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Biocomposite Materials Based on Carbonized Rice Husk in Biomedicine and Environmental Applications
(2020)
This chapter describes the prospects for biomedical and environmental engineering applications of heterogeneous materials based on nanostructured carbonized rice husk. Efforts in engineering enzymology are focused on the following directions: development and optimization of immobilization methods leading to novel biotechnological and biomedical applications; construction of biocomposite materials based on individual enzymes, multi-enzyme complexes and whole cells, targeted on realization of specific industrial processes. Molecular biological and biochemical studies on cell adhesion focus predominantly on identification, isolation and structural analysis of attachment-responsible biological molecules and their genetic determinants. The chapter provides a short overview of applications of the biocomposite materials based of nanostructured carbonized adsorbents. It emphasizes that further studies and better understanding of the interactions between CNS and microbial cells are necessary. The future use of living cells as biocatalysts, especially in the environmental field, needs more systematic investigations of the microbial adsorption phenomenon.
One of the priority trends of carbon nanotechnology is creation of nanocomposite systems. Such carbon nanostructured composites were produced using - raw materials based on the products of agricultural waste, such as grape stones, apricot stones, rice husk. These products have a - wide spectrum of application and can be obtained in large quantities. The Institute of Combustion Problems has carried out the work on synthesis of the nanostructured carbon sorbents for multiple applications including the field of biomedicine. The article presents the data on the synthesis and physico-chemical properties of carbonaceous sorbents using physicochemical methods of investigation: separation and purification of biomolecules; isolation of phytohormone - fusicoccin; adsorbent INGO-1 in the form of an adsorption column for blood detoxification, oral (entero) sorbent - INGO-2; the study of efferent and probiotic properties and sorption activity in regard to the lipopolysaccharide (LPS), new biocomposites - based on carbonized rice husk (CRH) and cellular microorganisms; the use of CRH in wound treatment. A new material for blood detoxication (INGO-1) has been obtained. Adsorption of p-cresyl sulfate and indoxyl sulfate has shown that active carbon adsorbent can remove clinically significant level of p-cresyl sulfate and indoxyl sulfate from human plasma. Enterosorbent INGO-2 possesses high adsorption activity in relation to Gram-negative bacteria and their endotoxins. INGO-2 slows down the growth of conditionally pathogenic microorganisms, without having a negative effect on bifido and lactobacteria. The use of enterosorbent INGO-2 for sorption therapy may provide a solution to a complex problem - detoxication of the digestive tract and normalization of the intestinal micro ecology. The immobilized probiotic called "Riso-lact" was registered at the Ministry of Health of the Republic of Kazakhstan as a biologically active food additive. The developed technology is patented and provides production of the medicine in the form of freeze-dried biomass immobilized in vials.
Conventional EEG devices cannot be used in everyday life and hence, past decade research has been focused on Ear-EEG for mobile, at-home monitoring for various applications ranging from emotion detection to sleep monitoring. As the area available for electrode contact in the ear is limited, the electrode size and location play a vital role for an Ear-EEG system. In this investigation, we present a quantitative study of ear-electrodes with two electrode sizes at different locations in a wet and dry configuration. Electrode impedance scales inversely with size and ranges from 450 kΩ to 1.29 MΩ for dry and from 22 kΩ to 42 kΩ for wet contact at 10 Hz. For any size, the location in the ear canal with the lowest impedance is ELE (Left Ear Superior), presumably due to increased contact pressure caused by the outer-ear anatomy. The results can be used to optimize signal pickup and SNR for specific applications. We demonstrate this by recording sleep spindles during sleep onset with high quality (5.27 μVrms).
