The effects of dynamic loading on the intervertebral disc

Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

Dynamic Web Development with Seaside

Seaside is the open source framework of choice for developing sophisticated and dynamic web applications. Seaside uses the power of objects to master the web. With Seaside web applications is as simple as building desktop applications. Seaside lets you build highly dynamic and interactive web applications. Seaside supports agile development through interactive debugging and unit testing. Seaside is based on Smalltalk, a proven and robust language implemented by different vendors. Seaside is now available for all the major Smalltalk including Pharo, Squeak, GNU Smalltalk, Cincom Smalltalk, GemStone Smalltalk, and VA Smalltalk.

Comparison of tendency-oriented perimetry and dynamic strategy in octopus perimetry as a screening tool in a clinical setting: a prospective study

OBJECTIVE: The aim of this study was to compare the results of tendency-oriented perimetry (TOP) and a dynamic strategy in octopus perimetry as screening methods in clinical practice. DESIGN: A prospective single centre observational case series was performed. PARTICIPANTS AND METHODS: In a newly opened general ophthalmologic practice 89 consecutive patients (171 eyes) with a clinical indication for octopus static perimetry testing (ocular hypertension or suspicious optic nerve cupping) were examined prospectively with TOP and a dynamic strategy. The visual fields were graded by 3 masked observers as normal, borderline or abnormal without any further clinical information. RESULTS: 83% eyes showed the same result for both strategies. In 14% there was a small difference (with one visual field being abnormal or normal, the other being borderline). In only 2.9% of the eyes (5 cases) was there a contradictory result. In 4 out of 5 cases the dynamic visual field was abnormal and TOP was normal. 4 of these cases came back for a second examination. In all 4 the follow-up examination showed a normal second dynamic visual field. CONCLUSIONS: Octopus static perimetry using a TOP strategy is a fast, patient-friendly and very reliable screening tool for the general ophthalmological practice. We found no false-negative results in our series.

Performance of vertebral cancellous bone augmented with compliant PMMA under dynamic loads

Increased fracture risk has been reported for the adjacent vertebral bodies after vertebroplasty. This increase has been partly attributed to the high Young's modulus of commonly used polymethylmethacrylate (PMMA). Therefore, a compliant bone cement of PMMA with a bulk modulus closer to the apparent modulus of cancellous bone has been produced. This compliant bone cement was achieved by introducing pores in the cement. Due to the reduced failure strength of that porous PMMA cement, cancellous bone augmented with such cement could deteriorate under dynamic loading. The aim of the present study was to assess the potential of acute failure, particle generation and mechanical properties of cancellous bone augmented with this compliant cement in comparison to regular cement. For this purpose, vertebral biopsies were augmented with porous- and regular PMMA bone cement, submitted to dynamic tests and compression to failure. Changes in Young's modulus and height due to dynamic loading were determined. Afterwards, yield strength and Young's modulus were determined by compressive tests to failure and compared to the individual composite materials. No failure occurred and no particle generation could be observed during dynamical testing for both groups. Height loss was significantly higher for the porous cement composite (0.53+/-0.21%) in comparison to the biopsies augmented with regular cement (0.16+/-0.1%). Young's modulus of biopsies augmented with porous PMMA was comparable to cancellous bone or porous cement alone (200-700 MPa). The yield strength of those biopsies (21.1+/-4.1 MPa) was around two times higher than for porous cement alone (11.6+/-3.3 MPa).

Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA)

OBJECTIVE Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). METHODS We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. RESULTS Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. CONCLUSION DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2-hypersignal, on a numeric scale allowing for a more subtle grading of MS-lesions.

Synthesis and testing of photoaffinity probes for the site-selectivechemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.1 It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photophores via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photolabile moieties that show nanomolar binding affinities for the orthosteric binding site. Furthermore we established a stable h5-HT3R expressing cell line and a purification protocol to yield the receptor in a high purity. Currently we are investigating the photo crosslinking of these ligands with the 5-HT3R.

Synthesis and testing of photoaffinity probes for the site-selective chemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.[1] It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photolabile building blocks via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photo-labile moieties that show nanomolar binding affinities for the orthosteric binding site. Further on we developed a stable 5-HT3R overexpressing cell line and a purification method to yield the receptor in a high purity. Currently we are investigating crosslinking experiments and subsequent MS – analysis.

Synthesis and testing of photoaffinity probes for the site-selectivechemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.1 It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photophores via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photolabile moieties that show nanomolar binding affinities for the orthosteric binding site. Furthermore we established a stable h5-HT3R expressing cell line and a purification protocol to yield the receptor in a high purity. Currently we are investigating the photo crosslinking of these ligands with the 5-HT3R.

Synthesis and testing of photoaffinity probes for the site-selective chemical modifications of the 5-HT3 receptor

The 5-HT3 receptor (5-HT3R) is an important ion channel responsible for the transmission of nerve impulses in the central nervous system.1 It is difficult to characterize transmembrane dynamic receptors with classical structural biology approaches like crystallization and x-ray. The use of photoaffinity probes is an alternative approach to identify regions in the protein that are important for the binding of small molecules. Therefore we synthesized a small library of photoaffinity probes by conjugating photophores via various linkers to granisetron which is a known antagonist of the 5-HT3R. We were able to obtain several compounds with diverse linker lengths and different photolabile moieties that show nanomolar binding affinities for the orthosteric binding site. Furthermore we established a stable h5-HT3R expressing cell line and a purification protocol to yield the receptor in a high purity. Currently we are investigating the photo crosslinking of these ligands with the 5-HT3R.

Dynamic intraligamentary stabilization and primary repair: A new concept for the treatment of knee dislocation.

BACKGROUND Traumatic knee dislocation represents a rare but devastating injury. Several controversies persist regarding type of treatment, surgical timing, graft selection, repair versus reconstruction of the medial and lateral structures, surgical techniques and postoperative rehabilitation. A new technique for primary ACL stabilization, dynamic intaligamentary stabilization (DIS) was developed at the authors' institution. The purpose of this study was to analyze the clinical and radiological outcomes of surgically treated traumatic knee dislocations by means of the DIS technique for the ACL, primary suturing for PCL, MCL and LCL. METHODS Between 2009 and 2012, 35 patients treated surgically for traumatic knee dislocation with primary anterior cruciate ligament (ACL) reconstruction with DIS, suturing of the posterior cruciate ligament (PCL) and primary complete repair of collaterals, were evaluated clinically (IKDC score, SF12 health survey, Lysholm score, Tegner score) and radiologically with a mean follow up of 2.2 years (range 1.00-3.50 years) years. Instrumented anterior-posterior translation was measured (KT-2000). RESULTS Anterior/posterior translation (KT-2000) for the healthy and injured limb was 4.8mm (range 3-8mm) and 7.3mm (range 5-10) (89N) respectively. Valgus and varus stress testing in 30° flexion was normal in 26 (75%) and 29 (83%) patients, respectively. The IKDC score was B in 29 (83%) and C in 6 (17%) patients, while the mean Tegner score was 6 (range 4-8). The mean Lysholm score was 90.83 (range 81-95) and mean SF-12 physical and mental scores were 54.1 (range 45-60) and 51.0 (range 39-62) respectively. In 2 patients, a secondary operation was performed. CONCLUSIONS Early, one stage reconstruction with DIS can achieve good functional results and patient satisfaction with overall restoration of sports and working capacity without graft requirements.