influencing kinetic and kinematic gait parameters. An alternative is using an instrumented treadmill that benefits from capturing many steady-state gait cycles at a constant speed quickly. The goal of this study was (1) to compare overground with treadmill locomotion and (2) to compare the instrumented treadmill with force plates for dogs kinetics measurements. Twelve client-owned dogs were measured during treadmill trotting while the treadmill was placed on force plates. Additionally, the dogs were measured during trotting along an alley over eight force plates. Bland-Altman plots, Pearson's (r), and concordance correlation coefficients (rc) were computed to explore the relative and general agreement between the measurement methods and overground and treadmill trotting. Overground and treadmill trotting gave an excellent agreement in peak vertical forces and impulses (r > 0.9, rc > 0.9). The instrumented treadmill showed similar force-time curves in shape and size and provided an excellent congruity for all parameters compared to force plates (r > 0.8, rc > 0.8). As a reliable tool in measuring key gait parameters, the instrumented treadmill may benefit from fast and reproducible data comparable to overground trotting.

[Neurological aspects of chronic heart failure]. / Neurologische Aspekte bei chronischer Herzinsuffizienz.

Chronic heart failure (CHF) is one of the leading causes of hospitalization, morbidity and mortality. Moreover, there is a high rate of neurological as well as neuropsychological comorbidities, namely ischemic stroke, structural brain alterations, cognitive impairment, sleep apnea and possible side-effects of HF medication such as delirium or (intracerebral) hemorrhage. The higher stroke risk in patients with HF increases further with age, concomitant arterial hypertension or atrial fibrillation (AF). In women the stroke risk increases with reduced ejection fraction (EF). In general stroke in HF patients is associated with a poor outcome and higher mortality, which is increased more than 2-fold. Furthermore, approximately 25-80% of all patients with CHF experience cognitive impairments such as decreased attention and concentration, memory loss, diminished psychomotor reaction time and decreased executive functions. Cognitive impairment in patients with HF has been linked to losses in gray matter, (silent) ischemic strokes, decreased cerebral perfusion and higher mortality. Moreover, sleep apnea occurs in more than half of all patients with CHF and reduced EF. However, prospective studies are needed to test whether early detection and optimal treatment of HF reduces the burden of neurological and neuropsychological sequelae.

[Left atrial appendage occlusion in patients with nonvalvular atrial fibrillation : Present evidence, ongoing studies, open questions]. / Verschluss des linken Vorhofohrs bei nichtvalvulärem Vorhofflimmern : Datenlage, aktuelle Studien, offene Fragen.

About every fifth ischemic stroke is caused by atrial fibrillation. Oral anticoagulation is highly effective in secondary stroke prevention, but a relevant portion of patients with atrial fibrillation is not (permanently) anticoagulated for a variety of reasons. Based on present evidence, no general recommendation can be given for left atrial appendage occlusion in patients with nonvalvular atrial fibrillation. However, left atrial appendage occlusion is a treatment option after severe anticoagulation-related bleeding, if the cause of bleeding is not treatable. Left atrial appendage occlusion is critical in patients with a relative contraindication for oral anticoagulation or lack of adherence to given medication. It seems to be important that further randomized studies confirm a benefit of left atrial appendage occlusion in selected patients with nonvalvular atrial fibrillation. In addition, it is vital to clarify whether discontinuation of antiplatelets is feasible after catheter-based left atrial appendage occlusion, as antiplatelets are associated with a risk of bleeding. Within this review article, we discuss present evidence, gaps of knowledge and provide an overview on ongoing clinical studies. In addition, we summarize the design of the CLOSURE-AF study. This randomized multicenter study will start recruitment soon and is funded by the German Center for Cardiovascular Research e. V.

Viscosity measurements on very small capillary blood samples.