Wearable EEG has gained popularity in recent years driven by promising uses outside of clinics and research. The ubiquitous application of continuous EEG requires unobtrusive form-factors that are easily acceptable by the end-users. In this progression, wearable EEG systems have been moving from full scalp to forehead and recently to the ear. The aim of this study is to demonstrate that emerging ear-EEG provides similar impedance and signal properties as established forehead EEG. EEG data using eyes-open and closed alpha paradigm were acquired from ten healthy subjects using generic earpieces fitted with three custom-made electrodes and a forehead electrode (at Fpx) after impedance analysis. Inter-subject variability in in-ear electrode impedance ranged from 20 kΩ to 25 kΩ at 10 Hz. Signal quality was comparable with an SNR of 6 for in-ear and 8 for forehead electrodes. Alpha attenuation was significant during the eyes-open condition in all in-ear electrodes, and it followed the structure of power spectral density plots of forehead electrodes, with the Pearson correlation coefficient of 0.92 between in-ear locations ELE (Left Ear Superior) and ERE (Right Ear Superior) and forehead locations, Fp1 and Fp2, respectively. The results indicate that in-ear EEG is an unobtrusive alternative in terms of impedance, signal properties and information content to established forehead EEG.
Introduction: In peripheral percutaneous (VA) extracorporeal membrane oxygenation (ECMO) procedures the femoral arteries perfusion route has inherent disadvantages regarding poor upper body perfusion due to watershed. With the advent of new long flexible cannulas an advancement of the tip up to the ascending aorta has become feasible. To investigate the impact of such long endoluminal cannulas on upper body perfusion, a Computational Fluid Dynamics (CFD) study was performed considering different support levels and three cannula positions.
Methods: An idealized literature-based- and a real patient proximal aortic geometry including an endoluminal cannula were constructed. The blood flow was considered continuous. Oxygen saturation was set to 80% for the blood coming from the heart and to 100% for the blood leaving the cannula. 50% and 90% venoarterial support levels from the total blood flow rate of 6 l/min were investigated for three different positions of the cannula in the aortic arch.
Results: For both geometries, the placement of the cannula in the ascending aorta led to a superior oxygenation of all aortic blood vessels except for the left coronary artery. Cannula placements at the aortic arch and descending aorta could support supra-aortic arteries, but not the coronary arteries. All positions were able to support all branches with saturated blood at 90% flow volume.
Conclusions: In accordance with clinical observations CFD analysis reveals, that retrograde advancement of a long endoluminal cannula can considerably improve the oxygenation of the upper body and lead to oxygen saturation distributions similar to those of a central cannulation.
In this paper, we will provide a feasible mission design for a multiple-rendezvous mission to Jupiter's Trojans. It is based on solar electric propulsion, as being currently used on the DAWN spacecraft, and other flight-proven technology. First, we have selected a set of mission objectives, the prime objective being the detection of water -especially subsurface water -to provide evidence for the Trojans' formation at large solar distances. Based on DAWN and other comparable missions, we have determined suitable payload instruments to achieve these objectives. Afterwards, we have designed a spacecraft that is able to carry the selected payload to the Trojan region and rendezvous successively with three target bodies within a maximum mission duration of 15 years. Accurate low-thrust trajectories have been obtained with a global low-thrust trajectory optimization program (InTrance). During the transfer from Earth to the first target, the spacecraft is propelled by two RIT-22 ion engines from EADS Astrium, whereas a single RIT-15 is used for transfers within the Trojan region to reduce the required power. For power generation, the spacecraft uses a multi-junction solar array that is supported by concentrators. To achieve moderate mission costs, we have restricted the launch mass to a maximum of 1600 kg, the maximum interplanetary injection capability of a Soyuz/Fregat launcher. Our final layout has a mass of 1400 kg, yielding a margin of about 14%. Nestor (a member of the L4-population) was determined as the first mission target. It can be reached within 4.6 years from launch. The fuel mass ratio for this transfer is about 35%. The stay time at Nestor is 1.2 years. Eurymedon was selected as the second target (transfer time 3.5 years, stay time 3.0 years) and Irus as the third target (transfer time 2.2 years). The transfers within the Trojan L4-population can be accomplished with fuel mass ratios of about 3% for each trajectory leg. Including the stay times in orbit around the targets, the mission can be accomplished within a total duration of about 14.5 years. According to our mission analysis, it is also feasible to fly to the L5-population with similar flight times. It has to be noted that -for a first analysis -we have taken only the named targets into account. Allowing also rendezvous with unnamed objects will very likely decrease the mission duration. Based on a scaling of DAWN's mission costs (due to comparable scientific instruments and mission objectives), and taking into account the longer mission duration and the potential re-use of already developed technology, we have estimated that these three rendezvous can be accomplished with a budget of about 250 Million Euros, i.e. about 25% of ROSETTA's budget.
