A conceptual model of compensation/decompensation in lumbar segmental instability

Lumbar spinal instability (LSI) is a common spinal disorder and can be associated with substantial disability. The concept of defining clinically relevant classifications of disease or 'target condition' is used in diagnostic research. Applying this concept to LSI we hypothesize that a set of clinical and radiological criteria can be developed to identify patients with this target condition who are at high risk of 'irreversible' decompensated LSI for whom surgery becomes the treatment of choice. In LSI, structural deterioration of the lumbar disc initiates a degenerative cascade of segmental instability. Over time, radiographic signs become visible: traction spurs, facet joint degeneration, misalignment, stenosis, olisthesis and de novo scoliosis. Ligaments, joint capsules, local and distant musculature are the functional elements of the lumbar motion segment. Influenced by non-functional factors, these functional elements allow a compensation of degeneration of the motion segment. Compensation may happen on each step of the degenerative cascade but cannot reverse it. However, compensation of LSI may lead to an alleviation or resolution of clinical symptoms. In return, the target condition of decompensation of LSI may cause the new occurrence of symptoms and pain. Functional compensation and decompensation are subject to numerous factors that can change which makes estimation of an individual's long-term prognosis difficult. Compensation and decompensation may influence radiographic signs of degeneration, e.g. the degree of misalignment and segmental angulation caused by LSI is influenced by the tonus of the local musculature. This conceptual model of compensation/decompensation may help solve the debate on functional and psychosocial factors that influence low back pain and to establish a new definition of non-specific low back pain. Individual differences of identical structural disorders could be explained by compensated or decompensated LSI leading to changes in clinical symptoms and pain. Future spine surgery will have to carefully define and measure functional aspects of LSI, e.g. to identify a point of no return where multidisciplinary interventions do not allow a re-compensation and surgery becomes the treatment of choice.

Quarks and a Unified Theory of Nature Fundamental Forces

Quarks were introduced 50 years ago opening the road towards our understanding of the elementary constituents of matter and their fundamental interactions. Since then, a spectacular progress has been made with important discoveries that led to the establishment of the Standard Theory that describes accurately the basic constituents of the observable matter, namely quarks and leptons, interacting with the exchange of three fundamental forces, the weak, electromagnetic and strong force. Particle physics is now entering a new era driven by the quest of understanding of the composition of our Universe such as the unobservable (dark) matter, the hierarchy of masses and forces, the unification of all fundamental interactions with gravity in a consistent quantum framework, and several other important questions. A candidate theory providing answers to many of these questions is string theory that replaces the notion of point particles by extended objects, such as closed and open strings. In this short note, I will give a brief overview of string unification, describe in particular how quarks and leptons can emerge and discuss what are possible predictions for particle physics and cosmology that could test these ideas.

Quarks and a unified theory of Nature fundamental forces

Quarks were introduced 50 years ago opening the road towards our understanding of the elementary constituents of matter and their fundamental interactions. Since then, a spectacular progress has been made with important discoveries that led to the establishment of the Standard Theory that describes accurately the basic constituents of the observable matter, namely quarks and leptons, interacting with the exchange of three fundamental forces, the weak, electromagnetic and strong force. Particle physics is now entering a new era driven by the quest of understanding of the composition of our Universe such as the unobservable (dark) matter, the hierarchy of masses and forces, the unification of all fundamental interactions with gravity in a consistent quantum framework, and several other important questions. A candidate theory providing answers to many of these questions is string theory that replaces the notion of point particles by extended objects, such as closed and open strings. In this short note, I will give a brief overview of string unification, describe in particular how quarks and leptons can emerge and discuss what are possible predictions for particle physics and cosmology that could test these ideas.

Neurogenic thoracic outlet syndrome due to subclavius posticus muscle with dynamic brachial plexus compression: a case report.

BACKGROUND Neurogenic thoracic outlet syndrome is an underestimated cause of brachial weakness and pain. The subclavius posticus muscle (SPM) is an aberrant muscle originating from the medial aspect of the first rib reaching to superior border of the scapula, which may cause, depending on its activation, dynamic compression of the brachial plexus. CASE PRESENTATION In the present study, we report about a 32-year-old male caucasian patient with weakness in radial deviation of his left hand. An isolated macrodactyly of his left middle finger had been operated twice. Electroneurography showed a carpal-tunnel-syndrome (CTS) on the left side. MRI of the brachial plexus revealed an additional muscle in the costoclavicular space, identified as SPM. To our knowledge, this is the second case report of a neurogenic thoracic outlet syndrome due to SPM, and the first case described with isolated macrodactyly and CTS in the same patient. CONCLUSION If complaints about hand weakness are only reported in cases of distinct hand positions, a dynamic compression of the brachial plexus by SPM may be the cause. A neurogenic thoracic outlet syndrome may facilitate the development of CTS.

