Ångstrom-Depth Resolution with Chemical Specificity at the Liquid-Vapor Interface.

The determination of depth profiles across interfaces is of primary importance in many scientific and technological areas. Photoemission spectroscopy is in principle well suited for this purpose, yet a quantitative implementation for investigations of liquid-vapor interfaces is hindered by the lack of understanding of electron-scattering processes in liquids. Previous studies have shown, however, that core-level photoelectron angular distributions (PADs) are altered by depth-dependent elastic electron scattering and can, thus, reveal information on the depth distribution of species across the interface. Here, we explore this concept further and show that the experimental anisotropy parameter characterizing the PAD scales linearly with the average distance of atoms along the surface normal obtained by molecular dynamics simulations. This behavior can be accounted for in the low-collision-number regime. We also show that results for different atomic species can be compared on the same length scale. We demonstrate that atoms separated by about 1 Å along the surface normal can be clearly distinguished with this method, achieving excellent depth resolution.

Resonant X-ray photoelectron spectroscopy: identification of atomic contributions to valence states.

Valence electronic structure is crucial for understanding and predicting reactivity. Valence non-resonant X-ray photoelectron spectroscopy (NRXPS) provides a direct method for probing the overall valence electronic structure. However, it is often difficult to separate the varying contributions to NRXPS; for example, contributions of solutes in solvents or functional groups in complex molecules. In this work we show that valence resonant X-ray photoelectron spectroscopy (RXPS) is a vital tool for obtaining atomic contributions to valence states. We combine RXPS with NRXPS and density functional theory calculations to demonstrate the validity of using RXPS to identify atomic contributions for a range of solutes (both neutral and ionic) and solvents (both molecular solvents and ionic liquids). Furthermore, the one-electron picture of RXPS holds for all of the closed shell molecules/ions studied, although the situation for an open-shell metal complex is more complicated. The factors needed to obtain a strong RXPS signal are investigated in order to predict the types of systems RXPS will work best for; a balance of element electronegativity and bonding type is found to be important. Additionally, the dependence of RXPS spectra on both varying solvation environment and varying local-covalent bonding is probed. We find that RXPS is a promising fingerprint method for identifying species in solution, due to the spectral shape having a strong dependence on local-covalency but a weak dependence on the solvation environment.

[Surgical treatment of proximal femoral fractures in high-risk geriatric patients under peripheral regional anesthesia : A clinical case series]. / Operative Versorgung hüftgelenknaher Femurfrakturen bei geriatrischen Patienten mit hohem Narkoserisiko in peripherer Regionalanästhesie : Eine klinische Fallserie.

The authors describe in a clinical case series (n = 7) of older (age 78-95 years) high-risk patients the successful surgical treatment of proximal femoral fractures in a peripheral regional anesthesia technique. After positioning on the non-fractured side, a double injection technique (dual guidance concept: sonography plus nerve stimulation) was chosen. The injections were performed parasacrally (blockade of the sacral plexus under the piriformis muscle) and lumbar-paravertebrally (psoas compartment block and transmuscular quadratus lumborum block). Per block 15 ml ropivacaine 0.5% or 20 ml ropivacaine 0.375% was administered. The total dose of 225 mg ropivacaine was never exceeded. In 5 out of 7 cases a supplemental medication with 2 times 5 µg sufentanil (n = 2) and/or 1-1.5 mg/kg body weight and h propofol (n = 4) was administered with spontaneous breathing. In addition to potential benefits, the authors also discuss limitations of the procedure, for example by the use of oral anticoagulants.

Ultrasound-guided intermediate cervical plexus and additional peripheral facial nerve block for carotid endarterectomy : A prospective pilot study.

