Numerical evaluation of internal femur osteosynthesis based on a biomechanical model of the loading in the proximal equine hindlimb.

Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a "gap" fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types.

Individualized Training of Back Muscles Using Iterative Learning Control of a Compliant Balance Board.

Here we present the GyroTrainer, a bespoke mechatronic balance board system designed to trigger activation of the back muscles while the user engages in a balance-challenging game. The GyroTrainer uses admittance control coupled with an iterative learning approach so as to tailor the admittance control parameters, i.e. difficulty level, according to the user's skill. Our experimental evaluation demonstrated that an individualized admittance control stiffness could be identified for each user, which corresponds with a desired level of difficulty and increased back muscle activity. A first game implementation demonstrates the feasibility of utilizing the GyroTrainer system and the individually identified admittance control stiffness for gamification of back muscle training.

Direct Cyclopalladation of Fluorinated Benzyl Amines by Pd3(OAc)6: The Coexistence of Multinuclear Pdn Reaction Pathways Highlights the Importance of Pd Speciation in C-H Bond Activation.

Palladacycles are key intermediates in catalytic C-H bond functionalization reactions and important precatalysts for cross-couplings. It is commonly believed that palladacycle formation occurs through the reaction of a substrate bearing a C-H bond ortho to a suitable metal-directing group for interaction with, typically, mononuclear "Pd(OAc)2" species, with cyclopalladation liberating acetic acid as the side product. In this study, we show that N,N-dimethyl-fluoro-benzyl amines, which can be cyclopalladated either ortho or para to fluorine affording two regioisomeric products, can occur by a direct reaction of Pd3(OAc)6, proceeding via higher-order cyclopalladated intermediates. Regioselectivity is altered subtly depending on the ratio of substrate:Pd3(OAc)6 and the solvent used. Our findings are important when considering mechanisms of Pd-mediated reactions involving the intermediacy of palladacycles, of particular relevance in catalytic C-H bond functionalization chemistry.

The minimum required overlap length for tendon transfer A biomechanical study on human tendons.

In tendon transfer surgeries sufficient stability of the tenorrhaphy is essential. In addition to the choice of a suitable technique, adequate overlap of donor and recipient tendons must be ensured. The aim of this study was to investigate the tensile strength with regard to tendon overlap of a recently published tenorrhaphy, termed Woven-Fridén (WF) tenorrhaphy, which displayed higher tensile strength and lower bulk when compared to the established Pulvertaft technique. For this purpose, WF tenorrhaphies with 1.5 cm, 2 cm, and 3 cm tendon overlap were performed and subsequently tested for different biomechanical properties by tensile testing. Among others, the parameters of ultimate load and stiffness were collected. Native tendons served as controls. A formula was derived to quantify the relation between tendon overlap and ultimate load. We observed that sufficient tensile strength (mean ultimate load of 217 N) is already given with a 2 cm tendon overlap. In addition, with more than 3 cm overlap length only little additional tensile strength is to be expected as the calculated ultimate load of 4 cm overlap (397 N) is approaching the plateau of the maximal ultimate load of 435 N (native tendons).

Enantiodiscrimination of Inherently Chiral Thiacalixarenes by Residual Dipolar Couplings.

Inherently chiral compounds, such as calixarenes, are chiral due to a nonplanar three-dimensional (3D) structure. Determining their conformation is essential to understand their properties, with nuclear magnetic resonance (NMR) spectroscopy being one applicable method. Using alignment media to measure residual dipolar couplings (RDCs) to obtain structural information is advantageous when classical NMR parameters like the nuclear Overhauser effect (NOE) or J-couplings fail. Besides providing more accurate structural information, the alignment media can induce different orientations of enantiomers. In this study, we examined the ability of polyglutamates with different side-chain moieties─poly-γ-benzyl-l-glutamate (PBLG) and poly-γ-p-biphenylmethyl-l-glutamate (PBPMLG) ─to enantiodifferentiate the inherently chiral phenoxathiin-based thiacalix[4]arenes. Both media, in combination with two solvents, allowed for enantiodiscrimination, which was, to the best of our knowledge, proved for the first time on inherently chiral compounds. Moreover, using the experimental RDCs, we investigated the calix[4]arenes conformational preferences in solution, quantitatively analyzed the differences in the alignment of the enantiomers, and discussed the pitfalls of the use of the RDC analysis.