Acupuncture-induced changes of pressure pain threshold are mediated by segmental inhibition-a randomized controlled trial

Our aim was to distinguish between spinal and supraspinal mechanisms in the intact nervous system by comparing homosegmental and heterosegmental effects of electroacupuncture (EA) and manual acupuncture (MA) on sensory perception in healthy volunteers by means of quantitative sensory testing. Seventy-two healthy volunteers were randomly assigned to receive either MA or EA at SP 6, SP 9, GB 39, and ST 36 at the left leg or relaxed for 30 minutes (control group [CG]). Blinded examiners assessed 13 sensory modalities (thermal and mechanical detection and pain thresholds) at the upper arms and lower legs before and after intervention by means of a standardized quantitative sensory testing battery. Change scores of all 13 sensory thresholds were compared between groups. The main outcome measure was the change score of the pressure pain threshold (PPT). There were no baseline differences between groups. Pressure pain threshold change scores at the lower left leg, in the same segment as the needling site, differed significantly (P = 0.008) between the EA (median: 103.01 kPa) and CG groups (median: 0.00 kPa) but not between the MA (median: 0.00 kPa) and CG groups. No further significant change score differences were found between one of the acupuncture groups and the CG. The PPT can be changed by EA. The PPT increase was confined to the segment of needling, which indicates that it is mainly mediated by segmental inhibition in the spinal cord. This underscores the importance of segmental needling and electrical stimulation in clinical practice.

Continuum damage interactions between tension and compression in osteonal bone

Skeletal diseases such as osteoporosis impose a severe socio-economic burden to ageing societies. Decreasing mechanical competence causes a rise in bone fracture incidence and mortality especially after the age of 65 y. The mechanisms of how bone damage is accumulated under different loading modes and its impact on bone strength are unclear. We hypothesise that damage accumulated in one loading mode increases the fracture risk in another. This study aimed at identifying continuum damage interactions between tensile and compressive loading modes. We propose and identify the material constants of a novel piecewise 1D constitutive model capable of describing the mechanical response of bone in combined tensile and compressive loading histories. We performed several sets of loading–reloading experiments to compute stiffness, plastic strains, and stress-strain curves. For tensile overloading, a stiffness reduction (damage) of 60% at 0.65% accumulated plastic strain was detectable as stiffness reduction of 20% under compression. For compressive overloading, 60% damage at 0.75% plastic strain was detectable as a stiffness reduction of 50% in tension. Plastic strain at ultimate stress was the same in tension and compression. Compression showed softening and tension exponential hardening in the post-yield regime. The hardening behaviour in compression is unaffected by a previous overload in tension but the hardening behaviour in tension is affected by a previous overload in compression as tensile reloading strength is significantly reduced. This paper demonstrates how damage accumulated under one loading mode affects the mechanical behaviour in another loading mode. To explain this and to illustrate a possible implementation we proposed a theoretical model. Including such loading mode dependent damage and plasticity behaviour in finite element models will help to improve fracture risk analysis of whole bones and bone implant structures.

The influence of different osteosynthesis configurations with locking compression plates (LCP) on stability and fracture healing after an oblique 45° angle osteotomy

Background Locking compression plates are used in various configurations with lack of detailed information on consequent bone healing. Study design In this in vivo study in sheep 5 different applications of locking compression plate (LCP) were tested using a 45° oblique osteotomy simulating simple fracture pattern. 60 Swiss Alpine sheep where assigned to 5 different groups with 12 sheep each (Group 1: interfragmentary lag screw and an LCP fixed with standard cortex screws as neutralisation plate; Group 2: interfragmentary lag screw and LCP with locking head screws; Group 3: compression plate technique (hybrid construct); Group 4: internal fixator without fracture gap; Group 5: internal fixator with 3 mm gap at the osteotomy site). One half of each group (6 sheep) was monitored for 6 weeks, and the other half (6 sheep) where followed for 12 weeks. Methods X-rays at 3, 6, 9 and 12 weeks were performed to monitor the healing process. After sacrifice operated tibiae were tested biomechanically for nondestructive torsion and compared to the tibia of the healthy opposite side. After testing specimens were processed for microradiography, histology, histomorphometry and assessment of calcium deposition by fluorescence microscopy. Results In all groups bone healing occurred without complications. Stiffness in biomechanical testing showed a tendency for higher values in G2 but results were not statistically significant. Values for G5 were significantly lower after 6 weeks, but after 12 weeks values had improved to comparable results. For all groups, except G3, stiffness values improved between 6 and 12 weeks. Histomorphometrical data demonstrate endosteal callus to be more marked in G2 at 6 weeks. Discussion and conclusion All five configurations resulted in undisturbed bone healing and are considered safe for clinical application.

