Systematic review: isocaloric ketogenic dietary regimes for cancer patients.

The efficacy and benefits of ketogenic diets (KD) have recently been gaining worldwide and remain a controversial topic in oncology. This systematic review therefore presents and evaluates the clinical evidence on isocaloric KD dietary regimes and reveals that evidence supporting the effects of isocaloric ketogenic dietary regimes on tumor development and progression as well as reduction in side effects of cancer therapy is missing. Furthermore, an array of potential side effects should be carefully considered before applying KD to cancer patients. In regard to counseling cancer patients considering a KD, more robust and consistent clinical evidence is necessary before the KD can be recommended for any single cancer diagnosis or as an adjunct therapy.

Platelets from flowing blood attach to the inflammatory chemokine CXCL16 expressed in the endothelium of the human vessel wall.

Endothelial chemokine CXC motif ligand 16 (CXCL16) expression is associated with atherosclerosis, while platelets, particularly those attaching to atherosclerotic plaque, contribute to all stages of atherosclerotic disease. This investigation was designed to examine the role of CXCL16 in capturing platelets from flowing blood. CXCL16 was expressed in human atherosclerotic plaques, and lesion severity in human carotid endarterectomy specimens was positively correlated with CXCL16 levels. CXCL16 expression in plaques was co-localised with platelets deposited to the endothelium. Immobilised CXCL16 promoted CXCR6-dependent platelet adhesion to the human vessel wall, endothelial cells and von Willebrand factor during physiologic flow. At low shear, immobilised CXCL16 captured platelets from flowing blood. It also induced irreversible platelet aggregation and a rise in intra-platelet calcium levels. These results demonstrate that endothelial CXCL16's action on platelets is not only limited to platelet activation, but that immobilised CXCL16 also acts as a potent novel platelet adhesion ligand, inducing platelet adhesion to the human vessel wall.

Immunological detection of osteocalcin in meat and bone meal: a novel heat stable marker for the investigation of illegal feed adulteration.

A sandwich ELISA was developed for the detection of bovine meat and bone meal (BMBM) in feed, based on polyclonal rabbit antibodies raised against the synthetic N-terminal amino acid sequence 1-9 (YLDHWLGAP) of bovine osteocalcin. To set up a sandwich ELISA pair, a commercial mouse monoclonal capture antibody binding to a highly conserved epitope in the mid-fragment of the peptide was employed. It is shown that the bone marker osteocalcin is immunologically well detectable in BMBM extracts obtained by a simple EDTA-based procedure even in a sample heated up to 145°C. Furthermore, a genus-specific restriction of the major specificity to cattle and horse was possible. The observed bi-specificity is consistent with theoretical predictions. The assay sensitivity with bovine osteocalcin of 1 ng was sufficient to enable the detection of 0.1% BMBM in compound plant feed or fish meal, for which no cross reaction was observed. In general the quantification of osteocalcin in extracts is possible using a standard curve procedure with pure bovine osteocalcin.

Bioenergy from permanent grassland--a review: 1. Biogas.

Grassland biomass is suitable in numerous ways for producing energy. It is well established as feedstock for biogas production. The aim of this review is to summarize current knowledge on suitability and sustainability of grassland biomass for anaerobic digestion. In the first section grassland management for biogas feedstock as well as specifics of harvest, postharvest and digestion technology are described. Methane yields from grass are influenced by many factors. While the effects of some parameters such as grass species, cutting period and management intensity can be regarded as well known, other parameters such as preservation and processing still need investigation. In the second section economic aspects and environmental impacts are discussed. Profitability can be achieved depending on grass silage supply costs and the concept of anaerobic digestion and energy use. Grassland biomass for biogas production competes with other feedstock and other forms of grassland use, in particular animal husbandry. In developed countries a growing production of milk and meat is achieved with decreasing ruminant numbers, resulting in an increasing amount of surplus grassland with a remarkable bioenergy potential. In emerging and developing countries a rapidly rising demand for and production of milk and meat induce growing pressure on grasslands, so that their use for animal feed presumably will take priority over use for bioenergy. Grasslands provide a variety of essential environmental benefits such as carbon storage, habitat function, preservation of ground and surface water quality. When producing biogas from grassland these benefits will remain or even grow, providing appropriate grassland management is implemented. In particular, greenhouse gas emissions can be considerably reduced.