Development of an Exoskeleton Platform of the Finger for Objective Patient Monitoring in Rehabilitation.

This paper presents the application of an adaptive exoskeleton for finger rehabilitation. The system consists of a force-controlled exoskeleton of the finger and wireless coupling to a mobile application for the rehabilitation of complex regional pain syndrome (CRPS) patients. The exoskeleton has sensors for motion detection and force control as well as a wireless communication module. The proposed mobile application allows to interactively control the exoskeleton, store collected patient-specific data, and motivate the patient for therapy by means of gamification. The exoskeleton was applied to three CRPS patients over a period of six weeks. We present the design of the exoskeleton, the mobile application with its game content, and the results of the performed preliminary patient study. The exoskeleton system showed good applicability; recorded data can be used for objective therapy evaluation.

Pulsatile Lavage During Cementation of Total Knee Arthroplasty - Is Fixation Impaired? A Cadaver Study.

BACKGROUND/AIM: Increasing economic pressure in modern healthcare necessitates an increase in efficiency in total knee arthroplasty (TKA) while maintaining high-quality outcomes. Removal of debris using pulsatile lavage (PL) during cement polymerization may considerably reduce the operative duration. However, water can penetrate the interface, resulting in impaired implant fixation. The aim of the present study was to investigate the impact of early-onset PL during bone cement polymerization on implant fixation and operative duration. MATERIALS AND METHODS: Cemented implantation of tibial trays was performed in 20 fresh-frozen human tibiae from 10 donors in a matched-pair study design in two groups: 1) PL during cement polymerization; and 2) PL after completion of the polymerization process. The cement penetration depth was analysed by computed tomography (CT), and the pull-out force was measured to evaluate primary implant fixation. The duration of the procedure was recorded for both groups. RESULTS: Comparable pull-out forces were observed in the experimental (2,213 N) and control groups (2,350 N; p=0.68). The mean depth of cement penetration was similar in both groups. PL during cement polymerization could decrease the operative duration by 10 min. CONCLUSION: The application of PL during cement polymerization could significantly reduce operative duration and had no adverse effect on the mechanical fixation of the tibial component.

Fine tuning of the side-to-side tenorrhaphy: A biomechanical study assessing different side-to-side suture techniques in a porcine tendon model.

Recent studies conclude that a new technique for tendon transfers, the side-to-side tenorrhaphy by Fridén (FR) provides higher biomechanical stability than the established standard first described by Pulvertaft (PT). The aim of this study was to optimize side-to-side tenorrhaphies. We compared PT and FR tenorrhaphies as well as a potential improvement, termed Woven-Fridén tenorrhaphy (WF), with regard to biomechanical stability. Our results demonstrate superior biomechanical stability and lower bulk of FR and, in particular, WF over PT tenorrhaphies. The WF and FR technnique therefore seem to be a notable alternative to the established standard tenorrhaphy as they display lower bulk and higher stability, permitting successful immediate active mobilization after surgery.

Improving mandibular reconstruction by using topology optimization, patient specific design and additive manufacturing?-A biomechanical comparison against miniplates on human specimen.