Inference of evolutionary forces acting on human biological pathways

Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures.

Lordoplasty: midterm outcome of an alternative augmentation technique for vertebral fractures.

OBJECTIVE Vertebroplasty and balloon kyphoplasty are effective treatment options for osteoporotic vertebral compression fractures but are limited in correction of kyphotic deformity. Lordoplasty has been reported as an alternative, cost-effective, minimally invasive, percutaneous cement augmentation technique with good restoration of vertebral body height and alignment. The authors report on its clinical and radiological midterm results. METHODS A retrospective review was conducted of patients treated with lordoplasty from 2002 to 2014. Inclusion criteria were clinical and radiological follow-up evaluations longer than 24 months. Radiographs were accessed regarding initial correction and progressive loss of reduction. Complications and reoperations were recorded. Actual pain level, pain relief immediately after surgery, autonomy, and subjective impression of improvement of posture were assessed by questionnaire. RESULTS Sixty-five patients (46 women, 19 men, age range 38.9-86.2 years old) were treated with lordoplasty for 69 vertebral compression and insufficiency fractures. A significant correction of the vertebral kyphotic angle (mean 13°) and segmental kyphotic angle (mean 11°) over a mean follow-up of 33 months (range 24-108 months) was achieved (p < 0.001). On average, pain was relieved to 90% of the initial pain level. In 24% of the 65 patients a second spinal intervention was necessary: 16 distant (24.6%) and 7 adjacent (10.8%) new osteoporotic fractures, 4 instrumented stabilizations (6.2%), 1 new adjacent traumatic fracture (1.5%), and 1 distant microsurgical decompression (1.5%). Cement leakage occurred in 10.4% but was only symptomatic in 1 case. CONCLUSIONS Lordoplasty appeared safe and effective in midterm pain alleviation and restoration of kyphotic deformity in osteoporotic compression and insufficiency fractures. The outcomes of lordoplasty are consistent with other augmentation techniques.

Bufferless Compression of Asynchronously Sampled ECG Signals in Cubic Hermitian Vector Space.

Asynchronous level crossing sampling analog-to-digital converters (ADCs) are known to be more energy efficient and produce fewer samples than their equidistantly sampling counterparts. However, as the required threshold voltage is lowered, the number of samples and, in turn, the data rate and the energy consumed by the overall system increases. In this paper, we present a cubic Hermitian vector-based technique for online compression of asynchronously sampled electrocardiogram signals. The proposed method is computationally efficient data compression. The algorithm has complexity O(n), thus well suited for asynchronous ADCs. Our algorithm requires no data buffering, maintaining the energy advantage of asynchronous ADCs. The proposed method of compression has a compression ratio of up to 90% with achievable percentage root-mean-square difference ratios as a low as 0.97. The algorithm preserves the superior feature-to-feature timing accuracy of asynchronously sampled signals. These advantages are achieved in a computationally efficient manner since algorithm boundary parameters for the signals are extracted a priori.

Genetically engineered silk and genipin-enhanced fibrin hydrogel for annulus fibrosus repair

