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BACKGROUND
Immunosuppression is often considered as an indication for antibiotic prophylaxis to prevent surgical site infections (SSI) while performing skin surgery. However, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited.
PATIENTS AND METHODS
All patients of the Department of Dermatology and Allergology at the University Hospital of RWTH Aachen in Aachen, Germany, who underwent hospitalization for a dermatologic surgery between June 2016 and January 2017 (6 months), were followed up after surgery until completion of the wound healing process. The follow-up addressed the occurrence of SSI and the need for systemic antibiotics after the operative procedure. Immunocompromised patients were compared with immunocompetent patients. The investigation was conducted as a retrospective analysis of patient records.
RESULTS
The authors performed 284 dermatologic surgeries in 177 patients. Nineteen percent (54/284) of the skin surgery was performed on immunocompromised patients. The most common indications for surgical treatment were nonmelanoma skin cancer and malignant melanomas. Surgical site infections occurred in 6.7% (19/284) of the cases. In 95% (18/19), systemic antibiotic treatment was needed. Twenty-one percent of all SSI (4/19) were seen in immunosuppressed patients.
CONCLUSION
According to the authors' data, immunosuppression does not represent a significant risk factor for SSI after dermatologic surgery. However, larger prospective studies are needed to make specific recommendations on the use of antibiotic prophylaxis while performing skin surgery in these patients.
The available data on complications after dermatologic surgery have improved over the past years. Particularly, additional risk factors have been identified for surgical site infections (SSI). Purulent surgical sites, older age, involvement of head, neck, and acral regions, and also the involvement of less experienced surgeons have been reported to increase the risk of the SSI after dermatologic surgeries.1 In general, the incidence of SSI after skin surgery is considered to be low.1,2 However, antibiotics in dermatologic surgeries, especially in the perioperative setting, seem to be overused,3,4 particularly regarding developing antibiotic resistances and side effects.
Immunosuppression has been recommended to be taken into consideration as an additional indication for antibiotic prophylaxis to prevent SSI after skin surgery in special cases.5,6 However, these recommendations do not specify the exact dermatologic surgeries, and were not specifically developed for dermatologic surgery patients and treatments, but adopted from other surgical fields.6 According to the survey conducted on American College of Mohs Surgery members in 2012, 13% to 29% of the surgeons administered antibiotic prophylaxis to immunocompromised patients to prevent SSI while performing dermatologic surgery on noninfected skin,3 although this was not recommended by Journal of the American Academy of Dermatology Advisory Statement. Indeed, the data on the risk of developing SSI after dermatologic surgery in immunosuppressed patients are limited. However, it is possible that due to the insufficient evidence on the risk of SSI occurrence in this patient group, dermatologic surgeons tend to overuse perioperative antibiotic prophylaxis.
To make specific recommendations on the use of antibiotic prophylaxis in immunosuppressed patients in the field of skin surgery, more information about the incidence of SSI after dermatologic surgery in these patients is needed. The aim of this study was to fill this data gap by investigating whether there is an increased risk of SSI after skin surgery in immunocompromised patients compared with immunocompetent patients.
Comparison of different training algorithms for the leg extension training with an industrial robot
(2018)
In the past, different training scenarios have been developed and implemented on robotic research platforms, but no systematic analysis and comparison have been done so far. This paper deals with the comparison of an isokinematic (motion with constant velocity) and an isotonic (motion against constant weight) training algorithm. Both algorithms are designed for a robotic research platform consisting of a 3D force plate and a high payload industrial robot, which allows leg extension training with arbitrary six-dimensional motion trajectories. In the isokinematic as well as the isotonic training algorithm, individual paths are defined i n C artesian s pace by sufficient s upport p oses. I n t he i sotonic t raining s cenario, the trajectory is adapted to the measured force as the robot should only move along the trajectory as long as the force applied by the user exceeds a minimum threshold. In the isotonic training scenario however, the robot’s acceleration is a function of the force applied by the user. To validate these findings, a simulative experiment with a simple linear trajectory is performed. For this purpose, the same force path is applied in both training scenarios. The results illustrate that the algorithms differ in the force dependent trajectory adaption.
During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation.
A capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples.
Purpose
In vivo, a loss of mesh porosity triggers scar tissue formation and restricts functionality. The purpose of this study was to evaluate the properties and configuration changes as mesh deformation and mesh shrinkage of a soft mesh implant compared with a conventional stiff mesh implant in vitro and in a porcine model.
Material and Methods
Tensile tests and digital image correlation were used to determine the textile porosity for both mesh types in vitro. A group of three pigs each were treated with magnetic resonance imaging (MRI) visible conventional stiff polyvinylidene fluoride meshes (PVDF) or with soft thermoplastic polyurethane meshes (TPU) (FEG Textiltechnik mbH, Aachen, Germany), respectively. MRI was performed with a pneumoperitoneum at a pressure of 0 and 15 mmHg, which resulted in bulging of the abdomen. The mesh-induced signal voids were semiautomatically segmented and the mesh areas were determined. With the deformations assessed in both mesh types at both pressure conditions, the porosity change of the meshes after 8 weeks of ingrowth was calculated as an indicator of preserved elastic properties. The explanted specimens were examined histologically for the maturity of the scar (collagen I/III ratio).