In this study, topology optimized, patient specific osteosynthesis plates (TOPOS-implants) are evaluated for the mandibular reconstruction using fibula segments. These shape optimized implants are compared to a standard treatment with miniplates (thickness: 1.0 mm, titanium grade 4) in biomechanical testing using human cadaveric specimen. Mandible and fibula of 21 body donors were used. Geometrical models were created based on automated segmentation of CT-scans of all specimens. All reconstructions, including cutting guides for osteotomy as well as TOPOS-implants, were planned using a custom-made software tool. The TOPOS-implants were produced by electron beam melting (thickness: 1.0 mm, titanium grade 5). The fibula-reconstructed mandibles were tested in static and dynamic testing in a multi-axial test system, which can adapt to the donor anatomy and apply side-specific loads. Static testing was used to confirm mechanical similarity between the reconstruction groups. Force-controlled dynamic testing was performed with a sinusoidal loading between 60 and 240 N (reconstructed side: 30% reduction to consider resected muscles) at 5 Hz for up to 5 · 105 cycles. There was a significant difference between the groups for dynamic testing: All TOPOS-implants stayed intact during all cycles, while miniplate failure occurred after 26.4% of the planned loading (1.32 · 105 ± 1.46 · 105 cycles). Bone fracture occurred in both groups (miniplates: n = 3, TOPOS-implants: n = 2). A correlation between bone failure and cortical bone thickness in mandible angle as well as the number of bicortical screws used was demonstrated. For both groups no screw failure was detected. In conclusion, the topology optimized, patient specific implants showed superior fatigue properties compared to miniplates in mandibular reconstruction. Additionally, the patient specific shape comes with intrinsic guiding properties to support the reconstruction process during surgery. This demonstrates that the combination of additive manufacturing and topology optimization can be beneficial for future maxillofacial surgery.

Suspension button constructs restore posterior knee laxity in solid tibial avulsion of the posterior cruciate ligament.

PURPOSE: Dislocated tibial avulsions of the posterior cruciate ligament (PCL) require surgical intervention. Several arthroscopic strategies are options to fix the fragment and restore posterior laxity, including two types of suspension button devices: adjustable (self-locking) and rigid knotted systems. Our hypothesis was that a rigid knotted button construct has superior biomechanical properties regarding laxity restoration compared with an adjustable system. Both techniques were compared with standard screw fixation and the native PCL. METHODS: Sixty porcine knees were dissected. The constructs were tested for elongation, stiffness, yield force, load to failure force, and failure mode in a material testing machine. Group N (native, intact PCL) was used as a control group. In group DB (Dogbone™), TR (Tightrope™), and S (screw), a standardized block osteotomy with the osteotomized fragment attached to the PCL was set. The DB and TR groups simulated using a suspension button system with either a rigid knotted (DB) or adjustable system (TR). These groups were compared to a screw technique (S) simulating antegrade screw fixation from posterior. RESULTS: Comparing the different techniques (DB, TR, S), no significant elongation was detected; all techniques achieved a sufficient posterior laxity restoration. Significant elongation in the DB and TR group was detected compared with the native PCL (N). In contrast, screw fixation did not lead to significant elongation. The stiffness, yield load, and load to failure force did not differ significantly between the techniques. None of the techniques reached the same level of yield load and load to failure force as the intact state. CONCLUSION: Arthroscopic suspension button techniques sufficiently restore the posterior laxity and gain a comparable construct strength as an open antegrade screw fixation.

Exploring the potential of PCA-based quantitation of NMR signals in T1 relaxometry.

Principal component analysis (PCA) has proved to be a powerful technique for processing NMR data. It is particularly useful in signal quantitation where it often provides better results compared to a direct integration of individual signals. In the present work, we recapitulate the principles and theoretical framework underlying PCA-based quantitation with a special focus on T1 relaxometry. We show that under commonly encountered conditions, this approach can provide up to ~4-fold improvement in scatter of points in magnetization build-up curves compared to direct integration. Best practices to optimize the PCA performance in measuring the total magnetization are discussed, including minimization of the number of signal-related principal components and a proper selection of FT parameters and data quantitation intervals. For signals consisting of distinct relaxation components, formulas are provided for resolving the components relaxation and illustrated on a real-data example. In addition to the problem of quantitation, the use of PCA in denoising of partially relaxed spectra is discussed in connection with such applications as line shape analysis and monitoring relaxation of individual spectral components.

Modified suture-bridge technique for tibial avulsion fractures of the posterior cruciate ligament: a biomechanical comparison.