BACKGROUND AND OBJECTIVES: Ultrasound-guided intermediate cervical plexus block with perivascular local anesthetic infiltration is an established anesthetic procedure for carotid endarterectomy. In this prospective pilot study an additional subplatysmal block of the superficial ansa cervicalis is presented for the first time. The target structures are the anastomoses between the facial nerve (cervical and marginal mandibular branches) and cervical plexus. METHODS: An ultrasound-guided intermediate cervical plexus block (20 ml of ropivacaine 0.75%) was performed (n = 28). Then, depending on the individual sonoanatomy, 5 ml of prilocaine 1% was injected into the carotid sheath (group 1: no perivascular infiltration, n = 14, group 2: perivascular infiltration, n = 14). The third step was subplatysmal injection of 5 ml of prilocaine 1% between the medial edge of the sternocleidomastoid muscle and the submandibular gland (n = 28). The investigated parameters included the need for supplementation and block-related side effects. RESULTS: The requirement for supplemental local anesthetic infiltration in the skin incision area was minimal at mean (M) 1.1 ml (standard deviation (SD) ±2.4 ml). Perivascular infiltration in group 2 significantly decreased the total amount of local anesthetic supplemented: group 1 M = 4.2 ml (SD = ±3.1 ml), group 2 M = 1.7 ml (SD = ±2.0 ml) (p = 0.018). The incidence of block-related side effects was not significantly different between the two groups. CONCLUSION: This study presents an ultrasound-guided subplatysmal block of the superficial ansa cervicalis for the first time, with the aim of optimizing anesthesia quality during surgical interventions in the carotid triangle.

Mechanical behavior of idealized, stingray-skeleton-inspired tiled composites as a function of geometry and material properties.

Tilings are constructs of repeated shapes covering a surface, common in both manmade and natural structures, but in particular are a defining characteristic of shark and ray skeletons. In these fishes, cartilaginous skeletal elements are wrapped in a surface tessellation, comprised of polygonal mineralized tiles linked by flexible joints, an arrangement believed to provide both stiffness and flexibility. The aim of this research is to use two-dimensional analytical models to evaluate the mechanical performance of stingray skeleton-inspired tessellations, as a function of their material and structural parameters. To calculate the effective modulus of modeled composites, we subdivided tiles and their surrounding joint material into simple shapes, for which mechanical properties (i.e. effective modulus) could be estimated using a modification of traditional Rule of Mixtures equations, that either assume uniform strain (Voigt) or uniform stress (Reuss) across a loaded composite material. The properties of joints (thickness, Young's modulus) and tiles (shape, area and Young's modulus) were then altered, and the effects of these tessellation parameters on the effective modulus of whole tessellations were observed. We show that for all examined tile shapes (triangle, square and hexagon) composite stiffness increased as the width of the joints was decreased and/or the stiffness of the tiles was increased; this supports hypotheses that the narrow joints and high tile to joint stiffness ratio in shark and ray cartilage optimize composite tissue stiffness. Our models also indicate that, for simple, uniaxial loading, square tessellations are least sensitive and hexagon tessellations most sensitive to changes in model parameters, indicating that hexagon tessellations are the most "tunable" to specific mechanical properties. Our models provide useful estimates for the tensile and compressive properties of 2d tiled composites under uniaxial loading. These results lay groundwork for future studies into more complex (e.g. biological) loading scenarios and three dimensional structural parameters of biological tilings, while also providing insight into the mechanical roles of tessellations in general and improving the design of bioinspired materials.

Single-Molecule Insight Into Target Recognition by CRISPR-Cas Complexes.

Ribonucleoprotein (RNP) complexes from CRISPR-Cas systems have attracted enormous interest since they can be easily and flexibly reprogrammed to target any desired locus for genome engineering and gene regulation applications. Basis for the programmability is a short RNA (crRNA) inside these complexes that recognizes the target nucleic acid by base pairing. For CRISPR-Cas systems that target double-stranded DNA this results in local DNA unwinding and formation of a so-called R-loop structure. Here we provide an overview how this target recognition mechanism can be dissected in great detail at the level of a single molecule. Specifically, we demonstrate how magnetic tweezers are applied to measure the local DNA unwinding at the target in real time. To this end we introduce the technique and the measurement principle. By studying modifications of the consensus target sequence, we show how different sequence elements contribute to the target recognition mechanism. From these data, a unified target recognition mechanism can be concluded for the RNPs Cascade and Cas9 from types I and II CRISPR-Cas systems. R-loop formation is hereby initiated on the target at an upstream element, called protospacer adjacent motif (PAM), from which the R-loop structure zips directionally toward the PAM-distal end of the target. At mismatch positions, the R-loop propagation stalls and further propagation competes with collapse of the structure. Upon full R-loop zipping conformational changes within the RNPs trigger degradation of the DNA target. This represents a shared labor mechanism in which zipping between nucleic acid strands is the actual target recognition mechanism while sensing of the R-loop arrival at the PAM-distal end just verifies the success of the full zipping.