A technology reference study for a solar polar mission is presented. The study uses novel analytical methods to quantify the mission design space including the required sail performance to achieve a given solar polar observation angle within a given timeframe and thus to derive mass allocations for the remaining spacecraft sub-systems, that is excluding the solar sail sub-system. A parametric, bottom-up, system mass budget analysis is then used to establish the required sail technology to deliver a range of science payloads, and to establish where such payloads can be delivered to within a given timeframe. It is found that a solar polar mission requires a solar sail of side-length 100–125 m to deliver a ‘sufficient value’ minimum science payload, and that a 2.5 μm sail film substrate is typically required, however the design is much less sensitive to the boom specific mass.
By DLR-contact, sample return missions to the large main-belt asteroid “19, Fortuna” have been studied. The mission scenario has been based on three ion thrusters of the RIT-22 model, which is presently under space qualification, and on solar arrays equipped with triple-junction GaAs solar cells. After having designed the spacecraft, the orbit-to-orbit trajectories for both, a one-way SEP mission with a chemical sample return and an all-SEP return mission, have been optimized using a combination of artificial neural networks with evolutionary algorithms. Additionally, body-to-body trajectories have been
investigated within a launch period between 2012 and 2015. For orbit-to-orbit calculation, the launch masses of the hybrid mission and of the all-SEP mission resulted in 2.05 tons and 1.56 tons, respectively, including a scientific payload of 246 kg. For the related transfer
durations 4.14 yrs and 4.62 yrs were obtained. Finally, a comparison between the mission scenarios based on SEP and on NEP have been carried out favouring clearly SEP.
There is common agreement within the scientific community that in order to understand our local galactic environment it will be necessary to send a spacecraft into the region beyond the solar wind termination shock. Considering distances of 200 AU for a new mission, one needs a spacecraft traveling at a speed of close to 10 AU/yr in order to keep the mission duration in the range of less than 25 yrs, a transfer time postulated by European Space Agency (ESA). Two propulsion options for the mission have been proposed and discussed so far: the solar sail propulsion and the ballistic/radioisotope-electric propulsion (REP). As a further alternative, we here investigate a combination of solar-electric propulsion (SEP) and REP. The SEP stage consists of six 22-cms diameter RIT-22 ion thrusters working with a high specific impulse of 7377 s corresponding to a positive grid voltage of 5 kV. Solar power of 53 kW at begin of mission (BOM) is provided by a lightweight solar array.
Under DLR-contract, Giessen University and DLR Cologne are studying solar-electric propulsion missions (SEP) to the outer regions of the solar system. The most challenging reference mission concerns the transport of a 1.35-tons chemical lander spacecraft into an 80-RJ circular orbit around Jupiter, which would enable to place a 375 kg lander with 50 kg of scientific instruments on the surface of the icy moon "Europa". Thorough analyses show that the best solution in terms of SEP launch mass times thrusting time would be a two-stage EP module and a triple-junction solar array with concentrators which would be deployed step by step. Mission performance optimizations suggest to propel the spacecraft in the first EP stage by 6 gridded ion thrusters, running at 4.0 kV of beam voltage, which would save launch mass, and in the second stage by 4 thrusters with 1.25 to 1.5 kV of positive high voltage saving thrusting time. In this way, the launch mass of the spacecraft would be kept within 5.3 tons. Without a launcher's C3 and interplanetary gravity assists, Jupiter might be reached within about 4 yrs. The spiraling-down into the parking orbit would need another 1.8 yrs. This "large mission" can be scaled down to a smaller one, e.g., by halving all masses, the solar array power, and the number of thrusters. Due to their reliability, long lifetime and easy control, RIT-22 engines have been chosen for mission analysis. Based on precise tests, the thruster performance has been modeled.