PURPOSE: Displaced tibial posterior cruciate ligament (PCL) avulsion fractures require surgical fixation in order to provide an adequate bone healing and to avoid a loss of posterior stability. The purpose of this study was to compare the biomechanical properties of a recently established modified suture bridge technique to a well-established transtibial pullout technique. It was hypothesized that the suture bridge technique shows lower elongation and higher load to failure force compared to a transtibial pullout fixation. METHODS: Twelve fresh-frozen human cadaveric knees were biomechanically tested using an uniaxial hydrodynamic material testing system. A standardized bony avulsion fracture of the tibial PCL insertion was generated. Two different techniques were used for fixation: (A) suture bridge configuration and (B) transtibial pullout fixation. In 90° of flexion elongation, initial stiffness and failure load were determined. RESULTS: The suture-bridge technique resulted in a significant lower elongation (4.5 ± 2.1 mm) than transtibial pullout technique (12.4 ± 3.0 mm, p < 0.001). The initial stiffness at the beginning of cyclic loading was 46.9 ± 3.9 N/mm in group A und 40.8 ± 9.0 N/mm in group B (p = 0.194). Load to failure testing exhibited 286.8 ± 88.3 N in group A and 234.3 ± 96.8 N in group B (p = 0.377). CONCLUSION: The suture bridge technique provides a significant lower construct elongation during cyclic loading. But postoperative rehabilitation must respect the low construct strength of both techniques because both fixation techniques did not show a sufficient fixation strength to allow for a more aggressive rehabilitation.

Varus alignment aggravates tibiofemoral contact pressure rise after sequential medial meniscus resection.

PURPOSE: Arthroscopic partial meniscectomy of medial meniscus tears and varus alignment are considered independent risk factors for increased medial compartment load, thus contributing to the development of medial osteoarthritis. The purpose of this biomechanical study was to investigate the effect of lower limb alignment on contact pressure and contact area in the knee joint following sequential medial meniscus resection. It was hypothesized that a meniscal resection of 50% would lead to a significant overload of the medial compartment in varus alignment. METHODS: Eight fresh-frozen human cadaveric knees were axially loaded with a 750 N compressive force in full extension with the mechanical axis rotated to intersect the tibia plateau at 30%, 40%, 50%, 60% and 70% of its width. Tibiofemoral mean contact pressure (MCP), peak contact pressure (PCP), and contact area (CA) of the medial and lateral compartment were measured separately using pressure-sensitive films (K-Scan 4000, Tekscan) in four different meniscal conditions, respectively, intact, 50% resection, 75% resection, and total meniscectomy. RESULTS: Medial MCP was significantly increased when comparing the intact meniscus to each meniscal resection in all tested alignments (p < 0.05). Following meniscal resection of 50%, MCP was significantly higher with greater varus alignment compared to valgus alignment (p < 0.05). Similarly, medial PCP was higher at varus alignment compared to valgus alignment (p < 0.05). Further resection to 75% and 100% of the meniscus resulted in a significantly higher medial PCP at 30% of tibia plateau width compared to all other alignments (p < 0.05). Medial CA of the intact meniscus decreased significantly after 50%, 75% and 100% meniscal resection in all alignments (p < 0.05). Lateral joint pressure was not significantly increased by greater valgus alignment. CONCLUSION: Lower limb alignment and the extent of medial meniscal resection significantly affect tibiofemoral contact pressure. Combined varus alignment and medial meniscal resection increased MCP and PCP within the medial compartment, whereas valgus alignment prevented medial overload. As a clinical consequence, lower limb alignment should be considered in the treatment of patients undergoing arthroscopic partial meniscectomy with concomitant varus alignment. In patients presenting with ongoing medial joint tenderness and effusion, realignment osteotomy can be a surgical technique to unload the medial compartment.

Varus alignment increases medial meniscus extrusion and peak contact pressure: a biomechanical study.

