No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. TRIAL REGISTRATION NUMBER: N/A.

Load-Sharing and Kinematics of the Human Cervical Spine Under Multi-Axial Transverse Shear Loading: Combined Experimental and Computational Investigation.

The cervical spine experiences shear forces during everyday activities and injurious events yet there is a paucity of biomechanical data characterizing the cervical spine under shear loading. This study aimed to (1) characterize load transmission paths and kinematics of the subaxial cervical spine under shear loading, and (2) assess a contemporary finite element cervical spine model using this data. Subaxial functional spinal units (FSUs) were subjected to anterior, posterior, and lateral shear forces (200 N) applied with and without superimposed axial compression preload (200 N) while monitoring spine kinematics. Load transmission paths were identified using strain gauges on the anterior vertebral body and lateral masses and a disc pressure sensor. Experimental conditions were simulated with cervical spine finite element model FSUs (GHBMC M50 version 5.0). The mean kinematics, vertebral strains, and disc pressures were compared to experimental results. The shear force-displacement response typically demonstrated a toe region followed by a linear response, with higher stiffness in anterior shear relative to lateral and posterior shear. Compressive axial preload decreased posterior and lateral shear stiffness and increased initial anterior shear stiffness. Load transmission patterns and kinematics suggest the facet joints play a key role in limiting anterior shear while the disc governs motion in posterior shear. The main cervical spine shear responses and trends are faithfully predicted by the GHBMC cervical spine model. These basic cervical spine biomechanics and the computational model can provide insight into mechanisms for facet dislocation in high severity impacts, and tissue distraction in low severity impacts.

[Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes. German version]. / Scannende laseroptische Tomographie in einem neuropathischen Mausmodell : Visualisierung von strukturellen Veränderungen.

BACKGROUND: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting. The Cav1.3-/- mice have already been extensively characterized and show structural changes in the inner ear. Therefore, they were used in this study as a model to investigate whether SLOT can detect structural differences in the murine cochlea. MATERIALS AND METHODS: Whole undissected cochleae from Cav1.3-/- and wildtype mice of various postnatal stages were immunostained and analyzed by SLOT. The results were compared to cochlea preparations that were immunostained and analyzed by fluorescence microscopy. In addition, cochlea preparations were stained with osmium tetraoxide. RESULTS: Visualization by SLOT showed that the staining of nerve fibers at P27 in Cav1.3-/- mice was almost absent compared to wildtype mice and earlier timepoints (P9). The analysis of cochlea preparations confirmed a reduction of the radial nerve fibers. In addition, a significantly reduced number of ribbon synapses per inner hair cell (IHC) at P20 and P27 in the apical part of the cochlea of Cav1.3-/- mice was detected. CONCLUSION: The visualization of whole non-dissected cochleae by SLOT is a suitable tool for the analysis of gross phenotypic changes, as demonstrated by means of the Cav1.3-/- mouse model. For the analysis of finer structures of the cochlea, however, further methods must be used.

Scanning laser optical tomography in a neuropathic mouse model : Visualization of structural changes.

BACKGROUND: In the field of hearing research a variety of imaging techniques are available to study molecular and cellular structures of the cochlea. Most of them are based on decalcifying, embedding, and cutting of the cochlea. By means of scanning laser optical tomography (SLOT), the complete cochlea can be visualized without cutting. The Cav1.3-/- mice have already been extensively characterized and show structural changes in the inner ear. Therefore, they were used in this study as a model to investigate whether SLOT can detect structural differences in the murine cochlea. MATERIALS AND METHODS: Whole undissected cochleae from Cav1.3-/- and wild-type mice of various postnatal stages were immunostained and analyzed by SLOT. The results were compared to cochlea preparations that were immunostained and analyzed by fluorescence microscopy. In addition, cochlea preparations were stained with osmium tetraoxide. RESULTS: Visualization by SLOT showed that the staining of nerve fibers at P27 in Cav1.3-/- mice was almost absent compared to wild-type mice and earlier timepoints (P9). The analysis of cochlea preparations confirmed a reduction of the radial nerve fibers. In addition, a significantly reduced number of ribbon synapses per inner hair cell (IHC) at P20 and P27 in the apical part of the cochlea of Cav1.3-/- mice was detected. CONCLUSION: The visualization of whole non-dissected cochleae by SLOT is a suitable tool for the analysis of gross phenotypic changes, as demonstrated by means of the Cav1.3-/- mouse model. For the analysis of finer structures of the cochlea, however, further methods must be used.

A rapid review of needs assessment tools for post-treatment cancer survivors.

Relevant, comprehensive and psychometrically rigorous needs assessment tools are needed to ensure appropriate care is delivered to cancer survivors who have completed treatment. The aim of this rapid review was to identify and describe needs assessment tools that are used in cancer survivors post-treatment, assess their psychometric properties and describe their use in clinical care. The electronic databases Medline, Cochrane Library, CINAHL and PsycINFO were searched. Six studies were identified that described five needs assessment tools used in cancer survivors post-treatment. None of these tools covered all domains of unmet need nor demonstrated adequate evidence of all recommended criteria of validity and reliability. Few had been evaluated for use in a clinical environment. Out of the five tools, the Survivor Unmet Needs Survey (SUNS) showed the strongest psychometric properties. There is little empirical evidence available to guide recommendations on the most appropriate process of conducting needs assessment with cancer survivors once they have completed treatment.

Development and evaluation of an online educational resource about cancer survivorship for cancer nurses: a mixed-methods sequential study.