An Interstellar – Heliopause mission using a combination of solar/radioisotope electric propulsion
(2011)
There is common agreement within the scientific community that in order to understand our local galactic environment it will be necessary to send a spacecraft into the region beyond the solar wind termination shock. Considering distances of 200 AU for a new mission, one needs a spacecraft travelling at a speed of close to 10 AU/yr in order to keep the mission duration in the range of less than 25 yrs, a transfer time postulated by ESA.Two propulsion options for the mission have been proposed and discussed so far: the solar sail propulsion and the ballistic/radioisotope electric propulsion. As a further alternative, we here investigate a combination of solar-electric propulsion and radioisotope-electric propulsion. The solar-electric propulsion stage consists of six 22 cm diameter “RIT-22”ion thrusters working with a high specific impulse of 7377 s corresponding to a positive grid voltage of 5 kV. Solar power of 53 kW BOM is provided by a light-weight solar array. The REP-stage consists of four space-proven 10 cm diameter “RIT-10” ion thrusters that will be operating one after the other for 9 yrs in total. Four advanced radioisotope generators provide 648 W at BOM. The scientific instrument package is oriented at earlier studies. For its mass and electric power requirement 35 kg and 35 W are assessed, respectively. Optimized trajectory calculations, treated in a separate contribution, are based on our “InTrance” method.The program yields a burn out of the REP stage in a distance of 79.6 AU for a usage of 154 kg of Xe propellant. With a C3 = 45,1 (km/s)2 a heliocentric probe velocity of 10 AU/yr is reached at this distance, provided a close Jupiter gravity assist adds a velocity increment of 2.7 AU/yr. A transfer time of 23.8 yrs results for this scenario requiring about 450 kg Xe for the SEP stage, jettisoned at 3 AU. We interpret the SEP/REP propulsion as a competing alternative to solar sail and ballistic/REP propulsion. Omiting a Jupiter fly-by even allows more launch flexibility, leaving the mission duration in the range of the ESA specification.
Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper “Human Physiology – Musculoskeletal system”, this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback.
A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions
(2019)
Einschränkung von Taluskippung und -vorschub durch Sprunggelenkorthesen nach fibularer Bandruptur
(2013)
Die fibulare Bandruptur zählt zu einer der am häufigsten auftretenden Verletzungen des
Bewegungsapparats. In den meisten Fällen wird heute die konservativ frühfunktionelle Therapie mit Sprunggelenkorthesen allgemein bevorzugt. Im Rahmen der vorliegenden Studie wurden 14 verschiedene Sprunggelenkorthesen im Hinblick auf ihre Einschränkung von Taluskippung und Talusvorschub
untersucht. Zur Simulation einer fibularen Bandruptur wurde ein Unterschenkelmodell aus Holz mit Fußteil, mit angelegten Orthesen in einen Scheuba-Halteapparat eingespannt und mit 150 N seitlich sowie anterior-posterior belastet. Anhand der erstellten "gehaltenen" Röntgenaufnahmen konnten Taluskippung und Talusvorschub jeder einzelnen Orthese eindeutig bestimmt werden. Die meisten Orthesen erreichten zufriedenstellende Ergebnisse. Es stellte sich heraus, dass vor allem eine eng anliegende, im Gelenkbereich anatomisch angepasste Form vorteilhaft zu sein scheint.
Originalausgabe: Orthopädische Praxis Jg. 47. 2011 H. 11; S. 536-543. Mit freundlicher Genehmigung des Verlags Zusammenfassung: Auf der Basis von Patientenabfragen mittels Fragebogen zum Schmerzempfinden und zur Einschränkung bei Aktivitäten des alltäglichen Lebens wird die Langzeitwirkung der MBST® KernspinResonanz-Therapie bei Gonarthrose untersucht. An der Studie nahmen 39 Patienten teil, bei denen die Therapie bis zu vier Jahre zurückliegt. Neben einer Gesamtbetrachtung wird der Erfolg auch in Abhängigkeit von Alter, Geschlecht und sportlicher Aktivität analysiert. Insgesamt weist die Studie auf eine anhaltende Verbesserung des Gesundheitszustands mit zum Teil deutlicher Schmerzlinderung auch noch nach vier Jahren hin, jedoch mit einer leichten Schmerzzunahme gegen Ende des Untersuchungszeitraums von vier Jahren. Eine tendenziell positivere Wirkung bei Frauen, älteren Menschen oder auch sportlich nicht-aktiven Patienten lässt auf eine mögliche Beeinflussung des Erfolgs der Therapie durch (Über-)Belastung im Alltag schließen. Ein zusätzlich positiver Effekt der Therapie auf die Knochendichte ist ebenfalls denkbar, dies bleibt jedoch offen.