Results
In TPU, the in vitro porosity increased constantly, in PVDF, a loss of porosity was observed under mild stresses. In vivo, the mean mesh areas of TPU were 206.8 cm2 (± 5.7 cm2) at 0 mmHg pneumoperitoneum and 274.6 cm2 (± 5.2 cm2) at 15 mmHg; for PVDF the mean areas were 205.5 cm2 (± 8.8 cm2) and 221.5 cm2 (± 11.8 cm2), respectively. The pneumoperitoneum-induced pressure increase resulted in a calculated porosity increase of 8.4% for TPU and of 1.2% for PVDF. The mean collagen I/III ratio was 8.7 (± 0.5) for TPU and 4.7 (± 0.7) for PVDF.
Conclusion
The elastic properties of TPU mesh implants result in improved tissue integration compared to conventional PVDF meshes, and they adapt more efficiently to the abdominal wall. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 827–833, 2018.
We propose a stochastic programming method to analyse limit and shakedown of structures under random strength with lognormal distribution. In this investigation a dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit or the shakedown limit. The edge-based smoothed finite element method (ES-FEM) using three-node linear triangular elements is used.
The overall objective of this study is to develop a new external fixator, which closely maps the native kinematics of the elbow to decrease the joint force resulting in reduced rehabilitation time and pain. An experimental setup was designed to determine the native kinematics of the elbow during flexion of cadaveric arms. As a preliminary study, data from literature was used to modify a published biomechanical model for the calculation of the joint and muscle forces. They were compared to the original model and the effect of the kinematic refinement was evaluated. Furthermore, the obtained muscle forces were determined in order to apply them in the experimental setup. The joint forces in the modified model differed slightly from the forces in the original model. The muscle force curves changed particularly for small flexion angles but their magnitude for larger angles was consistent.
Pelvic floor dysfunction (PFD) is characterized by the failure of the levator ani (LA) muscle to maintain the pelvic hiatus, resulting in the descent of the pelvic organs below the pubococcygeal line. This chapter adopts the modified Humphrey material model to consider the effect of the muscle fiber on passive stretching of the LA muscle. The deformation of the LA muscle subjected to intra-abdominal pressure during Valsalva maneuver is compared with the magnetic resonance imaging (MRI) examination of a nulliparous female. Numerical result shows that the fiber-based Humphrey model simulates the muscle behavior better than isotropic constitutive models. Greater posterior movement of the LA muscle widens the levator hiatus due to lack of support from the anococcygeal ligament and the perineal structure as a consequence of birth-related injury and aging. Old and multiparous females with uncontrolled urogenital and rectal hiatus tend to develop PFDs such as prolapse and incontinence.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.
The light-addressable potentiometric sensor (LAPS) and scanning photo-induced impedance microscopy (SPIM) are two closely related methods to visualise the distributions of chemical species and impedance, respectively, at the interface between the sensing surface and the sample solution. They both have the same field-effect structure based on a semiconductor, which allows spatially resolved and label-free measurement of chemical species and impedance in the form of a photocurrent signal generated by a scanning light beam. In this article, the principles and various operation modes of LAPS and SPIM, functionalisation of the sensing surface for measuring various species, LAPS-based chemical imaging and high-resolution sensors based on silicon-on-sapphire substrates are described and discussed, focusing on their technical details and prospective applications.
A chip-based amperometric biosensor referring on using the bioelectrocatalytical amplification principle for the detection of low adrenaline concentrations is presented. The adrenaline biosensor has been prepared by modification of a platinum thin-film electrode with an enzyme membrane containing the pyrroloquinoline quinone-dependent glucose dehydrogenase and glutaraldehyde. Measuring conditions such as temperature, pH value, and glucose concentration have been optimized to achieve a high sensitivity and a low detection limit of about 1 nM adrenaline measured in phosphate buffer at neutral pH value. The response of the biosensor to different catecholamines has also been proven. Long-term stability of the adrenaline biosensor has been studied over 10 days. In addition, the biosensor has been successfully applied for adrenaline detection in human blood plasma for future biomedical applications. Furthermore, preliminary experiments have been carried to detect the adrenaline-concentration difference measured in peripheral blood and adrenal venous blood, representing the adrenal vein sampling procedure of a physician.
Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries.
The presentation of enzymes on viral scaffolds has beneficial effects such as an increased enzyme loading and a prolonged reusability in comparison to conventional immobilization platforms. Here, we used modified tobacco mosaic virus (TMV) nanorods as enzyme carriers in penicillin G detection for the first time. Penicillinase enzymes were conjugated with streptavidin and coupled to TMV rods by use of a bifunctional biotin-linker. Penicillinase-decorated TMV particles were characterized extensively in halochromic dye-based biosensing. Acidometric analyte detection was performed with bromcresol purple as pH indicator and spectrophotometry. The TMV-assisted sensors exhibited increased enzyme loading and strongly improved reusability, and higher analysis rates compared to layouts without viral adapters. They extended the half-life of the sensors from 4 - 6 days to 5 weeks and thus allowed an at least 8-fold longer use of the sensors. Using a commercial budget-priced penicillinase preparation, a detection limit of 100 µM penicillin was obtained. Initial experiments also indicate that the system may be transferred to label-free detection layouts.