Viscosity measurements on very small capillary blood samples could be of considerable clinical interest. We have developed an oscillating viscometer for very small volumes, which consists of a glass capillary containing 7 mul of blood, which is part of an oscillating torsional resonator. The damping of the sinusoidal oscillations depends on the density and viscosity of the fluid, which allows blood viscosity measurements. The instrument was first evaluated in comparison with a standard blood viscometer (Contraves LS 30). Blood from healthy volunteers anticoagulated with EDTA was adjusted to hematocrit levels of 20, 30, 40, 50, and 60%, respectively. A strong correlation was found between hematocrit and oscillating viscosity (y=0.17x-2.05, r=0.969, p<0.0001) and between oscillating and conventional high shear viscosity (y=1.11x-0.62, r=0.971, p<0.0001). Blood viscosity measured in venous or capillary blood of normal subjects was similar (p=0.63). Bedside viscosity measurements on capillary blood drawn from a finger prick during routine blood glucose measurements in patients with diabetes mellitus showed lower blood viscosity than controls (3.62+/-0.87 vs 4.79+/-0.59 mPa.s, p=0.0007), which is in contrast to earlier publications, and may be explained by the lower hematocrit in our diabetic patients (34.7+/-6.0% vs. 43.1+/-1.9%, p<0.0001). Blood viscosity was independent of the actual glucose level (range 3-17 mmol/l). Capillary blood anticoagulated with EDTA was drawn by heel prick from 23 newborns. Blood viscosity was higher (5.66 +/-2.47 mPa.s) than in adult controls (see above), which could be explained by the dependence on the higher hematocrit (46.4 +/-8.6%). We conclude that viscosity measurements can be made on very small samples such as capillary blood from diabetic patients or newborn babies with this new oscillating viscometer. It remains to be determined if such new informations have clinical implications.

Climate induced human demographic and cultural change in northern Europe during the mid-Holocene.

The transition from hunter-gatherer-fisher groups to agrarian societies is arguably the most significant change in human prehistory. In the European plain there is evidence for fully developed agrarian societies by 7,500 cal. yr BP, yet a well-established agrarian society does not appear in the north until 6,000 cal. yr BP for unknown reasons. Here we show a sudden increase in summer temperature at 6,000 cal. yr BP in northern Europe using a well-dated, high resolution record of sea surface temperature (SST) from the Baltic Sea. This temperature rise resulted in hypoxic conditions across the entire Baltic sea as revealed by multiple sedimentary records and supported by marine ecosystem modeling. Comparison with summed probability distributions of radiocarbon dates from archaeological sites indicate that this temperature rise coincided with both the introduction of farming, and a dramatic population increase. The evidence supports the hypothesis that the boundary of farming rapidly extended north at 6,000 cal. yr BP because terrestrial conditions in a previously marginal region improved.

Oscillating viscometer--evaluation of a new bedside test.

A viscometer for bedside blood measurements was developed, consisting of an oscillating resonator probe mounted directly into a disposable vacutainer tube for blood withdrawal. It was tested in vitro on blood samples with variable hematocrits (20-60%), increasing fibrinogen concentrations (0-20 g/l), increasing concentrations of an admixed radiographic contrast medium and erythrocyte suspensions in dextran 40 and dextran 70. Results were compared with those obtained with a conventional Couette viscometer. Oscillating viscometry yielded generally higher values than Couette viscometry, and had a good sensitivity for changes in hematocrit with a good correlation between the two methods (r=0.96, p<0.0001). Oscillating viscosity depended on the resonator frequency, it was higher at 3900 Hz than at 215 Hz, suggesting a viscoelastic behavior of blood. Erythrocyte aggregation, induced by increasing fibrinogen concentrations or dextran 70, affected oscillating viscometry. At a high frequency, i.e. a smaller penetration depth of the shear wave, oscillating viscosity tended to decrease, which suggests a depletion of the boundary layer from erythrocytes when they aggregate. At low frequency with a deeper shear wave penetration (about 50 microm), erythrocyte aggregation increased oscillating viscosity. Bedside tests in 17 patients with coronary heart disease and 10 controls confirmed the easy practicability of the test and showed lower oscillating viscosity in these patients despite higher fibrinogen concentrations presumably due to increased erythrocyte aggregation. We conclude that oscillating viscometry is an interesting bedside test, which is capable of providing new information on the biorheology of the erythrocyte-poor boundary layer near the vessel wall.

Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions.