Analysis of the long-term effect of the MBST® nuclear magnetic resonance therapy on gonarthrosis
(2016)
Introduction
In regard of surgical training, the reproducible simulation of life-like proximal humerus fractures in human cadaveric specimens is desirable. The aim of the present study was to develop a technique that allows simulation of realistic proximal humerus fractures and to analyse the influence of rotator cuff preload on the generated lesions in regards of fracture configuration.
Materials and methods
Ten cadaveric specimens (6 left, 4 right) were fractured using a custom-made drop-test bench, in two groups. Five specimens were fractured without rotator cuff preload, while the other five were fractured with the tendons of the rotator cuff preloaded with 2 kg each. The humeral shaft and the shortened scapula were potted. The humerus was positioned at 90° of abduction and 10° of internal rotation to simulate a fall on the elevated arm. In two specimens of each group, the emergence of the fractures was documented with high-speed video imaging. Pre-fracture radiographs were taken to evaluate the deltoid-tuberosity index as a measure of bone density. Post-fracture X-rays and CT scans were performed to define the exact fracture configurations. Neer’s classification was used to analyse the fractures.
Results
In all ten cadaveric specimens life-like proximal humerus fractures were achieved. Two III-part and three IV-part fractures resulted in each group. The preloading of the rotator cuff muscles had no further influence on the fracture configuration. High-speed videos of the fracture simulation revealed identical fracture mechanisms for both groups. We observed a two-step fracture mechanism, with initial impaction of the head segment against the glenoid followed by fracturing of the head and the tuberosities and then with further impaction of the shaft against the acromion, which lead to separation of the tuberosities.
Conclusion
A high energetic axial impulse can reliably induce realistic proximal humerus fractures in cadaveric specimens. The preload of the rotator cuff muscles had no influence on initial fracture configuration. Therefore, fracture simulation in the proximal humerus is less elaborate. Using the presented technique, pre-fractured specimens are available for real-life surgical education.
Autonomous robotic systems for penetrating thick ice shells with simultaneous collecting of scientific data are very promising devices in both terrestrial (glacier, climate research) and extra-terrestrial applications. Technical challenges in development of such systems are numerous and include 3D-navigation, an appropriate energy source, motion control, etc. Not less important is the problem of forward contamination of the pristine glacial environments with microorganisms and biomolecules from the surface of the probe. This study was devoted to establishing a laboratory model for microbial contamination of a newly constructed ice-melting probe called IceMole and to analyse the viability and amount of the contaminating microorganisms as a function of distance. The used bacterial strains were Bacillus subtilis (ATCC 6051) and Escherichia coli (ATCC 11775). The main objective was development of an efficient and reliable in-situ decontamination method of the melting probe. Therefore, several chemical substances were tested in respect of their efficacy to eliminate bacteria on the surface of the melting probe at low temperature (0 - 5 °C) and at continuous dilution by melted water. Our study has shown that at least 99.9% decontamination of the IceMole can be successfully achieved by the injection of 30% (v/v) hydrogen peroxide and 3% (v/v) sodium hypochlorite into the drilling site. We were able to reproduce this result in both time-dependent and depth-dependent experiments. The sufficient amount of 30% (v/v) H₂O₂ or 3% (v/v) NaClO has been found to be approximately 18 L per cm² of the probe’s surface.
False spectra formation in the differential two-channel scheme of the laser Doppler flowmeter
(2018)
Noise in the differential two-channel scheme of a classic laser Doppler flowmetry (LDF) instrument was studied. Formation of false spectral components in the output signal due to beating of electrical signals in the differential amplifier was found out. The improved block-diagram of the flowmeter was developed allowing to reduce the noise.