Angle stable interlocking screws improve construct stability of intramedullary nailing of distal tibia fractures: a biomechanical study.

INTRODUCTION: Intramedullary nailing is the treatment of choice for most displaced tibial shaft fractures. The ability to maintain a mechanically stable fixation becomes more difficult the further the fracture extends distally or proximally or when unreamed tibial nails are used. We assumed that a new angular stable locking option would provide improved stability and reduced interfragmentary movements in a distal tibia in vitro fracture model. MATERIALS AND METHODS: Left and right bones of 8 pairs of human cadaveric tibiae were randomly assigned to either a group with conventional locked or a group with angular stable locked intramedullary nails. Nails of 10-mm-diameter were used after reaming up to 11 mm. A transverse distal osteotomy was performed and the specimens were tested mechanically under eccentric axial load. A video optical measurement system was used to determine the angular displacement of the osteotomy gap during loading. RESULTS: Construct stiffness, maximum load of the bone-nail construct and gap angle at 0.5 kN load were measured. The group with the angular stable locking option showed significantly higher stiffness values and reduced fracture gap motion compared to the group with conventional locked nails. DISCUSSION: A new angular stable locking option of intramedullary nails provides higher stability in terms of construct stiffness and reduced interfragmentary movements in a distal tibia in vitro fracture model.

Kinetic study of biogas production from energy crops and animal waste slurry: effect of organic loading rate and reactor size.

Biogas production in agriculture is processed mostly continuously at mesophilic temperatures in completely stirred tank reactors. Therefore, reactor performance data were studied in long-term semi-continuous laboratory-scale experiments with maize silage, whole-crop rye silage and fodder beet silage as mono-substrate and cattle slurry at mesophilic temperatures. For calculation of biogas yield as function of the organic loading rate, a hyperbolic equation was developed on the base of a first-order reaction rate for substrate degradation. The biogas yield depends also on the maximum biogas yield, the concentration of volatile solids of the input, the density of the effluent, the density of the biogas and the reaction rate constant, which are all substrate- or process-specific. Values of the theoretical maximum biogas yield and the reaction rate constant were observed in the range 0.61-0.93 m3 per kg volatile solids and 0.032-0.316 d(-1), respectively. By means of the hyperbolic equation, the proportion of the biogas yield from the maximum can be calculated for the first and a second reactor which also depends on the volume of each reactor.

Mechanical properties of 18 different AO bone plates and the clamp-rod internal fixation system tested on a gap model construct.

OBJECTIVE: To compare the stiffness and strength of AO bone plates (DCP, LC-DCP, VCP, RCP, and LP) and the Clamp-Rod Internal Fixation System (CRIF). STUDY DESIGN: In vitro. SAMPLE SIZE: 12 individual implants of 18 plate dimensions and four sizes of CRIF, each corresponding to 2.0, 2.4/2.7, 3.5, or 4.5 mm screw sizes. METHODS: Implant-constructs of each plate and CRIF were created using Canevasit rods as a bone substitute in an unstable gap fracture model. Six implant-constructs of each type were tested under single cycle four-point bending loading, and six were tested under single cycle torsional loading until permanent plastic deformation occurred. RESULTS: Torsional stiffness and yield load of the DCP were always significantly greater than the CRIF within the same group. Bending properties of the 2.0 DCP were not significantly different to the 2.0 CRIF. The 2.7 DCP had significantly higher bending values than the 2.7 CRIF. The bending stiffness of the 3.5 DCP and 4.5 DCP was significantly less than their CRIF counterparts. While the bending yield load of the 3.5 DCP was significantly greater than the 3.5 CRIF, the bending yield load of the 4.5 DCP was significantly less than the 4.5 CRIF. CONCLUSION: A weakness was found in the torsional resistance of the CRIF constructs compared to the DCP constructs. CLINICAL SIGNIFICANCE: Bone holding power and applied screw torque should be considered when using the CRIF system in clinical application.