Transforming growth factor beta (TGF-beta) is abundant in bone and has complex effects on osteolysis, with both positive and negative effects on osteoclast differentiation, suggesting that it acts via more than one mechanism. Osteoclastogenesis is determined primarily by osteoblast (OB) expression of the tumor necrosis factor (TNF)-related molecule receptor activator of NF-kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), which are increased and decreased, respectively, by osteolytic factors. A RANKL-independent osteoclastogenic mechanism mediated by TNF-alpha has also been shown. Therefore, we investigated TGF-beta effects on osteoclast formation in culture systems in which osteoclastogenic stimulus is dependent on OBs and culture systems where it was provided by exogenously added RANKL or TNF-alpha. Both OPG and TGF-beta inhibited osteoclast formation in hemopoietic cell/OB cocultures, but the kinetics of their action differed. TGF-beta also inhibited osteoclastogenesis in cocultures of cells derived from OPG null (opg-/-) mice. TGF-beta strongly decreased RANKL messenger RNA (mRNA) expression in cultured osteoblasts, and addition of exogenous RANKL to TGFbeta-inhibited cocultures of opg-/- cells partially restored osteoclastogenesis. Combined, these data indicate that the inhibitory actions of TGF-beta were mediated mainly by decreased OB production of RANKL. In contrast, in the absence of OBs, TGF-beta greatly increased osteoclast formation in recombinant RANKL- or TNF-alpha-stimulated cultures of hemopoietic cells or RAW 264.7 macrophage-like cells to levels several-fold greater than attainable by maximal stimulation by RANKL or TNF-alpha. These data suggest that TGF-beta may increase osteoclast formation via action on osteoclast precursors. Therefore, although RANKL (or TNF-alpha) is essential for osteoclast formation, factors such as TGF-beta may powerfully modify these osteoclastogenic stimuli. Such actions may be critical to the control of physiological and pathophysiological osteolysis.

beta-adrenergic receptor stimulation selectively inhibits IL-12p40 release in microglia.

The cytokine interleukin-12 (IL-12) is mainly produced in response to bacterial or parasitic infections. We examined the capacity of mouse brain microglia to release IL-12 forms upon challenge with bacterial lipopolysaccharide (LPS) and studied its modulation by sympathomimetics. LPS evoked the release of IL-12p40 whereas the heterodimeric form, IL-12p70 was virtually undetectable. Sympathomimetics such as salbutamol dose-dependently inhibited IL-12p40 release, whereas the production of IL-6, TNFalpha and MIP-1alpha was only marginally influenced. The inhibitory effect of salbutamol could be abolished by beta-antagonists, such as oxprenolol. The cAMP-elevating agent forskolin could mimic the effects of beta-agonists, indicating that IL-12p40 release inhibition involves intracellular cAMP accumulation. While microglial IL-12p40 may play a role in the regulation of IL-12p70 bioactivity, microglial release is itself modulated by IL-12p70. Recombinant IL-12p70 was found to enhance the LPS-evoked release of MIP-1alpha and to have a biphasic effect on both TNFalpha and MIP-1alpha with release augmentation at lower and attenuation at higher doses. Finally, no functional correlation was found between the release of IL-12p40 and the induction of Kv1.3 potassium channels, another marker of microglial activation. Taken together, beta(2)-adrenoreceptor-mediated effects on microglial cyto- and chemokine release via cAMP accumulation could modulate inflammatory cascades during bacterial infections.

A newly designed oscillating viscometer for blood viscosity measurements.

A newly designed type of oscillating viscometer is described. The viscometer consists of either a tube or a rod oscillating at a resonance frequency with amplitudes in the micro- and nanometer range. A fluid flowing through the tube or surrounding the rod damps the torsional oscillations. The increase in the damping depends on the viscosity of the fluid and is used to determine viscosity. It was found that viscosity measurements are feasible during blood flow. This new type of viscometer may be useful to the study of biophysical properties of blood at the wall surface during flow and give new insights into blood flow. The device allows direct viscosity measurement on blood directly as it is drawn from the vein through the tube without any anticoagulant.

Rheological properties of blood as assessed with a newly designed oscillating viscometer.

A newly designed type of oscillating viscometer was tested for blood viscosity measurements. The viscometer consists of a probe (either a tube or a rod) oscillating at a resonance frequency with amplitudes in the micro- and nanometer range. The torsional oscillations are dampened by fluids flowing through the tube or surrounding the rod. The degree of damping depends on the viscosity of the fluid, which allows to measure viscosity. Data obtained with these instruments were compared with those obtained with a conventional Couette viscometer. An increase of erythrocyte aggregation by the addition of dextran 70 in vitro led to the expected increase of viscosity in the Couette viscometer; in the oscillating tube viscometer, however, it remained unchanged, which may be explained by a decreased erythrocyte concentration near the tube wall due to increased aggregation and flow of erythrocytes in the tube center. In ex vivo experiments on blood flowing without anticoagulant directly through the tube viscometer an inverse correlation between viscosity and fibrinogen concentration was found. This is in contrast to actual knowledge and may indicate that high fibrinogen levels have a beneficial rheological effect at the tube or vessel wall. Our data suggest that the new oscillating tube viscometer is an interesting tool, which may contribute to a more comprehensive understanding of blood flow.