Bilaterale stromale Hornhauttrübungen sind für den Augenarzt eine differenzialdiagnostische Herausforderung. Im folgenden Beitrag werden 2 Patieninnen (30 und 36 Jahre) mit unterschiedlich stark ausgeprägter stromaler diffuser Hornhauttrübung vorgestellt. Patientin 1 war kleinwüchsig (114 cm) und Patientin 2 normal groß (172 cm). Beide Patientinnen wiesen veränderte Gelenkstrukturen an Hand und Fußgelenken sowie diffuse stromale Hornhauttrübungen auf. Des Weiteren lagen eine Mitral- und Aorteninsuffizienz (Patientin 1) bzw. eine Aorteninsuffizienz (Patientin 2) vor. Die stromalen diffusen Hornhauttrübungen ließen im Zusammenhang mit den Gelenkveränderungen ein Scheie-Syndrom vermuten. Therapeutisch ist bei Patienten mit Visusminderung eine (lamelläre) Keratoplastik sinnvoll.
An optimization method is developed to describe the mechanical behaviour of the human cancellous bone. The method is based on a mixture theory. A careful observation of the behaviour of the bone material leads to the hypothesis that the bone density is controlled by the principal stress trajectories (Wolff’s law). The basic idea of the developed method is the coupling of a scalar value via an eigenvalue problem to the principal stress trajectories. On the one hand this theory will permit a prediction of the reaction of the biological bone structure after the implantation of a prosthesis, on the other hand it may be useful in engineering optimization problems. An analytical example shows its efficiency.
The CellDrum technology (The term 'CellDrum technology' includes a couple of slightly different technological setups for measuring lateral mechanical tension in various types of cell monolayers or 3D-tissue constructs) was designed to quantify the contraction rate and mechanical tension of self-exciting cardiac myocytes. Cells were grown either within flexible, circular collagen gels or as monolayer on top of respective 1-mum thin silicone membranes. Membrane and cells were bulged outwards by air pressure. This biaxial strain distribution is rather similar the beating, blood-filled heart. The setup allowed presetting the mechanical residual stress level externally by adjusting the centre deflection, thus, mimicking hypertension in vitro. Tension was measured as oscillating differential pressure change between chamber and environment. A 0.5-mm thick collagen-cardiac myocyte tissue construct induced after 2 days of culturing (initial cell density 2 x 10(4) cells/ml), a mechanical tension of 1.62 +/- 0.17 microN/mm(2). Mechanical load is an important growth regulator in the developing heart, and the orientation and alignment of cardiomyocytes is stress sensitive. Therefore, it was necessary to develop the CellDrum technology with its biaxial stress-strain distribution and defined mechanical boundary conditions. Cells were exposed to strain in two directions, radially and circumferentially, which is similar to biaxial loading in real heart tissues. Thus, from a biomechanical point of view, the system is preferable to previous setups based on uniaxial stretching.
All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models.
Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.
Background
Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.
Methods
In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).
Measurements and main results
PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.
Conclusion
Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.
The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.
Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.
Purpose: Image analysis by the retinal vessel analyzer (RVA) observes retinal vessels in their dynamic state online noninvasively along a chosen vessel segment. It has been found that high-frequency diameter changes in the retinal artery blood column along the vessel increase significantly in anamnestically healthy volunteers with increasing age and in patients with glaucoma during vascular dilation. This study was undertaken to investigate whether longitudinal sections of the retinal artery blood column are altered in systemic hypertension.
Methods: Retinal arteries of 15 untreated patients with essential arterial hypertension (age, 50.9 ± 11.9 years) and of 15 age-matched anamnestically healthy volunteers were examined by RVA. After baseline assessment, a monochromatic luminance flicker (530–600 nm; 12.5 Hz; 20 s) was applied to evoke retinal vasodilation. Differences in amplitude and frequency of spatial artery blood column diameter change along segments (longitudinal arterial profiles) of 1 mm in length were measured and analyzed using Fourier transformation.