INTRODUCTION: Around 80% of people are affected by low back pain at least once in their life, often caused by trauma provoking intervertebral disc (IVD) herniation and/or IVD degeneration. Apart from some promising approaches for nucleus pulposus repair, so far no treatment or repair is available for the outer fibrous tissue, annulus fibrosus (AF). We aimed for sealing and repairing an AF injury in a bovine IVD organ culture model in vitro over 14 days under different loading conditions. For this purpose, a silk fleece composite from Bombyx mori silk was combined with genipin-enhanced fibrin hydrogel [1]. METHODS: Bovine IVDs of 12-17 months old animals were isolated by first removing all surrounding tissue, followed by cutting out the IVDs [2]. Culturing of discs occurred in high glucose Dulbecco's Modified Eagle Medium (HG-DMEM) supplemented with 5% serum as previously described. On the next day, injury was induced using a 2mm biopsy punch (Polymed, Switzerland). The formed cavity was filled with (0.4%) genipin-enhanced human based fibrin hydrogel (35- 55mg/mL human fibrinogen, Baxter, Austria) and sealed with a silk fleece-membrane composite (Spintec Engineering, Germany). Different culture conditions were applied: free swelling, static diurnal load of 0.2MPa for 8h/d and complex loading at 0.2MPa compression combined with ± 2° torsion at 0.2Hz for 8h/d. Complex loading was applied by a custom built 2 degree of freedom bioreactor [3]. After 14 days of culture cell activity was determined with resazurin assay. Additionally, glycosaminoglycan (dimethyl-methylene blue), DNA (Hoechst) and collagen content (hydroxy-proline) were determined. Finally, real-time qPCR of major IVD marker genes was performed. RESULTS: The silk seal closing the injury site could successfully withstand the forces of all three loading conditions with no misplacement over the two weeks’ culture. Nevertheless, disc height of the repaired discs did not significantly differ from the injured group. The disc phenotype could be maintained as demonstrated by biochemical analysis of gene expression, cell activity, DNA-, collagen- and GAG content. The silk itself was evaluated to be highly biocompatible for hMSC, as revealed by cytotoxicity assays. DISCUSSION & CONCLUSIONS: The silk can be considered a highly-elastic and biocompatible material for AF closure and the genipin-enhanced fibrin hydrogel has also good biomechanical properties. However, the cyto-compatibility of genipin seems rather poor and other hydrogels and/or cross-linkers should be looked into. REFERENCES: 1 C.C. Guterl et al. (2014) Characterization of Mechanics and Cytocompatibility of Fibrin Genipin Annulus Fibrosus Sealant with the Addition of Cell Adhesion Molecules, Tissue Eng Part A 2 S.C. Chan, B. Gantenbein-Ritter (2012) Preparation of intact bovine tail intervertebral discs for organ culture, J Vis Exp 3 B Gantenbein et al. (2015) Organ Culture Bioreactors - Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy, Curr Stem Cell Res Ther [epub ahead of print] ACKNOWLEDGEMENTS: This project is supported by the Gebert Rüf Stiftung project # GRS-028/13.

Compression Loading Induced Cellular Stress Response of Intervertebral Disc Cells in Organ Culture

Introduction: Mechanical stress is often associated to interverterbal disc (IVD) degeneration and the effect of mechanical loading on IVD has been studied and reviewed.1,2 Previously, expression of heat shock proteins, HSP70 and HSP27 has been found in pathological discs.3 However, there is no direct evidence on whether IVD cells respond to the mechanical loading by expression of HSPs. The objective of this study is to investigate the stress response of IVD cells during compressive loading in an organ culture. Materials and Methods: Fresh adult bovine caudal discs were cultured with compressive loading applied at physiological range. Effect of loading type (static and dynamic) and repeated loading (2 hours per day for 2 days) were studied. Nucleus pulposus (NP) and annulus fibrosus (AF) of the IVD were retrieved at different time points: right after loading and right after resting. Positive control discs were heat shocked (43°C). Cell activity was assessed and expression of stress response genes (HSP70 and HSF1) and matrix remodeling genes (ACAN, COL2, COL1, ADAMTS4, MMP3 and MMP13) were studied. Results: Cell activity was maintained in all groups. Both NP and AF expressed high level of HSP70 in heat shock groups, confirming their expression in response to stress. In NP, expression of HSP70 was up-regulated after static loading and dynamic loading with higher fold change was observed after static loading. During repeated loading, HSP70 appeared to be upregulated right after loading and decreased after resting. Such trend was not observed in AF and HSF1 levels. Expressions of matrix remodeling genes did not change significantly with loading except ADAMTS4 decreased in AF during static loading. Conclusion: This study demonstrated that NP cells upregulate expression of HSP70 in response to loading induced stress without changing cell activity and matrix remodeling significantly. Acknowledgments: This project was funded by AO Spine (AOSPN) (grant number: SRN_2011_14) and a fellowship exchange award by AO Spine Scientific Research Network (SRN).