Nanotubular tobacco mosaic virus (TMV) particles and RNA-free lower-order coat protein (CP) aggregates have been employed as enzyme carriers in different diagnostic layouts and compared for their influence on biosensor performance. In the following, we describe a label-free electrochemical biosensor for improved glucose detection by use of TMV adapters and the enzyme glucose oxidase (GOD). A specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CP aggregates was achieved via bioaffinity binding. Glucose sensors with adsorptively immobilized [SA]-GOD, and with [SA]-GOD cross-linked with glutardialdehyde, respectively, were tested in parallel on the same sensor chip. Comparison of these sensors revealed that TMV adapters enhanced the amperometric glucose detection remarkably, conveying highest sensitivity, an extended linear detection range and fastest response times. These results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for applications in biosensorics and biochips. Here, we describe the fabrication and use of amperometric sensor chips combining an array of circular Pt electrodes, their loading with GOD-modified TMV nanotubes (and other GOD immobilization methods), and the subsequent investigations of the sensor performance.
The inverse scattering problem for a conductive boundary condition and transmission eigenvalues
(2018)
In this paper, we consider the inverse scattering problem associated with an inhomogeneous media with a conductive boundary. In particular, we are interested in two problems that arise from this inverse problem: the inverse conductivity problem and the corresponding interior transmission eigenvalue problem. The inverse conductivity problem is to recover the conductive boundary parameter from the measured scattering data. We prove that the measured scatted data uniquely determine the conductivity parameter as well as describe a direct algorithm to recover the conductivity. The interior transmission eigenvalue problem is an eigenvalue problem associated with the inverse scattering of such materials. We investigate the convergence of the eigenvalues as the conductivity parameter tends to zero as well as prove existence and discreteness for the case of an absorbing media. Lastly, several numerical and analytical results support the theory and we show that the inside–outside duality method can be used to reconstruct the interior conductive eigenvalues.
The paper deals with the asymptotic behaviour of estimators, statistical tests and confidence intervals for L²-distances to uniformity based on the empirical distribution function, the integrated empirical distribution function and the integrated empirical survival function. Approximations of power functions, confidence intervals for the L²-distances and statistical neighbourhood-of-uniformity validation tests are obtained as main applications. The finite sample behaviour of the procedures is illustrated by a simulation study.
Field-effect-based electrolyte-insulator-semiconductor (EIS) sensors were modified with a bilayer of positively charged weak polyelectrolyte (poly(allylamine hydrochloride) (PAH)) and probe single-stranded DNA (ssDNA) and are used for the detection of complementary single-stranded target DNA (cDNA) in different test solutions. The sensing mechanism is based on the detection of the intrinsic molecular charge of target cDNA molecules after the hybridization event between cDNA and immobilized probe ssDNA. The test solutions contain synthetic cDNA oligonucleotides (with a sequence of tuberculosis mycobacteria genome) or PCR-amplified DNA (which origins from a template DNA strand that has been extracted from Mycobacterium avium paratuberculosis-spiked human sputum samples), respectively. Sensor responses up to 41 mV have been measured for the test solutions with DNA, while only small signals of ∼5 mV were detected for solutions without DNA. The lower detection limit of the EIS sensors was ∼0.3 nM, and the sensitivity was ∼7.2 mV/decade. Fluorescence experiments using SybrGreen I fluorescence dye support the electrochemical results.
A nonparametric goodness-of-fit test for random variables with values in a separable Hilbert space is investigated. To verify the null hypothesis that the data come from a specific distribution, an integral type test based on a Cramér-von-Mises statistic is suggested. The convergence in distribution of the test statistic under the null hypothesis is proved and the test's consistency is concluded. Moreover, properties under local alternatives are discussed. Applications are given for data of huge but finite dimension and for functional data in infinite dimensional spaces. A general approach enables the treatment of incomplete data. In simulation studies the test competes with alternative proposals.
In this work, a cell-based biosensor to evaluate the sterilization efficacy of hydrogen peroxide vapor sterilization processes is characterized. The transducer of the biosensor is based on interdigitated gold electrodes fabricated on an inert glass substrate. Impedance spectroscopy is applied to evaluate the sensor behavior and the alteration of test microorganisms due to the sterilization process. These alterations are related to changes in relative permittivity and electrical conductivity of the bacterial spores. Sensor measurements are conducted with and without bacterial spores (Bacillus atrophaeus), as well as after an industrial sterilization protocol. Equivalent two-dimensional numerical models based on finite element method of the periodic finger structures of the interdigitated gold electrodes are designed and validated using COMSOL® Multiphysics software by the application of known dielectric properties. The validated models are used to compute the electrical properties at different sensor states (blank, loaded with spores, and after sterilization). As a final result, we will derive and tabulate the frequency-dependent electrical parameters of the spore layer using a novel model that combines experimental data with numerical optimization techniques.
Sleep scoring is a necessary and time-consuming task in sleep studies. In animal models (such as mice) or in humans, automating this tedious process promises to facilitate long-term studies and to promote sleep biology as a data-driven f ield. We introduce a deep neural network model that is able to predict different states of consciousness (Wake, Non-REM, REM) in mice from EEG and EMG recordings with excellent scoring results for out-of-sample data. Predictions are made on epochs of 4 seconds length, and epochs are classified as artifactfree or not. The model architecture draws on recent advances in deep learning and in convolutional neural networks research. In contrast to previous approaches towards automated sleep scoring, our model does not rely on manually defined features of the data but learns predictive features automatically. We expect deep learning models like ours to become widely applied in different fields, automating many repetitive cognitive tasks that were previously difficult to tackle.