Transarterial embolization (TAE) as add-on to percutaneous radiofrequency ablation (RFA) for the treatment of renal tumors: Review of the literature, overview of state-of-the-art embolization materials and further perspective of advanced image-guided tumor ablation.

Percutaneous radiofrequency ablation (RFA) for the treatment of stage I renal cell carcinoma has recently gained significant attention as the now available long-term and controlled data demonstrate that RFA can result in disease-free and cancer-specific survival comparable with partial and/or radical nephrectomy. In the non-controlled single center trials, however, the rates of treatment failure vary. Operator experience and ablation technique may explain some of the different outcomes. In the controlled trials, a major limitation is the lack of adequate randomization. In case reports, original series and overview articles, transarterial embolization (TAE) before percutaneous RFA was promising to increase tumor control and to reduce complications. The purpose of this study was to systematically review the literature on TAE as add-on to percutaneous RFA for renal tumors. Specific data regarding technique, tumor and patient characteristics as well as technical, clinical and oncologic outcomes have been analyzed. Additionally, an overview of state-of-the-art embolization materials and the radiological perspective of advanced image-guided tumor ablation (TA) will be discussed. In conclusion, TAE as add-on to percutaneous RFA is feasible and very effective and safe for the treatment of T1a tumors in difficult locations and T1b tumors. Advanced radiological techniques and technologies such as microwave ablation, innovative embolization materials and software-based solutions are now available, or will be available in the near future, to reduce the limitations of bland RFA. Clinical implementation is extremely important for performing image-guided TA as a highly standardized effective procedure even in the most challenging cases of localized renal tumors.

Ultrasound-guided intermediate cervical plexus block and perivascular local anesthetic infiltration for carotid endarterectomy : A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Ultrasound-guided blocks of the cervical plexus are established anesthetic procedures for carotid endarterectomy. This randomized, double-blind, placebo-controlled study tested the hypothesis that an additional ultrasound-guided periarterial injection of local anesthetic leads to a lower frequency of periarterial supplementation by the surgeon. METHODS: A total of 40 patients were randomly assigned to 1 of 2 groups. In both groups an ultrasound-guided intermediate cervical plexus block (20 ml of 0.75 % ropivacaine) at the level of the fourth cervical vertebra was performed. In a second step, the needle was inserted from posterolateral to anteromedial (in-plane technique) relative to the internal carotid artery and then, depending on the randomized group assignment, 5 ml of 0.75 % ropivacaine (group 2) or 5 ml of 0.9 % saline (group 1) was injected. The parameters investigated included the need for supplementation, patient comfort, the incidence of side effects and circulatory changes. RESULTS: The two groups did not significantly differ (p = 0.459) in terms of the need for intraoperative supplementation with 1 % prilocaine with a mean (range) in group 2 of 4.9 ml (0-20 ml), in group 1 of 3.7 ml (0-16 ml) and patient comfort (p = 0.144). In addition, a trend towards a higher complication rate was observed in group 2. CONCLUSION: For ultrasound-guided intermediate blocks of the cervical plexus, an additional periarterial infiltration showed no advantage. Abandoning this technique leads to a relevant simplification of the blocking technique and tends to reduce block-related side effects.

Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla.

PURPOSE: The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. MATERIALS AND METHODS: 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45°, TA = 1: 23 min, FOV = 5.12 × 5.12 cm(2), matrix = 256 × 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. RESULTS: Mean SNRliver (Gd-DOTA: 14.6 +/- 0.7; AGuIX: 28.2+/- 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 +/- 1.2; AGuIX: 29.6 +/- 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 +/- 0.7; AGuIX: 15.4 +/- 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 +/- 0.3; AGuIX: 14.0 +/- 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 +/- 0.2; AGuIX: -7.5 +/- 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 +/- 0.7; AGuIX: 14.9 +/- 2.8, p = 0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. CONCLUSION: AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors. KEY POINTS: AGuIX provides superior enhancement as compared to the extracellular compound Gd-DOTA at 9.4 T. AGuIX may improve the detection and diagnostic sensitivity of malignant focal liver lesions. The small size of AGuIX allows for fast renal clearance and prevents undesirable accumulation in the body.