PURPOSE: Assessment of medial meniscus extrusion (MME) has become increasingly popular in clinical practice to evaluate the dynamic meniscus function and diagnose meniscus pathologies. The purpose of this biomechanical study was to investigate the correlation between MME and the changes in joint contact pressure in varus and valgus alignment. It was hypothesized that varus alignment would result in significantly higher MME along with a higher joint contact pressure in the medial compartment. METHODS: Eight fresh-frozen human cadaveric knees were axially loaded, with a 750 N compressive load, in full extension with the mechanical axis shifted to intersect the tibial plateau at 30% and 40% (varus), 50% (neutral), 60% and 70% (valgus) of its width (TPW). Tibiofemoral peak contact pressure (PCP), mean contact pressure (MCP) and contact area (CA) were determined using pressure-sensitive films. MME was obtained via ultrasound at maximum load. RESULTS: MME was significantly increased from valgus (1.32 ± 0.22 mm) to varus alignment (3.16 ± 0.24 mm; p < 0.001). Peak contact pressure at 30% TPW varus alignment was significantly higher compared to 60% TPW valgus (p = 0.018) and 70% TPW valgus (p < 0.01). MME significantly correlated with PCP (r = 0.56; p < 0.001) and MCP (r = 0.47, p < 0.01) but not with CA (r = 0.23; n.s.). CONCLUSION: MME was significantly increased in varus alignment, compared to neutral or valgus alignment, with an intact medial meniscus. It was also significantly correlated with PCP and MCP within the medial compartment. However, valgus malalignment and neutral axis resulted in reduced MME and contact pressure. Lower limb alignment must be taken into account while assessing MME in clinical practice. LEVEL OF EVIDENCE: Controlled laboratory study.

Nuclear magnetic resonance investigation of water transport through the plasma membrane of various yeast species.

A specific technique of nuclear magnetic resonance (NMR) spectroscopy, filter-exchange spectroscopy (FEXSY), was employed to investigate water transport through the plasma membrane in intact yeast cells. This technique allows water transport to be monitored directly, thus avoiding the necessity to subject the cells to any rapid change in the external conditions, e.g. osmotic shock. We established a sample preparation protocol, a data analysis procedure and verified the applicability of FEXSY experiments. We recorded the exchange rates in the temperature range 10-40°C for Saccharomyces cerevisiae. The resulting activation energy of 29 kJ mol-1 supports the hypothesis that water exchange is facilitated by water channels-aquaporins. Furthermore, we measured for the first time water exchange rates in three other phylogenetically unrelated yeast species (Schizosaccharomyces pombe, Candida albicans and Zygosaccharomyces rouxii) and observed remarkably different water exchange rates between these species. Findings of our work contribute to a better understanding of as fundamental a cell process as the control of water transport through the plasma membrane.

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling.

The synthesis of the polyketide section present in the potently cytotoxic marine cyclodepsipeptide jasplakinolide and related natural products, geodiamolides and seragamides, is reported. The key step is a Negishi cross coupling of (R)-(3-methoxy-2-methyl-3-oxopropyl)zinc(II) bromide and an (E)-iodoalkene that was synthesized via an aluminium ester enolate attack at (R)-propylene oxide. The overall synthesis comprises nine steps with an overall yield of 21%. It proved to be possible to liberate the free 8-hydroxynonenoic acid and to couple it with a protected tripeptide composed of L-alanine, N,O-dimethyl-D-iodotyrosine, and TIPS-protected L-threonine, which occurs as partial structure of seragamide A. The tripeptide section of seragamide A was assembled by solution-phase synthesis and an open-chain analogue of the natural product was obtained.

Structural Modulation of Chromic Response: Effects of Binding-Site Blocking in a Conjugated Calix[4]pyrrole Chromophore.