For pelvic floor disorders that cannot be treated with non-surgical procedures, minimally invasive surgery has become a more frequent and safer repair procedure. More than 20 million prosthetic meshes are implanted each year worldwide. The simple selection of a single synthetic mesh construction for any level and type of pelvic floor dysfunctions without adopting the design to specific requirements increase the risks for mesh related complications. Adverse events are closely related to chronic foreign body reaction, with enhanced formation of scar tissue around the surgical meshes, manifested as pain, mesh erosion in adjacent structures (with organ tissue cut), mesh shrinkage, mesh rejection and eventually recurrence. Such events, especially scar formation depend on effective porosity of the mesh, which decreases discontinuously at a critical stretch when pore areas decrease making the surgical reconstruction ineffective that further augments the re-operation costs. The extent of fibrotic reaction is increased with higher amount of foreign body material, larger surface, small pore size or with inadequate textile elasticity. Standardized studies of different meshes are essential to evaluate influencing factors for the failure and success of the reconstruction. Measurements of elasticity and tensile strength have to consider the mesh anisotropy as result of the textile structure. An appropriate mesh then should show some integration with limited scar reaction and preserved pores that are filled with local fat tissue. This chapter reviews various tissue reactions to different monofilament mesh implants that are used for incontinence and hernia repairs and study their mechanical behavior. This helps to predict the functional and biological outcomes after tissue reinforcement with meshes and permits further optimization of the meshes for the specific indications to improve the success of the surgical treatment.
An amperometric bi-enzyme biosensor based on substrate recycling principle for the amplification of the sensor signal has been developed for the detection of adrenaline in blood. Adrenaline can be used as biomarker verifying successful adrenal venous sampling procedure. The adrenaline biosensor has been realized via modification of a galvanic oxygen sensor with a bi-enzyme membrane combining a genetically modified laccase and a pyrroloquinoline quinone-dependent glucose dehydrogenase. The measurement conditions such as pH value and temperature were optimized to enhance the sensor performance. A high sensitivity and a low detection limit of about 0.5–1 nM adrenaline have been achieved in phosphate buffer at pH 7.4, relevant for measurements in blood samples. The sensitivity of the biosensor to other catecholamines such as noradrenaline, dopamine and dobutamine has been studied. Finally, the sensor has been successfully applied for the detection of adrenaline in human blood plasma.
A field-effect biosensor employing tobacco mosaic virus (TMV) particles as scaffolds for enzyme immobilization is presented. Nanotubular TMV scaffolds allow a dense immobilization of precisely positioned enzymes with retained activity. To demonstrate feasibility of this new strategy, a penicillin sensor has been developed by coupling a penicillinase with virus particles as a model system. The developed field-effect penicillin biosensor consists of an Al-p-Si-SiO₂-Ta₂O₅-TMV structure and has been electrochemically characterized in buffer solutions containing different concentrations of penicillin G. In addition, the morphology of the biosensor surface with virus particles was characterized by scanning electron microscopy and atomic force microscopy methods. The sensors possessed a high penicillin sensitivity of ~ 92 mV/dec in a nearly-linear range from 0.1 mM to 10 mM, and a low detection limit of about 50 µM. The long-term stability of the penicillin biosensor was periodically tested over a time period of about one year without any significant loss of sensitivity. The biosensor has also been successfully applied for penicillin detection in bovine milk samples.
Magnetic detection structure for Lab-on-Chip applications based on the frequency mixing technique
(2018)
A magnetic frequency mixing technique with a set of miniaturized planar coils was investigated for use with a completely integrated Lab-on-Chip (LoC) pathogen sensing system. The system allows the detection and quantification of superparamagnetic beads. Additionally, in terms of magnetic nanoparticle characterization ability, the system can be used for immunoassays using the beads as markers. Analytical calculations and simulations for both excitation and pick-up coils are presented; the goal was to investigate the miniaturization of simple and cost-effective planar spiral coils. Following these calculations, a Printed Circuit Board (PCB) prototype was designed, manufactured, and tested for limit of detection, linear response, and validation of theoretical concepts. Using the magnetic frequency mixing technique, a limit of detection of 15 µg/mL of 20 nm core-sized nanoparticles was achieved without any shielding.
Prosthetic textile implants of different shapes, sizes and polymers are used to correct the apical prolapse after hysterectomy (removal of the uterus). The selection of the implant before or during minimally invasive surgery depends on the patient’s anatomical defect, intended function after reconstruction and most importantly the surgeon’s preference. Weakness or damage of the supporting tissues during childbirth, menopause or previous pelvic surgeries may put females in higher risk of prolapse. Numerical simulations of reconstructed pelvic floor with weakened tissues and organ supported by textile product models: DynaMesh®-PRS soft, DynaMesh®-PRP soft and DynaMesh®-CESA from FEG Textiletechnik mbH, Germany are compared.
The porosity of surgical meshes makes them flexible for large elastic deformation and establishes the healing conditions of good tissue in growth. The biomechanic modeling of orthotropic and compressible materials requires new materials models and simulstaneoaus fit of deformation in the load direction as well as trannsversely to to load. This nonlinear modeling can be achieved by an optical deformation measurement. At the same time the full field deformation measurement allows the dermination of the change of porosity with deformation. Also the socalled effective porosity, which has been defined to asses the tisssue interatcion with the mesh implants, can be determined from the global deformation of the surgical meshes.