[Ultrasound-guided intermediate cervical plexus block. Anatomical study]. / Ultraschallgesteuerte intermediäre zervikale Plexusanästhesie: Anatomische Untersuchung.

BACKGROUND AND OBJECTIVES: The innervation of the human cervical region is complex and subject to relevant anatomical variability involving sections of the cervical plexus, brachial plexus and cranial nerves. AIM: The objective was to demonstrate the dissemination of injected dye solution by anatomical preparation and to define a suitable target compartment for an ultrasound-guided block technique. MATERIAL AND METHODS: Own anatomical preparations are compared to recent review articles on the subject. The focus is on clinically relevant conclusions for performing cervical plexus blocks. In three non-embalmed cadavers six intermediate ultrasound-guided blocks of the cervical plexus were carried out, each with 20 ml methylene blue. Following preparation of the cervical plexus photographic documentation of the spread of the injected marker was performed. RESULTS: In five cases the target compartment was correctly identified. In these cases, a cranio-caudal spread of the injectate within the double layer of the cervical fascia was observed. In addition, the superficial layer was permeable to the injected methylene blue. The injection solution disseminated with the sensitive terminal branches of the cervical plexus below the platysma. In all cases an anastomosis (superficial cervical ansa) between the facial nerve (ramus colli) and the cervical plexus (transverse cervical nerve) could be demonstrated. The prevertebral lamina proved to be impermeable to injected methylene blue and no evidence of a porous structure of the prevertebral lamina was found. CONCLUSION: The compartment between the superficial and the prevertebral layer of the cervical fascia is a suitable target for cervical plexus blocks. This injection site describes an intermediate cervical plexus block. As the compartment contains the sensory terminal branches of the spinal nerves C2-4, it may be referred to as C2-C4 compartment. The cranio-caudal spread of the injectate allows lateromedial needle guidance in the horizontal plane. As the superficial lamina is not a barrier to the injectate an additional subcutaneous infiltration of the nerve area appears dispensable. The prevertebral lamina proved to be impermeable to injected methylene blue. Whether phrenic nerve blocks are preventable with more distal intermediate cervical plexus blocks (selective block of the supraclavicular nerves, e.g. for surgery of the clavicle) must be investigated in clinical trials. The permanent anastomosis (superficial cervical ansa) between the cervical plexus and the ramus colli of the facial nerve provides an anatomically reasonable explanation for inadequate cervical plexus blocks.

Adaptation of the chronic disease self-management program for cancer survivors: feasibility, acceptability, and lessons for implementation.

Self-management in chronic disease has been shown to improve patient-reported and health care-related outcomes. However, relatively little information about its utility in cancer survivorship is known. We evaluated the feasibility and acceptability of the delivery of an adaptation of the evidence-based Chronic Disease Self-management Program (Stanford) called Cancer Thriving and Surviving (CTS). Triangulated mixed methods were used to capture baseline characteristics and post-program experiences using a combination of closed- and open-ended survey items; emergent coding and simple descriptive statistics were used to summarize the data. Twenty-seven workshops were delivered by 22 CTS leaders to 244 participants between August 2011 and January 2013 in a variety of settings (48 % community, 30 % health care, 22 % regional/community cancer center). Representing a variety of cancer types, about half the participants were 1-3 years post-diagnosis and 45 % were 4 or more years from diagnosis. Program attendance was high with 84 % of participants attending four or more of the six sessions in the workshop. Overall, 95 % of the participants were satisfied with the program content and leaders, and would recommend the program to friends and family. These results confirm the feasibility and acceptability of delivery of a high-fidelity, peer-led model for self-management support for cancer survivors. Expansion of the CTS represents a powerful tool toward improving health-related outcomes in this at-risk population.

