Quantification of bone strength by intraoperative torque measurement: a technical note

Introduction: Bone strength describes the resistance of bone against mechanical failure. Bone strength depends on both the amount of bone and the bone's quality, and the bone strength may be looked upon as a relevant parameter to judge an osteosynthesis' stability. Information about bone strength was barely available intraoperatively in the past. The previous work of our group reported on development and laboratory evaluation of mechanical torque measurement as a method for the intraoperative quantification of bone strength. With the clinical series presented here we intend to verify that the im gesamten Text DensiProbe™ instrumentation for intraoperative torque measurement and the related measurement method are eligible for intraoperative use based on the following criteria: application of the method may not create complications, the measurement can be performed by the surgeon himself and may only cause a limited increase in the procedure time. Patients and methods: From December 2006 until May 2007 ten patients with a pertrochanteric femoral fracture or a lateral femoral neck fracture eligible for stabilization with DHS® were included in the study after having received informed consent. Any medication and comorbidity that might have influenced bone quality or bone mineral density (BMD) in these patients was documented. Bone strength was intraoperatively measured with DensiProbe®. Complications that were obviously related with torque measurement were documented as well as any deviation from the suggested procedure; 6 and 12 weeks postoperative follow-up included clinical and radiological examination. The time required for torque measurement, the overall operating time and the number of persons present in the operating room were protocolled. BMD values of the contralateral femoral neck were postoperatively assessed by dual energy X-ray absorptiometry (DEXA) and compared to intraoperative peak torque values measured by DensiProbe®. Results: No major complication was observed during intraoperative application of DensiProbe®by trained surgeons. The unintended extraction of the guide wire together with the torque measurement probe was reported only once and is looked upon as a minor complication. Fracture healing was uneventful in all patients. The mean time for torque measurement was 2.35±0.9min accounting for 2.2±1.1% of total surgery time. The presence of an additional person was not required to perform torque measurement but to protocol the data. There was a tendency towards correlation between BMD values of the femoral neck and intraoperative peak torque values. Discussion: The data presented clearly indicate that the DensiProbe® instrumentation and measurement principle are eligible for routine intraoperative use by trained surgeons. Interpretation of possible correlations between BMD values measured by means of DEXA and the Peak Torque values assessed by DensiProbe® has to be considered very carefully, because BMD and Peak Torque analyse bone at a different scale. Only within the framework of a multicenter study it will be possible to include a sufficient number of patients for calculation of the methods' predictive value towards implant failure and to verify acceptance of the method by the surgeon

Three-dimensional imaging of the larynx for pre-operative planning of laryngeal framework surgery

Modern laryngeal framework surgery (LFS) requires an exact understanding of the laryngeal biomechanics and precise pre-operative planning, for which bi-planar imaging is not sufficient. The aim of the study was to test whether MIMICS®, a commercially available software package for three-dimensional (3D) rendering of high-resolution computerised tomography (HRCT), is suitable for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning. We examined four cadaver larynx and one patient larynx. In the five larynges, all relevant structures and landmarks could be 3D visualised. Superimposing of two HRCT scans shows that when the arytenoids move from ‘respiration' to ‘phonation', they perform a rotating, translating and tilting motion. Moreover, we could demonstrate that the vocal fold elongates by 7% with cricothyroid approximation. We conclude that MIMCS® is well suited for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning of LFS procedure

A probabilistic trust model for GnuPG

Trust networks are possible solutions for the key authenticity problem in a decentralized public-key infrastructure. A particular trust model, the so-called Web of Trust, has been proposed for and is implemented in the popular e-mail encryption software PGP and its open source derivatives like GnuPG. In this paper, we investigate the drawbacks and weaknesses of the current PGP and GnuPG trust model, and we propose a new approach to handle trust and key validity in a more sophisticated way. A prototype of our solution has been implemented and tested with the current GnuPG release. 1

X-ray Structures and Feasibility Assessment of CLK2 Inhibitors for Phelan–McDermid Syndrome

CLK2 inhibition has been proposed as a potential mechanism to improve autism and neuronal functions in Phelan–McDermid syndrome (PMDS). Herein, the discovery of a very potent indazole CLK inhibitor series and the CLK2 X-ray structure of the most potent analogue are reported. This new indazole series was identified through a biochemical CLK2 Caliper assay screen with 30k compounds selected by an in silico approach. Novel high-resolution X-ray structures of all CLKs, including the first CLK4 X-ray structure, bound to known CLK2 inhibitor tool compounds (e.g., TG003, CX-4945), are also shown and yield insight into inhibitor selectivity in the CLK family. The efficacy of the new CLK2 inhibitors from the indazole series was demonstrated in the mouse brain slice assay, and potential safety concerns were investigated. Genotoxicity findings in the human lymphocyte micronucleus test (MNT) assay are shown by using two structurally different CLK inhibitors to reveal a major concern for pan-CLK inhibition in PMDS

Three-dimensional imaging of the larynx for pre-operative planning of laryngeal framework surgery

Modern laryngeal framework surgery (LFS) requires an exact understanding of the laryngeal biomechanics and precise pre-operative planning, for which bi-planar imaging is not sufficient. The aim of the study was to test whether MIMICS, a commercially available software package for three-dimensional (3D) rendering of high-resolution computerised tomography (HRCT), is suitable for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning. We examined four cadaver larynx and one patient larynx. In the five larynges, all relevant structures and landmarks could be 3D visualised. Superimposing of two HRCT scans shows that when the arytenoids move from 'respiration' to 'phonation', they perform a rotating, translating and tilting motion. Moreover, we could demonstrate that the vocal fold elongates by 7% with cricothyroid approximation. We conclude that MIMCS is well suited for 3D imaging of the larynx, analysis of laryngeal biomechanics and pre-operative planning of LFS procedures

PAX8 and MECOM are interaction partners driving Ovarian Carcinogenesis

The transcription factor PAX8 is critical for the development of the thyroid and urogenital system. Comprehensive genomic screens furthermore indicate an additional oncogenic role for PAX8 in renal and ovarian carcinogenesis. While a plethora of PAX8-regulated genes in different contexts have been proposed, we still lack a mechanistic understanding of how PAX8 engages molecular complexes to drive disease-relevant oncogenic transcriptional programs. Here we show that protein isoforms originating from the MECOM locus form a complex with PAX8. This includes PRDM3 (also called MDS1-EVI1) for which we map its interaction with PAX8 in vitro and in vivo. We show that PAX8 binds a large number of genomic sites and forms transcriptional hubs. At a subset of these, PAX8 together with PRDM3 regulate a specific gene expression module involved in adhesion and extracellular matrix. This gene module correlates with PAX8 and MECOM expression in large scale profiling of cell lines, PTXs and clinical cases and stratifies gynecological cancer cases with worse prognosis. PRDM3 is amplified in Ovarian Cancers and we show that the MECOM locus and PAX8 sustain in-vivo ovarian cancer growth, further supporting that the identified function of the MECOM locus underlies PAX8-driven oncogenic functions in ovarian cancer