Kyphoplasty of Osteoporotic Fractured Vertebrae: A Finite Element Analysis about Two Types of Cement
(2019)
Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels
(2019)
Monitoring the cellular metabolism of bacteria in (bio)fermentation processes is crucial to control and steer them, and to prevent undesired disturbances linked to metabolically inactive microorganisms. In this context, cell-based biosensors can play an important role to improve the quality and increase the yield of such processes. This work describes the simultaneous analysis of the metabolic behavior of three different types of bacteria by means of a differential light-addressable potentiometric sensor (LAPS) set-up. The study includes Lactobacillus brevis, Corynebacterium glutamicum, and Escherichia coli, which are often applied in fermentation processes in bioreactors. Differential measurements were carried out to compensate undesirable influences such as sensor signal drift, and pH value variation during the measurements. Furthermore, calibration curves of the cellular metabolism were established as a function of the glucose concentration or cell number variation with all three model microorganisms. In this context, simultaneous (bio)sensing with the multi-organism LAPS-based set-up can open new possibilities for a cost-effective, rapid detection of the extracellular acidification of bacteria on a single sensor chip. It can be applied to evaluate the metabolic response of bacteria populations in a (bio)fermentation process, for instance, in the biogas fermentation process.
Enzyme-catalyzed reactions have been designed to mimic various Boolean logic gates in the general framework of unconventional biomolecular computing. While some of the logic gates, particularly OR, AND, are easy to realize with biocatalytic reactions and have been reported in numerous publications, some other, like NXOR, are very challenging and have not been realized yet with enzyme reactions. The paper reports on a novel approach to mimicking the NXOR logic gate using the bell-shaped enzyme activity dependent on pH values. Shifting pH from the optimum value to the acidic or basic values by using acid or base inputs (meaning 1,0 and 0,1 inputs) inhibits the enzyme reaction, while keeping the optimum pH (assuming 0,0 and 1,1 input combinations) preserves a high enzyme activity. The challenging part of the present approach is the selection of an enzyme with a well-demonstrated bell-shape activity dependence on the pH value. While many enzymes can satisfy this condition, we selected pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase as this enzyme has the optimum pH center-located on the pH scale allowing the enzyme activity change by the acidic and basic pH shift from the optimum value corresponding to the highest activity. The present NXOR gate is added to the biomolecular “toolbox” as a new example of Boolean logic gates based on enzyme reactions.
Hydrogen peroxide (H2O2) is a typical surface sterilization agent for packaging materials used in the pharmaceutical, food and beverage industries. We use the finite-elements method to analyze the conceptual design of an in-line thermal evaporation unit to produce a heated gas mixture of air and evaporated H2O2 solution. For the numerical model, the required phase-transition variables of pure H2O2 solution and of the aerosol mixture are acquired from vapor-liquid equilibrium (VLE) diagrams derived from vapor-pressure formulations. This work combines homogeneous single-phase turbulent flow with heat-transfer physics to describe the operation of the evaporation unit. We introduce the apparent heat-capacity concept to approximate the non-isothermal phase-transition process of the H2O2-containing aerosol. Empirical and analytical functions are defined to represent the temperature- and pressure-dependent material properties of the aqueous H2O2 solution, the aerosol and the gas mixture. To validate the numerical model, the simulation results are compared to experimental data on the heating power required to produce the gas mixture. This shows good agreement with the deviations below 10%. Experimental observations on the formation of deposits due to the evaporation of stabilized H2O2 solution fits the prediction made from simulation results.
Production and Characterization of Porous Fibroin Scaffolds for Regenerative Medical Application
(2019)
Neuromuscular strength training of the leg extensor muscles plays an important role in the rehabilitation and prevention of age and wealth related diseases. In this paper, we focus on the design and implementation of a Cartesian admittance control scheme for isotonic training, i.e. leg extension and flexion against a predefined weight. For preliminary testing and validation of the designed algorithm an experimental research and development platform consisting of an
industrial robot and a force plate mounted at its end-effector has been used. Linear, diagonal and arbitrary two-dimensional motion trajectories with different weights for the leg extension and flexion part are applied. The proposed algorithm is easily adaptable to trajectories consisting of arbitrary six-dimensional poses and allows the implementation of individualized trajectories.
Effective training requires high muscle forces potentially leading to training-induced injuries. Thus, continuous monitoring and controlling of the loadings applied to the musculoskeletal system along the motion trajectory is required. In this paper, a norm-optimal iterative learning control algorithm for the robot-assisted training is developed. The algorithm aims at minimizing the external knee joint moment, which is commonly used to quantify the loading of the medial compartment. To estimate the external knee joint moment, a musculoskeletal lower extremity model is implemented in OpenSim and coupled with a model of an industrial robot and a force plate mounted at its end-effector. The algorithm is tested in simulation for patients with varus, normal and valgus alignment of the knee. The results show that the algorithm is able to minimize the external knee joint moment in all three cases and converges after less than seven iterations.
The MYOTONES experiment is the first to monitor changes in the basic biomechanical properties (tone, elasticity and stiffness) of the resting human myofascial system due to microgravity with a oninvasive, portable device on board the ISS. The MyotonPRO device applies several brief mechanical stimuli to the surface of the skin, and the natural oscillation signals of the tissue beneath are detected and computed by the MyotonPRO. Thus, an objective, quick and easy determination of the state of the underlying tissue is possible.
Two preflight, four inflight and four post flight measurements were performed on a male astronaut using the same 10 measurement points (MP) for each session. MPs were located on the plantar fascia, Achilles tendon, M. soleus, M. gastrocnemius, M. multifidus, M. splenius capitis, M. deltoideus anterior, M. rectus femoris, infrapatellar tendon, M. tibialis anterior. Subcutaneous tissues thickness above the MPs was measured using ultrasound imaging. Magnetic resonance images (MRI) of lower limb muscles and functional tests were also performed pre- and postflight.