[Werner Leibbrand as psychiatric opponent of National Socialism]. / Werner Leibbrand als psychiatrischer Gegner des Nationalsozialismus.

The psychiatrist and medical historian Werner Leibbrand resigned from the Berlin Medical Association after the seizure of power in protest against the exclusion of Jewish colleagues and lost both the license to practice as well as his professional position in the public health service. After the end of the war the American military authorities appointed him as expert witness for the prosecution in the Nürnberg Doctors Trial. In addition to a biographical review, Leibbrand's resolute although still undisputed attitude as ethical expert in the trials will be roughly outlined.

Structure-function relationship of the foam-like pomelo peel (Citrus maxima)-an inspiration for the development of biomimetic damping materials with high energy dissipation.

The mechanical properties of artificial foams are mainly determined by the choice of bulk materials and relative density. In natural foams, in contrast, variation to optimize properties is achieved by structural optimization rather than by conscious substitution of bulk materials. Pomelos (Citrus maxima) have a thick foam-like peel which is capable of dissipating considerable amounts of kinetic energy and thus this fruit represents an ideal role model for the development of biomimetic impact damping structures. This paper focuses on the analysis of the biomechanics of the pomelo peel and on its structure-function relationship. It deals with the determination of the onset strain of densification of this foam-like tissue and on how this property is influenced by the arrangement of vascular bundles. It was found here that the vascular bundles branch in a very regular manner-every 16.5% of the radial peel thickness-and that the surrounding peel tissue (pericarp) attains its exceptional thickness mainly by the expansion of existing interconnected cells causing an increasing volume of the intercellular space, rather than by cell division. These findings lead to the discussion of the pomelo peel as an inspiration for fibre-reinforced cast metallic foams with the capacity for excellent energy dissipation.

[Distal sciatic nerve blocks: randomized comparison of nerve stimulation and ultrasound guided intraepineural block]. / Distale Blockaden des N. ischiadicus : Randomisierter Vergleich zwischen Nervenstimulation und ultraschallgestützter intraepineuraler Blockade.

BACKGROUND AND OBJECTIVES: The design of this study is related to an important current issue: should local anesthetics be intentionally injected into peripheral nerves? Answering this question is not possible without better knowledge regarding classical methods of nerve localization (e.g. cause of paresthesias and nerve stimulation technique). Have intraneural injections ever been avoided? This prospective, randomized comparison of distal sciatic nerve block with ultrasound guidance tested the hypothesis that intraneural injection of local anesthetics using the nerve stimulation technique is common and associated with a higher success rate. MATERIAL AND METHODS: In this study 250 adult patients were randomly allocated either to the nerve stimulation group (group NS, n = 125) or to the ultrasound guidance group (group US, n = 125). The sciatic nerve was anesthetized with 20 ml prilocaine 1% and 10 ml ropivacaine 0.75%. In the US group the goal was an intraepineural needle position. In the NS group progress of the block was observed by a second physician using ultrasound imaging but blinded for the investigator performing the nerve stimulation. The main outcome variables were time until readiness for surgery (performance time and onset time), success rate and frequency of paresthesias. In the NS group needle positions and corresponding stimulation thresholds were recorded. RESULTS: In both groups seven patients were excluded from further analysis because of protocol violation. In the NS group (n = 118) the following needle positions were estimated: intraepineural (NS 1, n = 51), extraparaneural (NS 2, n = 33), needle tip dislocation from intraepineural to extraparaneural while injecting local anesthetic (NS 3, n = 19) and other or not determined needle positions (n = 15). Paresthesias indicated an intraneural needle position with an odds ratio of 27.4 (specificity 98.8%, sensitivity 45.9%). The success rate without supplementation was significantly higher in the US group (94.9% vs. 61.9%, p < 0.001) and the time until readiness for surgery was significantly (p < 0.001) shorter for successful blocks: 15.1 min (95% confidence interval CI 13.6-16.5 min) vs. 28 min (95% CI 24.9-31.1 min). In the NS subgroups the results were as follows (95% CI in brackets): NS1 88.2% and 22.7 min (19.5-25.9 min), NS2 24.2% and 43.3 min (35.5-51.1 min) and NS3 36.8% and 35.3 min (22.1-48.4 min). CONCLUSIONS: For distal sciatic nerve blocks using the nerve stimulation technique, intraepineural injection of local anesthetics is common and associated with significant and clinically important higher success rates as well as shorter times until readiness for surgery. In both groups no block-related nerve damage was observed. The results indicate that for some blocks (e.g. sciatic, supraclavicular) perforation of the outer layers of connective tissue was always an important prerequisite for success using classical methods of nerve localization (cause of paresthesias and nerve stimulation technique). Additional nerve stimulation with an ultrasound-guided distal sciatic nerve block cannot make any additional contribution to the safety or success of the block. New insights concerning the architecture of the sciatic nerve are discussed and associated implications for the performance of distal ultrasound-guided sciatic nerve block are addressed.

