Quantitative morphology of the subchondral plate of the tibial plateau

The object of the present investigation was to measure the thickness distribution of the subchondral plate of the tibial plateau. The data were obtained by computerised image analysis of serial sections. The measured values revealed a marked difference in the thickness between the various regions of the joint surface. Thinner zones (100-300 microns) are found in the peripheral region near the margin of the tibial plateau. Thickness maxima (up to 1500 microns and more) are to be seen at the centres of the joint surfaces. The relationship between the thickness distribution of the subchondral plate and information about the stress distribution of this particular joint surface support the conclusion that the morphology of the subchondral plate of the tibial plateau is determined by the function of the joint

Physiological incongruity of the humero-ulnar joint

Investigations into the distribution of subchondral bone density in the human elbow have suggested that the geometry of the trochlear notch deviates from a perfect fit with the trochlea, and that the load is transmitted ventrally and dorsally rather than through the centre of the humero-ulnar joint. We therefore decided to make a quantitative assessment of the degree of incongruity between the two components in 15 human specimens (age distribution 60 to 93 years) with different types of joint surface. Polyether casts of the joint cavity were prepared under loads of 10,40,160 and 640 N. The thickness of the casts was then measured at 50 predetermined points, and an area distribution of the width of the joint space represented in a two-dimensional template of the trochlear notch. The reproducibility of this procedure was tested by image analysis. At a load of 10 N, only a narrow space was present ventrally and dorsally in the joint, but in the depths of the trochlear notch a width of 0.5 to 1 mm was recorded in the centre, and up to 3 mm at its medial and lateral edges. Specimens with continuous articular cartilage showed a lower degree of incongruity than those with a divided articular surface. As the load was increased to 640 N, however, the original incongruity between the articular surfaces disappeared almost completely. The joint surfaces became more congruous, probably because of the viscoelastic properties of the articular cartilage and the subchondral bone, and the contact areas merged in the centre of the joint. It is suggested that this physiological incongruity brings about an optimal distribution of stress over the articular surface during the transmission of the load, and it may lead to better nourishment of the articular cartilage by providing intermittent mechanical stimulation and circulation of the synovial fluid

Dose-dependent new bone formation by extracorporeal shock wave application on the intact femur of rabbits

Background: Whereas various molecular working mechanisms of shock waves have been demonstrated, no study has assessed in detail the influence of varying energy flux densities (EFD) on new bone formation in vivo. Methods: Thirty Chinchilla bastard rabbits were randomly assigned to 5 groups (EFD 0.0, 0.35, 0.5, 0.9 and 1.2 mJ/mm(2)) and treated with extracorporeal shock waves at the distal femoral region (1,500 pulses; 1 Hz frequency). To investigate new bone formation, animals were injected with oxytetracycline at days 5-9 after shock wave application and sacrificed on day 10. Histological sections of all animals were examined using broad-band epifluorescent illumination, contact microradiography and Giemsa-Eosin staining. Results: Application of shock waves induced new bone formation beginning with 0.5 mJ/mm(2) EFD and increasing with 0.9 mJ/mm(2) and 1.2 mJ/mm(2). The latter EFD resulted in new bone formation also on the dorsal cortical bone; cortical fractures and periosteal detachment also occurred. Conclusion: Here, for the first time, a threshold level is presented for new bone formation after applying shock waves to intact bone in vivo. The findings of this study are of considerable significance for preventing unwanted side effects in new approaches in the clinical application of shock waves. Copyright (c) 2008 S. Karger AG, Basel

The cross-frequency mediation mechanism of intracortical information transactions

In a seminal paper by von Stein and Sarnthein (2000), it was hypothesized that "bottom-up" information processing of "content" elicits local, high frequency (beta-gamma) oscillations, whereas "top-down" processing is "contextual", characterized by large scale integration spanning distant cortical regions, and implemented by slower frequency (theta-alpha) oscillations. This corresponds to a mechanism of cortical information transactions, where synchronization of beta-gamma oscillations between distant cortical regions is mediated by widespread theta-alpha oscillations. It is the aim of this paper to express this hypothesis quantitatively, in terms of a model that will allow testing this type of information transaction mechanism. The basic methodology used here corresponds to statistical mediation analysis, originally developed by (Baron and Kenny 1986). We generalize the classical mediator model to the case of multivariate complex-valued data, consisting of the discrete Fourier transform coefficients of signals of electric neuronal activity, at different frequencies, and at different cortical locations. The "mediation effect" is quantified here in a novel way, as the product of "dual frequency RV-coupling coefficients", that were introduced in (Pascual-Marqui et al 2016, http://arxiv.org/abs/1603.05343). Relevant statistical procedures are presented for testing the cross-frequency mediation mechanism in general, and in particular for testing the von Stein & Sarnthein hypothesis.Comment: https://doi.org/10.1101/119362 licensed as CC-BY-NC-ND 4.0 International license: http://creativecommons.org/licenses/by-nc-nd/4.0

Differentially expressed microRNAs in maternal plasma for the noninvasive prenatal diagnosis of Down syndrome (trisomy 21).