Our first measurements on board the ISS confirmed increased tone and stiffness of the lumbar multifidus muscle, an important trunk stabilizer, dysfunction of which is known to be associated with back pain. Furthermore, reduced tone and stiffness of Achilles tendon and plantar fascia were observed inflight vs. preflight, confirming previous findings from terrestrial analog studies and parabolic
flights. Unexpectedly, the deltoid showed negative inflight changes in tone and stiffness, and increased elasticity, suggesting a potential risk of muscle atrophy in longer spaceflight that should be addressed by adequate inflight countermeasure protocols. Most values from limb and back MPS showed deflected patterns (in either directions) from inflight shortly after the re-entry phase on the landing day and one week later. Most parameter values then normalized to baseline after 3 weeks likely due to 1G re-adaptation and possible outcome of the reconditioning protocol. No major changes in subcutaneous tissues thickness above the MPs were found inflight vs preflight, suggesting no bias (i.e., fluid shift, extreme tissue thickening or loss). Pre- and postflight MRI and functional tests showed negligible changes in calf muscle size, power and force, which is likely due to training effects from current inflight exercise protocols.
The MYOTONES experiment is currently ongoing to collect data from further crew members. The potential impact of this research is to better understand the effects of microgravity and countermeasures over the time course of an ISS mission cycle. This will enable exercise countermeasures to be tailored
Training-induced increase in Achilles tendon stiffness affects tendon strain pattern during running
(2019)
Background
During the stance phase of running, the elasticity of the Achilles tendon enables the utilisation of elastic energy and allows beneficial contractile conditions for the triceps surae muscles. However, the effect of changes in tendon mechanical properties induced by chronic loading is still poorly understood. We tested the hypothesis that a training-induced increase in Achilles tendon stiffness would result in reduced tendon strain during the stance phase of running, which would reduce fascicle strains in the triceps surae muscles, particularly in the mono-articular soleus.
Methods
Eleven subjects were assigned to a training group performing isometric singleleg plantarflexion contractions three times per week for ten weeks, and another ten subjects formed a control group. Before and after the training period, Achilles tendon stiffness was estimated, and muscle-tendon mechanics were assessed during running at preferred speed using ultrasonography, kinematics and kinetics.
Results
Achilles tendon stiffness increased by 18% (P <0:01) in the training group, but the associated reduction in strain seen during isometric contractions was not statistically significant. Tendon elongation during the stance phase of running was similar after training, but tendon recoil was reduced by 30% (P <0:01), while estimated tendon force remained unchanged. Neither gastrocnemius medialis nor soleus fascicle shortening during stance was affected by training.
Discussion
These results show that a training-induced increase in Achilles tendon
stiffness altered tendon behaviour during running. Despite training-induced changes in tendon mechanical properties and recoil behaviour, the data suggest that fascicle shortening patterns were preserved for the running speed that we examined. The asymmetrical changes in tendon strain patterns supports the notion that simple inseries models do not fully explain the mechanical output of the muscle-tendon unit during a complex task like running.
Postural and metabolic benefits of using a forearm support walker in older adults with impairments
(2019)
A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions
(2019)
For performing point-of-care molecular diagnostics, magnetic immunoassays constitute a promising alternative to established enzyme-linked immunosorbent assays (ELISA) because they are fast, robust and sensitive. Simultaneous detection of multiple biomolecular targets from one body fluid sample is desired. The aim of this work is to show that multiplex magnetic immunodetection based on magnetic frequency mixing by means of modular immunofiltration columns prepared for different targets is feasible. By calculations of the magnetic response signal, the required spacing between the modules was determined. Immunofiltration columns were manufactured by 3D printing and antibody immobilization was performed in a batch approach. It was shown experimentally that two different target molecules in a sample solution could be individually detected in a single assaying step with magnetic measurements of the corresponding immobilization filters. The arrangement order of the filters and of a negative control did not influence the results. Thus, a simple and reliable approach to multi-target magnetic immunodetection was demonstrated.
The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.
Suppose we have k samples X₁,₁,…,X₁,ₙ₁,…,Xₖ,₁,…,Xₖ,ₙₖ with different sample sizes ₙ₁,…,ₙₖ and unknown underlying distribution functions F₁,…,Fₖ as observations plus k families of distribution functions {G₁(⋅,ϑ);ϑ∈Θ},…,{Gₖ(⋅,ϑ);ϑ∈Θ}, each indexed by elements ϑ from the same parameter set Θ, we consider the new goodness-of-fit problem whether or not (F₁,…,Fₖ) belongs to the parametric family {(G₁(⋅,ϑ),…,Gₖ(⋅,ϑ));ϑ∈Θ}. New test statistics are presented and a parametric bootstrap procedure for the approximation of the unknown null distributions is discussed. Under regularity assumptions, it is proved that the approximation works asymptotically, and the limiting distributions of the test statistics in the null hypothesis case are determined. Simulation studies investigate the quality of the new approach for small and moderate sample sizes. Applications to real-data sets illustrate how the idea can be used for verifying model assumptions.