[Screw-in performance of threaded cups]. / Eindrehverhalten von Schraubpfannen.

INTRODUCTION: For threaded cups, cup diameter, the shape of the threads and the shape of the cup have a major influence on the screw-in performance. The designs of standard implants vary greatly, making it difficult to carry out comparative studies to provide clear-cut results on the effect of individual parameters on the insertion process. MATERIAL AND METHODS: 15 different prototype cups were manufactured for this study. Three sizes, three shapes and five thread designs were tested using artificial bone. Screw-in performance was measured with the slope of insertion torque before and after reaching the seating point, the torque at the seating point, the insertion angle and the change of slopes at the seating point. RESULTS: Modified trapezoid threads have the lowest insertion resistance and the clearest seating point as well as the most distinct change of slope at the seating point. Flat threads show lower insertion resistance and more increased slopes at the seating point than sharp threads. The slope of insertion torque before and at the seating point is higher for sharp threads in comparison to the other threads, the change of slop is however low. Larger cups show a higher insertion resistance. CONCLUSION: Screw-in performance is decisively influenced by the design of the threads. Modified trapezoid threads are the easiest to insert with excellent manual control, thus reducing the risk of intra-operative overturning. Flat threads also have a low screw-in resistance. Sharp threads have an unsatisfactory screw-in performance because the seating point cannot be "felt".

Archaea diversity within a commercial biogas plant utilizing herbal biomass determined by 16S rDNA and mcrA analysis.

AIMS: The Archaea diversity was evaluated in an agricultural biogas plant supplied with cattle liquid manure and maize silage under mesophilic conditions. METHODS AND RESULTS: Two different genes (16S rRNA; methyl-coenzyme-M-reductase, MCR) targeted by three different PCR primer sets were selected and used for the construction of three clone libraries comprising between 104 and 118 clones. The clone libraries were analysed by restriction fragment polymorphism (RFLP). Between 11 and 31 operational taxonomic units (OTUs) were detected and assigned to orders Methanomicrobiales, Methanosarcinales and Methanobacteriales. Over 70% of all Archaea OTUs belong to the order Methanomicrobiales which mostly include hydrogenotrophic methanogens. Acetotrophic methanogens were detected in minor rates. Similar relative values were obtained by a quantitative real-time PCR analysis. CONCLUSIONS: The results implied that in this biogas plant the most of the methane formation resulted from the conversion of H(2) and CO(2). SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports, for the first time, a molecular analysis of the archaeal community in this type of agricultural biogas plants. Therein the hydrogenotrophic methanogenesis seems to be the major pathway of methane formation. These results are in contrast with the common thesis that in biogas fermentations the primary substrate for methanogenesis is acetate.

Factors affecting the stability of screws in human cortical osteoporotic bone: a cadaver study.

We investigated several factors which affect the stability of cortical screws in osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96 years (mean 76). We performed bone densitometry to measure the bone mineral density of the cortical and cancellous bone of the shaft and head of the femur, respectively. The thickness and overall bone mass of the cortical layer of the shaft of the femur were measured using a microCT scanner. The force required to pull-out a 3.5 mm titanium cortical bone screw was determined after standardised insertion into specimens of the cortex of the femoral shaft. A significant correlation was found between the pull-out strength and the overall bone mass of the cortical layer (r(2) = 0.867, p < 0.01) and also between its thickness (r(2) = 0.826, p < 0.01) and bone mineral density (r(2) = 0.861, p < 0.01). There was no statistically significant correlation between the age of the donor and the pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral density (p = 0.697) or the level of osteoporosis (p = 0.378). We conclude that the overall bone mass, the thickness and the bone mineral density of the cortical layer, are the main factors which affect the stability of a screw in human female osteoporotic cortical bone.