Results: In the control group, average reduced power spectra (ARPS) of longitudinal arterial profiles did not differ when arteries changed from constriction to dilation. In the systemic hypertension group, ARPS during constriction, baseline, and restoration were identical and differed from ARPS during dilation (P < 0.05). Longitudinal arterial profiles in both groups showed significant dissimilitude at baseline and restoration (P < 0.05).
Conclusions: The retinal artery blood column demonstrates microstructural alterations in systemic hypertension and is less irregular along the vessel axis during vessel dilation. These microstructural changes may be an indication of alterations in vessel wall rigidity, vascular endothelial function, and smooth muscle cells in this disease, leading to impaired perfusion and regulation.
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.
Can vascular function be assessed by the interpretation of retinal vascular diameter changes?
(2011)
Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.
Hintergrund
Die Anwendung und das Verständnis von Statistik sind sehr wichtig für die biomedizinische Forschung und für die klinische Praxis. Dies gilt insbesondere auch zur Abschätzung der Möglichkeiten unterschiedlichster Diagnostik- und Therapieoptionen beim Glaukom. Die scheinbare Komplexität der Statistik, die zum Teil dem „gesunden Menschenverstand“ zu widersprechen scheint, zusammen mit der nur vorsichtigen Akzeptanz der Statistik bei vielen Medizinern können zu bewussten und unbewussten Manipulationen bei der Datendarstellung und -interpretation führen.
Ziel der Arbeit
Ziel ist die verständliche Darstellung einiger typischer Fehler in der medizinisch-statistischen Datenbehandlung.
Material und Methoden
Anhand hypothetischer Beispiele aus der Glaukomdiagnostik erfolgen die Darstellung der Wirkung eines hypotensiven Medikamentes sowie die Beurteilung der Ergebnisse eines diagnostischen Tests. Es werden die typischsten statistischen Einsatzbereiche und Irrtumsquellen ausführlich und verständlich analysiert
Ergebnisse
Mechanismen von Datenmanipulation und falscher Dateninterpretation werden aufgeklärt. Typische Irrtumsquellen bei der statistischen Auswertung und Datendarstellung werden dabei erläutert.
Schlussfolgerungen
Die erläuterten praktischen Beispiele zeigen die Notwendigkeit, die Grundlagen der Statistik zu verstehen und korrekt anwenden zu können. Fehlendes Grundlagenwissen und Halbwissen der medizinischen Statistik können zu folgenschweren Missverständnissen und falschen Entscheidungen in der medizinischen Forschung, aber auch in der klinischen Praxis führen.
Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer’s disease
(2017)
The term ocular rigidity is widely used in clinical ophthalmology. Generally it is assumed as a resistance of the whole eyeball to mechanical deformation and relates to biomechanical properties of the eye and its tissues. Basic principles and formulas for clinical tonometry, tonography and pulsatile ocular blood flow measurements are based on the concept of ocular rigidity. There is evidence for altered ocular rigidity in aging, in several eye diseases and after eye surgery. Unfortunately, there is no consensual view on ocular rigidity: it used to make a quite different sense for different people but still the same name. Foremost there is no clear consent between biomechanical engineers and ophthalmologists on the concept. Moreover ocular rigidity is occasionally characterized using various parameters with their different physical dimensions. In contrast to engineering approach, clinical approach to ocular rigidity claims to characterize the total mechanical response of the eyeball to its deformation without any detailed considerations on eye morphology or material properties of its tissues. Further to the previous chapter this section aims to describe clinical approach to ocular rigidity from the perspective of an engineer in an attempt to straighten out this concept, to show its advantages, disadvantages and various applications.
In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live–dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.