Human induced pluripotent stem cells (hiPSCs) have shown to be promising in disease studies and drug screenings [1]. Cardiomyocytes derived from hiPSCs have been extensively investigated using patch-clamping and optical methods to compare their electromechanical behaviour relative to fully matured adult cells. Mathematical models can be used for translating findings on hiPSCCMs to adult cells [2] or to better understand the mechanisms of various ion channels when a drug is applied [3,4]. Paci et al. (2013) [3] developed the first model of hiPSC-CMs, which they later refined based on new data [3]. The model is based on iCells® (Fujifilm Cellular Dynamics, Inc. (FCDI), Madison WI, USA) but major differences among several cell lines and even within a single cell line have been found and motivate an approach for creating sample-specific models. We have developed an optimisation algorithm that parameterises the conductances (in S/F=Siemens/Farad) of the latest Paci et al. model (2018) [5] using current-voltage data obtained in individual patch-clamp experiments derived from an automated patch clamp system (Patchliner, Nanion Technologies GmbH, Munich).
The method of fundamental solutions is applied to the approximate computation of interior transmission eigenvalues for a special class of inhomogeneous media in two dimensions. We give a short approximation analysis accompanied with numerical results that clearly prove practical convenience of our alternative approach.
Hypertension describes the pathological increase of blood pressure, which is most commonly associated with the increase of vascular wall stiffness [1]. Referring to the “Deutsche Bluthochdruck Liga” this pathology shows a growing trend in our aging society. In order to find novel pharmacological and probably personalized treatments, we want to present a functional approach to study biomechanical properties of a human aortic vascular model.
In this method review we will give an overview of recent studies which were carried out with the CellDrum technology [2] and underline the added value to already existing standard procedures known from the field of physiology.
Herein described CellDrum technology is a system to measure functional mechanical properties of cell monolayers and thin tissue constructs in-vitro. Additionally, the CellDrum enables to elucidate the mechanical response of cells to pharmacological drugs, toxins and vasoactive agents. Due to its highly flexible polymer support, cells can also be mechanically stimulated by steady and cyclic biaxial stretching.
Clearance of blood components and fluid drainage play a crucial role in subarachnoid hemorrhage (SAH) and post hemorrhagic hydrocephalus (PHH). With the involvement of interstitial fluid (ISF) and cerebrospinal fluid (CSF), two pathways for the clearance of fluid and solutes in the brain are proposed. Starting at the level of capillaries, flow of ISF follows along the basement membranes in the walls of cerebral arteries out of the parenchyma to drain into the lymphatics and CSF [1]–[3]. Conversely, it is shown that CSF enters the parenchyma between glial and pial basement membranes of penetrating arteries [4]–[6]. Nevertheless, the involved structures and the contribution of either flow pathway to fluid balance between the subarachnoid space and interstitial space remains controversial. Low frequency oscillations in vascular tone are referred to as vasomotion and corresponding vasomotion waves are modeled as the driving force for flow of ISF out of the parenchyma [7]. Retinal vessel analysis (RVA) allows non-invasive measurement of retinal vessel vasomotion with respect to diameter changes [8]. Thus, the aim of the study is to investigate vasomotion in RVA signals of SAH and PHH patients.
Socio-technical scenarios for energy-intensive industries: the future of steel production in Germany
(2019)
Sensitive and rapid detection of cholera toxin subunit B using magnetic frequency mixing detection
(2019)
Cholera is a life-threatening disease caused by the cholera toxin (CT) as produced by some Vibrio cholerae serogroups. In this research we present a method which directly detects the toxin’s B subunit (CTB) in drinking water. For this purpose we performed a magnetic sandwich immunoassay inside a 3D immunofiltration column. We used two different commercially available antibodies to capture CTB and for binding to superparamagnetic beads. ELISA experiments were performed to select the antibody combination. The beads act as labels for the magnetic frequency mixing detection technique. We show that the limit of detection depends on the type of magnetic beads. A nonlinear Hill curve was fitted to the calibration measurements by means of a custom-written python software. We achieved a sensitive and rapid detection of CTB within a broad concentration range from 0.2 ng/ml to more
than 700 ng/ml.
The movement of magnetic beads due to a magnetic field gradient is of great interest in different application fields. In this report we present a technique based on a magnetic tweezers setup to measure the velocity factor of magnetically actuated individual superparamagnetic beads in a fluidic environment. Several beads can be tracked simultaneously in order to gain and improve statistics. Furthermore we show our results for different beads with hydrodynamic diameters between 200 and 1000 nm from diverse manufacturers. These measurement data can, for example, be used to determine design parameters for a magnetic separation system, like maximum flow rate and minimum separation time, or to select suitable beads for fixed experimental requirements.
In modern bioanalytical methods, it is often desired to detect several targets in one sample within one measurement. Immunological methods including those that use superparamagnetic beads are an important group of techniques for these applications. The goal of this work is to investigate the feasibility of simultaneously detecting different superparamagnetic beads acting as markers using the magnetic frequency mixing technique. The frequency of the magnetic excitation field is scanned while the lower driving frequency is kept constant. Due to the particles’ nonlinear magnetization, mixing frequencies are generated. To record their amplitude and phase information, a direct digitization of the pickup-coil’s signal with subsequent Fast Fourier Transformation is performed. By synchronizing both magnetic beads using frequency scanning in magnetic frequency mixing technique magnetic fields, a stable phase information is gained. In this research, it is shown that the amplitude of the dominant mixing component is proportional to the amount of superparamagnetic beads inside a sample. Additionally, it is shown that the phase does not show this behaviour. Excitation frequency scans of different bead types were performed, showing different phases, without correlation to their diverse amplitudes. Two commercially available beads were selected and a determination of their amount in a mixture is performed as a demonstration for multiplex measurements.