["Cutting out" in pertrochanteric fractures--problem of osteoporosis?]. / "Cutting out" bei pertrochantären Frakturen -- ein Problem der Osteoporose?

BACKGROUND: Despite the use of intramedullary fixation devices for the stabilisation of intertrochanteric fractures, the rate of complications is still high. One of the main reasons for burdensome reinterventions in 9-15% of cases is the cutting out of the fixation device through both the spongious bone and the cortical bone at the apex of the femoral head. This phenomenon is strongly connected to the reduction of the fractures achieved, the technical performance of the operation with optimal implant positioning and the resistance of the trabecular bone in the femoral head against deformation by the fixation device. The latter is very low in cases of severe osteoporosis. To prevent the complication of cutting out, it seems sensible to find the limits of load-bearing capacity of individual osteoporosis-associated features (i.e. bone mineral density) at which special additional measures or other techniques for the treatment of these patients are desired. METHODS: In a first step a new biomechanical standard test for implants stabilizing unstable trochanteric fractures was developed, which would provide predictable results depending on bone mineral density. In a second step a cut-off limit was sought for the bone density in the proximal femur that would afford stable fixation as measured by QCT (quantitative computed tomography) and DEXA (dual-energy X-ray absorptiometry). RESULTS: The developed test is realistic; it can be used to study typical cutting out phenomena on cadaver femora. In an unstable fracture model (type A 2.3 of the AO classification), the implants DHS with TSP, PFN and TGN showed a stable long-term load-bearing capacity at a bone mineral density of >0.6 g/cm3. In 5 of 32 specimens a cutting out phenomenon could be demonstrated, in 4 cases if the bone mineral density of the proximal femur was below 0.6 g/cm3 as measured by DEXA, and in one case poor performance of the implant (short screw in the femoral head) was evident. CONCLUSIONS: In cases of bone density of >0.6 g/cm3 in the proximal femur (DEXA), the standard implants for the fixation of unstable trochanteric fractures could guarantee fixation without cutting out. The critical value of sufficient bone density in our few cases seems to be around 0.6 g/cm3 as measured by DEXA. Further investigation is needed to define the limits of bone mineral density for a successful osteosynthesis. An appropriate augmentation of the trabecular bone of the femoral head or a new design of the central loading device could increase the load-bearing capacity and thus help to reduce the cutting out phenomenon. Another alternative could be the primary implantation of an endoprosthesis in the treatment of these patients.

Osteosynthesis of supracondylar humerus fractures in children: a biomechanical comparison of four techniques.

BACKGROUND: Crossed k-wire osteosynthesis is a widely used procedure for displaced supracondylar humerus fractures in children, but the rate of secondary displacements is up to 31%. Alternative techniques including casts, elastic stable intramedullary nailing, and the fixateur extern, have been used, but there are no biomechanical data comparing these methods. We developed a biomechanical model to compare four osteosynthesis techniques for stabilizing supracondylar humerus fractures in children. METHODS: An osteotomy to simulate a fracture was made in a total of 32 adult cadaver humeri. The pseudofractures were then stabilized by crossed k-wires, elastic nailing, a fixateur extern with either k-wires, or Schanz screws. We measured the stiffness values in flexion and extension and torsion with static loading. The movements in cyclic loading were chosen to resemble the mechanism described in the development of a clinical cubitus varus. FINDINGS: No significant differences were found with static loading. With cyclic loading all methods showed an irreversible torsional deformation less than 20 degrees . Crossed k-wires and elastic nailing showed significantly lower reversible torsional deformation than the external fixateurs. INTERPRETATION: Our biomechanical data reveal that the crossed k-wires have the highest stiffness and lowest loss of reduction under cyclic loading. The external fixators proved to be good alternatives.