[Successful use of C1 esterase inhibitor in capillary leak syndrome]. / Erfolgreiche Anwendung von C1-Esterase-Inhibitor bei "capillary leak syndrome"

This article reports the successful use of C1 esterase inhibitor in the treatment of capillary leak syndrome. The coincidence of exposure to latex during surgery and medication with ramipril led to prolonged shock complicated by secondary hyperfibrinolysis, capillary leak syndrome and multiple organ failure. Initial treatment according to relevant guidelines failed to stabilize the condition. Treatment was only successful after administration of 1,500 IU of human C1 esterase inhibitor.

1,10-Phenanthrolinium hydrogensquarate monohydrate--a non-centrosymmetric structure from two non-chiral agents.

The novel hydrogensquarate salt of 1,10-phenanthroline has been synthesized, isolated and structurally elucidated by single crystal X-ray diffraction. 1,10-Phenanthrolinium hydrogensquarate monohydrate (1) crystallizes in the non-centrosymmetric P2(1) space group. Its hydrogensquarate anions form a stable dimer by means of ((Sq))OHc...O=C((Sq)) hydrogen bonds with lengths of 2.509, 2.526, 2.510, and 2.524A. The solvent water molecule interacts with the anion dimers by means of strong and moderate hydrogen bonds HOHc...O=C((Sq)) with bond lengths of 2.782 and 2.845A, respectively. The 1,10-phenanthrolinium cation participates in NHc...OH(2) interactions with the water molecule (bond lengths of 2.810, 2.758, 2.779 and 2.760A). Surprisingly, compound contains four independent molecules in the unit cell. Optical properties were elucidated by means of linear-polarized solid-state IR-spectroscopy and UV-spectroscopy. In addition TGA, DSC, DTA data, positive and negative ESI mass spectra as well as (1)H- and (13)C NMR spectra are presented. Quantum chemical methods were used to calculate the electronic structure, vibrational data and electronic spectra as well as non-linear optical properties of neutral 1,10-phenanthroline and its protonated cation. Second harmonic generation measurements of the novel compound demonstrate that the compound possesses effective d coefficients of 1.9+/-0.5 pm V(-1), value that is about three times higher that of the low temperature form of potassium dideuterophosphate.

Biaxial cell stimulation: A mechanical validation.

To analyse mechanotransduction resulting from tensile loading under defined conditions, various devices for in vitro cell stimulation have been developed. This work aimed to determine the strain distribution on the membrane of a commercially available device and its consistency with rising cycle numbers, as well as the amount of strain transferred to adherent cells. The strains and their behaviour within the stimulation device were determined using digital image correlation (DIC). The strain transferred to cells was measured on eGFP-transfected bone marrow-derived cells imaged with a fluorescence microscope. The analysis was performed by determining the coordinates of prominent positions on the cells, calculating vectors between the coordinates and their length changes with increasing applied tensile strain. The stimulation device was found to apply homogeneous (mean of standard deviations approx. 2% of mean strain) and reproducible strains in the central well area. However, on average, only half of the applied strain was transferred to the bone marrow-derived cells. Furthermore, the strain measured within the device increased significantly with an increasing number of cycles while the membrane's Young's modulus decreased, indicating permanent changes in the material during extended use. Thus, strain magnitudes do not match the system readout and results require careful interpretation, especially at high cycle numbers.