OBJECTIVES: Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies. METHODS: Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls. RESULTS: Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially expressed mature miRNAs were identified as potential biomarkers. Hierarchical cluster analysis of these miRNAs resulted in the clear discrimination of DS from euploid pregnancies. Gene targets of the differentially expressed miRNAs were enriched in signaling pathways such as mucin type-O-glycans, ECM-receptor interactions, TGF-beta, and endocytosis, which have been previously associated with DS. CONCLUSIONS: miRNAs are promising and stable biomarkers for a broad range of diseases and may allow a reliable, cost-efficient diagnostic tool for the noninvasive prenatal diagnosis of DS

The innervation of the enthesis organ of the rat achilles tendon

PURPOSE: The enthesis (bony insertion of a tendon or ligament) is a common site of overuse injuries in sport. Because enthesopathies can be painful, it is often assumed that the enthesis is highly innervated-but with little evidence to support the assumption. The Achilles tendon has one of the most complex of attachment sites, for together with adjacent tissues, the enthesis itself forms part of an 'enthesis organ' which reduces stress concentration at the bony interface. These adjacent structures include a 'sesamoid fibrocartilage' in the tendon, a 'periosteal fibrocartilage' on the superior tuberosity of the calcaneus, and a fat pad which extends into the retrocalcaneal bursa during plantarflexion. The purpose of the present study is to investigate the innervation of the whole enthesis organ complex. METHODS: The tendon attachment site was removed from one leg of 3 male Wistar rats at each of the following ages-neonates, 4 weeks, 12 weeks, and 24 months. The tissue was fixed in 4% paraformaldehyde, prepared for routine indirect immunohistochemistry and cryosectioned in the sagittal plane. Serial sections were immunolabelled with polyclonal antibodies to protein gene product 9.5, substance P, calcitonin gene related peptide and neurofilament 200. Histology reference sections were stained with toluidine blue. RESULTS: No nerve fibers were detected at the enthesis itself or in the sesamoid and periosteal fib ro cartilages in rats of any age. However, the fat pad was richly supplied by nerve fibers which immunolabelled with all of the antibodies used. It also contained abundant mast cells. The innervation of the fat pad was confirmed in 10 human Achilles tendons obtained from the Department of Forensic Medicine at the Ludwig-Maximilians-Universität, in accordance with the ethical regulations of Munich University. The nerve fibers again immunolabelled with all antibodies and formed an intricate network in which the fibers lay between individual fat cells. CONCLUSION: We suggest that healthy entheses are not innervated because of the high levels of mechanical loading experienced at insertion sites. However, the striking innervation of the adjacent fat pad suggests that it may have an unheralded proprioceptive role monitoring changes in insertional angle between tendon and bone that occur as a result of foot movements

A novel implantation technique for engineered osteo-chondral grafts

We present a novel method to support precise insertion of engineered osteochondral grafts by pulling from the bone layer, thereby minimizing iatrogenic damage associated with direct manipulation of the cartilage layer. Grafts were generated by culturing human expanded chondrocytes on Hyaff®-11 meshes, sutured to Tutobone® spongiosa cylinders. Through the bone layer, shaped to imitate the surface-contours of the talar dome, two sutures were applied: the first for anterograde implantation, to pull the graft into the defect, and the second for retrograde correction, in case of a too deep insertion. All grafts could be correctly positioned into osteochondral lesions created in cadaveric ankle joints with good fit to the surrounding cartilage. Implants withstood short-term dynamic stability tests applied to the ankle joint, without delamination or macroscopic damage. The developed technique, by allowing precise and stable positioning of osteochondral grafts without iatrogenic cartilage damage, is essential for the implantation of engineered tissues, where the cartilage layer is not fully mechanically developed, and could be considered also for conventional autologous osteochondral transplantatio

Completely positive divisibility does not mean markovianity

In the classical domain, it is well known that divisibility does not imply that a stochastic process is Markovian. However, for quantum processes, divisibility is often considered to be synonymous with Markovianity. We show that completely positive divisible quantum processes can still involve non-Markovian temporal correlations, that we then fully classify using the recently developed process tensor formalism, which generalizes the theory of stochastic processes to the quantum domain