Herein, we modulate the chromic response of a highly colored tetrapyrrole macrocycle, namely, tetrakis(3,5-di-tert-butyl-4-oxocyclohexadien-2,5-yl)porphyrinogen (OxP) by structural modification. N-Benzylation at the macrocyclic nitrogen atoms leads to stepwise elimination of the two calix[4]pyrrole-type binding sites of OxP and serial variation of the chromic properties of the products, double N-benzylated Bz2OxP and tetra N-benzylated Bz4OxP. The halochromic (response to acidity) and solvatochromic (response to solvent polarity) properties were studied by using UV/Vis spectroscopy and NMR spectroscopy in nonpolar organic solvents. Titration experiments were used to generate binding isotherms to elucidate their binding properties with difluoroacetic acid. Differences in the halochromic properties of the compounds allowed construction of a colorimetric scale of acidity in nonpolar solvents, as the compounds in the series OxP, Bz2OxP, and Bz4OxP are increasingly difficult to protonate but maintain their propensity to change color upon protonation. The concurrent effects of binding-site blocking and modulation of acidity sensitivity are important new aspects for the development of colorimetric indicators.

The role of trinuclear species in a palladium acetate/trifluoroacetic acid catalytic system.

Reactions catalyzed by palladium(ii) acetate and trifluoroacetic acid (TFA) have a clear preactivation phase. However, the structure of real catalytic species remains unclear. We show that the key species are cyclic trinuclear complexes of composition [Pd3(OAc)6-x(OTFA)x] (x = 1-6) formed by a sequential ligand exchange from [Pd3(OAc)6]. Furthermore, we prove that the trinuclear palladium backbone of the precatalyst remains preserved during the first phase of the C-H activation reaction of acetanilides. In other words, the reaction pathway including the trinuclear species should be taken into account in discussion about mechanisms of the reactions catalyzed by palladium acetates.

Paramagnetic 19F Relaxation Enhancement in Nickel(II) Complexes of N-Trifluoroethyl Cyclam Derivatives and Cell Labeling for 19F MRI.

1,8-Bis(2,2,2-trifluoroethyl)cyclam (te2f) derivatives with two coordinating pendant arms involving methylenecarboxylic acid (H2te2f2a), methylenephosphonic acid (H4te2f2p), (2-pyridyl)methyl (te2f2py), and 2-aminoethyl arms (te2f2ae) in 4,11-positions were prepared, and their nickel(II) complexes were investigated as possible 19F MR tracers. The solid-state structures of several synthetic intermediates, ligands, and all complexes were confirmed by X-ray diffraction analysis. The average Ni···F distances were determined to be about 5.2 Å. All complexes exhibit a trans-III cyclam conformation with pendant arms bound in the apical positions. Kinetic inertness of the complexes is increased in the ligand order te2f2ae ≪ te2f < te2f2py ≈ H4te2f2p ≪ H2te2f2a. The [Ni(te2f2a)] complex is the most kinetically inert Ni(II) complex reported so far. Paramagnetic divalent nickel caused a shortening of 19F NMR relaxation time down to the millisecond range. Solubility, stability, and cell toxicity were only satisfactory for the [Ni(te2f2p)]2- complex. This complex was visualized by 19F MRI utilizing an ultrashort echo time (UTE) imaging pulse sequence, which led to an increase in sensitivity gain. Mesenchymal stem cells were successfully loaded with the complex (up to 0.925/5.55 pg Ni/F per cell).19F MRI using a UTE pulse sequence provided images with a good signal-to-noise ratio within the measurement time, as short as tens of minutes. The data thus proved a major sensitivity gain in 19F MRI achieved by utilization of the paramagnetic (transition) metal complex as 19F MR tracers coupled with the optimal fast imaging protocol.

Total Synthesis of the Marine Natural Product Hemiasterlin by Organocatalyzed α-Hydrazination.

An efficient synthesis of the potently cytotoxic marine peptide hemiasterlin is presented. The tetramethyltryptophan moiety is assembled by tert-prenylation of indole, followed by the high-yielding organocatalyzed α-hydrazination of a sterically congested aldehyde with excellent enantioselectivity. 2-Bromo-N-ethylpyridinium tetrafluoroborate (BEP)-mediated peptide coupling completes the synthesis, being the first approach that does not employ chiral auxiliaries. A novel phenonium-type rearrangement of the indole system occurred when subjecting dihydroxylated 3-tert-prenylindole to Mitsunobu conditions.