The paper deals with an asymptotic relative efficiency concept for confidence regions of multidimensional parameters that is based on the expected volumes of the confidence regions. Under standard conditions the asymptotic relative efficiencies of confidence regions are seen to be certain powers of the ratio of the limits of the expected volumes. These limits are explicitly derived for confidence regions associated with certain plugin estimators, likelihood ratio tests and Wald tests. Under regularity conditions, the asymptotic relative efficiency of each of these procedures with respect to each one of its competitors is equal to 1. The results are applied to multivariate normal distributions and multinomial distributions in a fairly general setting.
Recognition of subjects with mild cognitive impairment (MCI) by the use of retinal arterial vessels.
(2019)
A second-order L-stable exponential time-differencing (ETD) method is developed by combining an ETD scheme with approximating the matrix exponentials by rational functions having real distinct poles (RDP), together with a dimensional splitting integrating factor technique. A variety of non-linear reaction-diffusion equations in two and three dimensions with either Dirichlet, Neumann, or periodic boundary conditions are solved with this scheme and shown to outperform a variety of other second-order implicit-explicit schemes. An additional performance boost is gained through further use of basic parallelization techniques.
Purpose
The aim of this study was to compare several osteosynthesis techniques (intramedullary headless compression screws, T-plates, and Kirschner wires) for distal epiphyseal fractures of proximal phalanges in a human cadaveric model.
Methods
A total of 90 proximal phalanges from 30 specimens (index, ring, and middle fingers) were used for this study. After stripping off all soft tissue, a transverse distal epiphyseal fracture was simulated at the proximal phalanx. The 30 specimens were randomly assigned to 1 fixation technique (30 per technique), either a 3.0-mm intramedullary headless compression screw, locking plate fixation with a 2.0-mm T-plate, or 2 oblique 1.0-mm Kirschner wires. Displacement analysis (bending, distraction, and torsion) was performed using optical tracking of an applied random speckle pattern after osteosynthesis. Biomechanical testing was performed with increasing cyclic loading and with cyclic load to failure using a biaxial torsion-tension testing machine.
Results
Cannulated intramedullary compression screws showed significantly less displacement at the fracture site in torsional testing. Furthermore, screws were significantly more stable in bending testing. Kirschner wires were significantly less stable than plating or screw fixation in any cyclic load to failure test setup.
Conclusions
Intramedullary compression screws are a highly stable alternative in the treatment of transverse distal epiphyseal phalangeal fractures. Kirschner wires seem to be inferior regarding displacement properties and primary stability.
Clinical relevance
Fracture fixation of phalangeal fractures using plate osteosynthesis may have the advantage of a very rigid reduction, but disadvantages such as stiffness owing to the more invasive surgical approach and soft tissue irritation should be taken into account. Headless compression screws represent a minimally invasive choice for fixation with good biomechanical properties.
The enantioselective synthesis of α-hydroxy ketones and vicinal diols is an intriguing field because of the broad applicability of these molecules. Although, butandiol dehydrogenases are known to play a key role in the production of 2,3-butandiol, their potential as biocatalysts is still not well studied. Here, we investigate the biocatalytic properties of the meso-butanediol dehydrogenase from Bacillus licheniformis DSM 13T (BlBDH). The encoding gene was cloned with an N-terminal StrepII-tag and recombinantly overexpressed in E. coli. BlBDH is highly active towards several non-physiological diketones and α-hydroxyketones with varying aliphatic chain lengths or even containing phenyl moieties. By adjusting the reaction parameters in biotransformations the formation of either the α-hydroxyketone intermediate or the diol can be controlled.
Pressure distribution to the distal biceps tendon at the radial tuberosity: a biomechanical study
(2020)
Purpose
Mechanical impingement at the narrow radioulnar space of the tuberosity is believed to be an etiological factor in the injury of the distal biceps tendon. The aim of the study was to compare the pressure distribution at the proximal radioulnar space between 2 fixation techniques and the intact state.
Methods
Six right arms and 6 left arms from 5 female and 6 male frozen specimens were used for this study. A pressure transducer was introduced at the height of the radial tuberosity with the intact distal biceps tendon and after 2 fixation methods: the suture-anchor and the cortical button technique. The force (N), maximum pressure (kPa) applied to the radial tuberosity, and the contact area (mm²) of the radial tuberosity with the ulna were measured and differences from the intact tendon were detected from 60° supination to 60° pronation in 15° increments with the elbow in full extension and in 45° and 90° flexion of the elbow.
Results
With the distal biceps tendon intact, the pressures during pronation were similar regardless of extension and flexion and were the highest at 60° pronation with 90° elbow flexion (23.3 ± 53.5 kPa). After repair of the tendon, the mean peak pressure, contact area, and total force showed an increase regardless of the fixation technique. Highest peak pressures were found using the cortical button technique at 45° flexion of the elbow and 60° pronation. These differences were significantly different from the intact tendon. The contact area was significantly larger in full extension and 15°, 30°, and 60° pronation using the cortical button technique.
Conclusions
Pressures on the distal biceps tendon at the radial tuberosity increase during pronation, especially after repair of the tendon.
Clinical relevance
Mechanical impingement could play a role in both the etiology of primary distal biceps tendon ruptures and the complications occurring after fixation of the tendon using certain techniques.
α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716ᵀ (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn²⁺ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.