Reprogramming of root epidermal cells in response to nutrient deficiency.

Post-embryonic development of the root system is highly plastic to environmental cues, compensating for the sessile lifestyle of plants. The fate of epidermal cells of Arabidopsis roots is particularly responsive to nutritional signals, leading to an increase in the root's surface area in the absence of the essential but immobile minerals iron, phosphate and manganese. The resulting phenotype is characteristic of the respective condition. Growth under nutrient starvation affects the expression of genes involved in cell specification, indicating that environmental signals are perceived at an early stage of cell development. Cell fate decisions are controlled at different levels, probably integrated at the level of chromatin organization.

Osseointegration of hollow cylinder based spinal implants in normal and osteoporotic vertebrae: a sheep study.

INTRODUCTION: Osteoporosis is not only responsible for an increased number of metaphyseal and spinal fractures but it also complicates their treatment. To prevent the initial loosening, we developed a new implant with an enlarged implant/bone interface based on the concept of perforated, hollow cylinders. We evaluated whether osseointegration of a hollow cylinder based implant takes place in normal or osteoporotic bone of sheep under functional loading conditions during anterior stabilization of the lumbar spine. MATERIALS AND METHODS: Osseointegration of the cylinders and status of the fused segments (ventral corpectomy, replacement with iliac strut, and fixation with testing implant) were investigated in six osteoporotic (age 6.9 +/- 0.8 years, mean body weight 61.1 +/- 5.2 kg) and seven control sheep (age 6.1 +/- 0.2 years, mean body weight 64.9 +/- 5.7 kg). Osteoporosis was introduced using a combination protocol of ovariectomy, high-dose prednisone, calcium and phosphor reduced diet and movement restriction. Osseointegration was quantified using fluorescence and conventional histology; fusion status was determined using biomechanical testing of the stabilized segment in a six-degree-of-freedom loading device as well as with radiological and histological staging. RESULTS: Intact bone trabeculae were found in 70% of all perforations without differences between the two groups (P = 0.26). Inside the cylinders, bone volume/total volume was significantly higher than in the control vertebra (50 +/- 16 vs. 28 +/- 13%) of the same animal (P<0.01), but significantly less (P<0.01) than in the near surrounding (60 +/- 21%). After biomechanical testing as described in Sect. "Materials and methods", seven spines (three healthy and four osteoporotic) were classified as completely fused and six (four healthy and two osteoporotic) as not fused after a 4-month observation time. All endplates were bridged with intact trabeculae in the histological slices. CONCLUSIONS: The high number of perforations, filled with intact trabeculae, indicates an adequate fixation; bridging trabeculae between adjacent endplates and tricortical iliac struts in all vertebrae indicates that the anchorage is adequate to promote fusion in this animal model, even in the osteoporotic sheep.

Improved anchorage in osteoporotic vertebrae with new implant designs.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant.

BRIGEP--the BRIDGE-based genome-transcriptome-proteome browser.

The growing amount of information resulting from the increasing number of publicly available genomes and experimental results thereof necessitates the development of comprehensive systems for data processing and analysis. In this paper, we describe the current state and latest developments of our BRIGEP bioinformatics software system consisting of three web-based applications: GenDB, EMMA and ProDB. These applications facilitate the processing and analysis of bacterial genome, transcriptome and proteome data and are actively used by numerous international groups. We are currently in the process of extensively interconnecting these applications. BRIGEP was developed in the Bioinformatics Resource Facility of the Center for Biotechnology at Bielefeld University and is freely available. A demo project with sample data and access to all three tools is available at https://www.cebitec.uni-bielefeld.de/groups/brf/software/brigep/. Code bundles for these and other tools developed in our group are accessible on our FTP server at ftp.cebitec.uni-bielefeld.de/pub/software/.