[Material related aspects of surface structured endoprostheses]. / Werkstoffkundliche Aspekte oberflächenstrukturierter Endoprothesen.

In this article technical problems of surface-structured endoprostheses for cementless implantation are discussed. On the basis of four prostheses (two hip and two knee endoprostheses) various different porous coating technologies are compared. One sintered sphere layer, a cast sphere layer, a cast layer with "spongy-bone" structure and a plasma sprayed coating were compared. The quality of the bonding between the prosthesis and the porous surface layer was examined metallographically using polished specimens, with additional investigation of fraction surfaces of special tension test specimens. Additional information is given on the notch effect of the different coatings, in terms of a reduction in fatigue strength. The notch sensitivity differs for each material, and the reduction in fatigue strength is discussed for different implant alloys and different technologies for surface structuring. The investigation shows that the present quality of surface-structured endoprostheses is not satisfactory. We would like to thank the Dr. Johannes Heidenhain Foundation for financial support of this research.

High-power 808 nm ridge-waveguide diode lasers with very small divergence, wavelength-stabilized by an external volume Bragg grating.

We present data on ridge-waveguide diode lasers having a vertical far-field divergence of only 11.5 degrees (FWHM) owing to an appropriate waveguide design. The lasers emitted an optical power of more than 1 W into the spatial fundamental mode from a ridge width of 5 microm. The emission wavelength was stabilized to a narrow range around 808 nm by placing a volume Bragg grating in front of the outcoupling facet.

[Fluorine distribution in the enamel in the use of glass ionomer cements as bonding materials]. / Fluorverteilung im Schmelz bei Einsatz von Glasionomerzementen als Befestigungswerkstoff.

The rise in the fluorine content of dental enamel after bonding orthodontic attachments with glass ionomer cement (GIC) was analysed in an in vitro study. Twenty-four freshly extracted caries-free premolars from adolescent patients were available for investigation. The teeth were cleaved longitudinally in the oro-vestibular direction to obtain a test specimen and reference sample. The GIC Aquacem was used as bonding material. The fluorine was measured with an electron beam microprobe (Camebax SX 50) 10, 20, 40 and 80 days after bonding. A rise of fluorine in dental enamel of more than 120% was observed after the bonding procedure. This rise was especially rapid in the first ten days, and a saturation value was reached after 40 days. The depth of penetration into the dental enamel was 20 microns, and the surface spreading was at least 3 mm. An equilibrium state is attained between the 40th and 80th day. A preventive action on caries in the vicinity of attachments bonded with glass ionomer cement is to be expected owing to the accumulation of fluorine in the dental enamel.

[Increasing the adhesion of glass ionomer cements in bracket bonding]. / Uber die Erhöhung der Haftung von Glasionomerzementen beim Kleben von Brackets.

For attaching orthodontic brackets glass ionomer cements are being discussed as an alternative material to synthetic glues since they are less aggressive toward the tooth enamel. A serious disadvantage consists in a lower degree of adhesion to enamel. The adhesion can, however, be increased to some extent by enamel preparation. In order to investigate further improvement in this area, 250 freshly extracted bovine teeth were treated with 22 chemicals and their enamel-conditioning properties were tested. For the attachment of the brackets the glass ionomer cements AqaCem and Ketac-cem are used. Tensile shear tests were carried out with a Wolpert universal testing machine. Best results were obtained with the aromatic carbonacids benzoic acid and salicylic acid in acetonic solution. The mean adhesive power was 9.8 MPa. This means an increase of 38% as compared to other pre-conditioning materials such as polyacrylic acid. It can be assumed, that aromatic carbonacids as small, very reactive molecules can establish a closer contact to the phosphate groups of enamel than can the macromolecular polyacrylic acid. Thus, a further step on the way to using glass ionomer cements as a bracket bonding material seems to have been taken.