Production and Characterization of Porous Fibroin Scaffolds for Regenerative Medical Application
(2019)
Robotergestütztes System für ein verbessertes neuromuskuläres Aufbautraining der Beinstrecker
(2016)
Neuromuskuläres Aufbautraining der Beinstrecker ist ein wichtiger Bestandteil in der Rehabilitation und Prävention von Muskel-Skelett-Erkrankungen. Effektives Training erfordert hohe Muskelkräfte, die gleichzeitig hohe Belastungen von bereits geschädigten Strukturen bedeuten. Um trainingsinduzierte Schädigungen zu vermeiden, müssen diese Kräfte kontrolliert werden. Mit heutigen Trainingsgeräten können diese Ziele allerdings nicht erreicht werden. Für ein sicheres und effektives Training sollen durch den Einsatz der Robotik, Sensorik, eines Regelkreises sowie Muskel-Skelett-Modellen Belastungen am Zielgewebe direkt berechnet und kontrolliert werden. Auf Basis zweier Vorstudien zu möglichen Stellgrößen wird der Aufbau eines robotischen Systems vorgestellt, das sowohl für Forschungszwecke als auch zur Entwicklung neuartiger Trainingsgeräte verwendet werden kann.
Background and Objective
Effective leg extension training at a leg press requires high forces, which need to be controlled to avoid training-induced damage. In order to avoid high external knee adduction moments, which are one reason for unphysiological loadings on knee joint structures, both training movements and the whole reaction force vector need to be observed. In this study, the applicability of lateral and medial changes in foot orientation and position as possible manipulated variables to control external knee adduction moments is investigated. As secondary parameters both the medio-lateral position of the center of pressure and the frontal-plane orientation of the reaction force vector are analyzed.
Methods
Knee adduction moments are estimated using a dynamic model of the musculoskeletal system together with the measured reaction force vector and the motion of the subject by solving the inverse kinematic and dynamic problem. Six different foot conditions with varying positions and orientations of the foot in a static leg press are evaluated and compared to a neutral foot position.
Results
Both lateral and medial wedges under the foot and medial and lateral shifts of the foot can influence external knee adduction moments in the presented study with six healthy subjects. Different effects are observed with the varying conditions: the pose of the leg is changed and the direction and center of pressure of the reaction force vector is influenced. Each effect results in a different direction or center of pressure of the reaction force vector.
Conclusions
The results allow the conclusion that foot position and orientation can be used as manipulated variables in a control loop to actively control knee adduction moments in leg extension training.
Der vorliegende Artikel fokussiert sich auf die weibliche Belastungsinkontinenz als Insuffizienz der Speicherfunktion der Blase, auch wenn im klinischen Alltag die Harninkontinenz der Frau häufig verschiedene Ursachen hat und insbesondere eine Belastungsinkontinenz im Alter und bei neurologischer Komorbidität nur selten isoliert vorkommt.
Das kleine Becken der Frau ist sowohl als Funktions- als auch als strukturelle Einheit zu betrachten. Dabei unterliegen bei der Frau Blase, Harnröhre, Gebärmutter und Enddarm sowie die muskulären und ligamentösen Strukturen des kleinen Beckens durch Fertilitätsphase, mögliche Schwangerschaften, Geburten und Menopausen-Phase, über das „normale Altern“ hinaus, gravierenden Veränderungen.
This article focuses on female stress incontinence in the form of pelvic floor dysfunction and urethral sphincter deficiency, although isolated stress incontinence accounts for less than half of all incontinence cases. Especially in women of old age and those with neurological comorbidities, the causes of incontinence are mostly multifactorial. Also it has to be considered that the female bladder, urethra, uterus and rectum as well as the muscular and ligamentous structures of the female pelvis minor are affected by phases of fertility, possible pregnancies, births and menopause in addition to the normal ageing process.
Combining physiological relevance and throughput for in vitro cardiac contractility measurement
(2020)
Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these.
Successful bone sawing requires a high level of skill and experience, which could be gained by the use of Virtual Reality-based simulators. A key aspect of these medical simulators is realistic force feedback. The aim of this paper is to model the bone sawing process in order to develop a valid training simulator for the bilateral sagittal split osteotomy, the most often applied corrective surgery in case of a malposition of the mandible. Bone samples from a human cadaveric mandible were tested using a designed experimental system. Image processing and statistical analysis were used for the selection of four models for the bone sawing process. The results revealed a polynomial dependency between the material removal rate and the applied force. Differences between the three segments of the osteotomy line and between the cortical and cancellous bone were highlighted.