Aspects of internal fixation of fractures in porotic bone. Principles, technologies and procedures using locked plate screws.

Fractures of the bones of elderly people occur more often and have a more important effect because of a generally diminished ability to coordinate stance and walking. These fractures occur at a lower level of load because of lack of strength of the porotic bone. Prompt recovery of skeletal support function is essential to avoid respiratory and circulatory complications in the elderly. To prevent elderly people from the risks of being bedridden, demanding internal fixation of fractures is required. The weak porotic bone and the high level of uncontrolled loading after internal fixation pose complex problems. A combination of several technical elements of design, application and aftercare in internal fixation are proposed. Internal fixators with locked screws improve the biology and the mechanics of internal fixation. When such fixators are used as elevated splints they may stimulate early callus formation because of their flexibility, the limit of flexibility being set by the demands of resistance and function of the limb. Our own studies of triangulation of locked screws have demonstrated their beneficial effects and unexpected limitations.

Correlation of biomechanical stiffness with plain radiographic and ultrasound data in an experimental mandibular distraction wound.

The aim of this study was to determine the stiffness of a porcine mandibular distraction wound at the end of neutral fixation.Twenty-four Yucatan minipigs underwent unilateral mandibular distraction: zero-day latency, rates of 1, 2, and 4 mm per day, distraction gap of 12 mm. Radiographic and ultrasound bone fill scores at 0, 8, 16 and 24 days of neutral fixation were used to evaluate interval healing. At sacrifice, biomechanical stiffness was determined using an Instron machine to produce a downward force of 2 mm/min at the premolar occlusal surface. Force (kilo-Newton, kN) and displacement (mm) were recorded at a rate of 10,000 points/second. Stiffness across the distraction wound, plain radiographic and ultrasound bone fill scores all increased with duration of neutral fixation and were highest for the 1 mm per day group at all time points. At the end of fixation, even in the most clinically stable group, stiffness across the distraction wound was only 25.5% of control.Despite clinical stability and high bone fill scores by X-ray and ultrasound, the distraction wound did not achieve normal stiffness at the end of neutral fixation in this model. This may have implications for the management of patients who undergo large movements by distraction.

Development of a mechanical testing system for a mandibular distraction wound.

The purpose of this study was to develop a mechanical testing system to estimate stiffness of an experimental porcine mandibular distraction osteogenesis (DO) wound. The system was designed to function without changing the morphology of the healing mandible. A customized jig was designed to allow cantilever-bending tests of the Yucatan mini-pig hemi-mandible. Experimental and control hemi-mandibles were placed in the jig and the proximal segment was secured. A material testing unit applied progressively increasing downward force on the pre-molar occlusal surface. The maximum force applied was 0.030 kN. The stiffness value for each hemi-mandible was represented by the slope of the plot of force (kN) vs displacement (mm). Radiographs were taken before and after mechanical testing to demonstrate any gross morphologic changes or identifiable fractures across the distraction wound. A total of 24 mini-pigs underwent DO of the right mandible with 0-day latency and distraction rates of 1, 2, and 4 mm per day resulting in a 12 mm gap. At the completion of 0, 8, 16, and 24 days of neutral fixation, two animals for each of three different distraction rates were sacrificed for mechanical testing. Stiffness of control hemi-mandibles ranged between 0.018 and 0.317 kN/mm (median 0.063; mean 0.099 +/- 0.080). Stiffness of experimental hemi-mandibles ranged between 0 and 0.025 kN/mm (median 0.004; mean 0.005). The subset that was tested at the end of neutral fixation had stiffness between 0.005 and 0.025 (median 0.011; mean 0.012 +/- 0.011). No morphologic changes were evident on the X-rays after testing. The results indicate that the cantilever-bending model is useful for testing stiffness of an experimental mandibular DO wound without destroying its morphology.