Cancer survivorship is recognised globally as a key issue. In spite of the key role played by nurses in survivorship care, there is an identified gap in nurse's knowledge in this area. This study reports on the development and evaluation of an educational resource for nurses working with people affected by cancer. The resource was designed using adult learning principles and includes a variety of learning materials and point of care resources. A mixed-methods sequential exploratory design was used to undertake an evaluation of the programme. This included the use of online surveys and semi-structured interviews with pilot participants. A total of 21 participants completed an online survey and 11 participants completed a telephone interview. Overall, the participants found the Cancer Survivorship resource to be engaging, practical and intuitive. A major theme emerging from the survey and interview data was that the resource was applicable to practice and useful in developing survivorship care plans. Respondents requested additional information be included on the role of various health professionals working in survivorship as well as guidelines on when to make referrals. This study provides evidence that the Cancer Survivorship tool may be a promising vehicle for delivering evidence-based education on survivorship care.

[12 years of Computer-Aided Surgery around the Head : Developments in surgical planning and simulation from a Bern perspective]. / 12 Jahre Computer-Aided Surgery around the Head : Entwicklungen in der chirurgischen Planung und Simulation aus Berner Perspektive.

Over the past years, the multidisciplinary character of the international Computer-Aided Surgery around the Head (CAS-H) symposium has advanced many medical technologies, which were often adopted by industry. In Bern, the synergetic effects of the CAS-H symposium have enabled many experiences and developments in the area of computer-aided surgery. Planning and simulation methods in the areas of craniomaxillofacial surgery and otorhinolaryngology were developed and tested in clinical settings. In the future, further CAS-H symposia should follow, in order to promote the possibilities and applications of computer-assisted surgery around the head.

Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice.

To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.

[Navigation and robotics of the lateral skull base]. / Navigation und Robotik an der Otobasis.

Computer-aided microscopic surgery of the lateral skull base is a rare intervention in daily practice. It is often a delicate and difficult minimally invasive intervention, since orientation between the petrous bone and the petrous bone apex is often challenging. In the case of aural atresia or tumors the normal anatomical landmarks are often absent, making orientation more difficult. Navigation support, together with imaging techniques such as CT, MR and angiography, enable the surgeon in such cases to perform the operation more accurately and, in some cases, also in a shorter time. However, there are no internationally standardised indications for navigated surgery on the lateral skull base. Miniaturised robotic systems are still in the initial validation phase.

[Computer-aided surgery of the paranasal sinuses and the anterior skull base]. / Computerassistierte Chirurgie der Nasennebenhöhlen und der vorderen Schädelbasis.

Endoscopic or microscopic surgery for chronic rhinosinusitis with or without nasal polyps is a routine intervention in daily practice. It is often a delicate and difficult minimally invasive intervention in a narrow space, with a tunnel view of 4 mm in the case of endoscopy and frequent bleeding in chronically inflamed tissue. Therefore, orientation in such a "labyrinth" is often difficult. In the case of polyp recurrence or tumors, the normal anatomical landmarks are often missing, which renders orientation even more difficult. In such cases, computer-aided navigation together with images such as those from computed tomography or magnetic resonance imaging can support the surgeon to make the operation more accurate and, in some cases, faster. Computer-aided surgery also has great potential for education.

Superficial femoral artery recanalization with self-expanding nitinol stents: long-term follow-up results.

PURPOSE: Since long-term patency and device integrity of nitinol stents in SFA lesions are not well studied, we examined clinical outcome, patency and device integrity after stenting long lesions using a standardized implantation technique. METHODS: Between 2001 and 2006, 59 patients (74 lesions) were treated with the same nitinol self-expandable stent (Zilver, Cook, USA) and technique for SFA recanalization. Clinical charts and imaging were retrospectively reviewed for patency (primary and assisted-primary), and device integrity. RESULTS: Patients were 74.5 (10.9) years old (range 49 to 93), 64% male, 42% diabetic, 62% hypertensive and 67% current or former smokers. Lesions were 23% TASC B, 16% TASC C, or 61% TASC D. Mean recanalization length was 19 cm (range 3 to 53). Mean number of stents per patient was 2.8 (total 210). Mean follow-up time was 2.4 years (range 3 days to 4.8 years). Kaplan-Meier estimates for primary patency rates were 90%, 78%, 74%, 69%, and 69% at 1, 2, 3, 4 and 4.8 years, respectively. Ten restenoses at a mean of 500 (388) days (1-1251 days) were successfully recanalized. The assisted primary patency rates were 96%, 90%, 90%, 90% and 90% at 1, 2, 3, 4 and 5 years, respectively. Six complete occlusions could not be reverted by a second recanalization procedure, and were treated by surgical bypass (1 case), amputation (3 cases), or medical management (2 cases). One (1.04%) Class II stent fracture was noted. CONCLUSIONS: SFA recanalization with a standardized implantation technique and nitinol stents provides good long-term primary and assisted-primary patency.

Accuracy considerations in navigated cup placement for total hip arthroplasty.

Computer assisted orthopaedic surgery (CAOS) technology has recently been introduced to overcome problems resulting from acetabular component malpositioning in total hip arthroplasty. Available navigation modules can conceptually be categorized as computer tomography (CT) based, fluoroscopy based, or image-free. The current study presents a comprehensive accuracy analysis on the computer assisted placement accuracy of acetabular cups. It combines analyses using mathematical approaches, in vitro testing environments, and an in vivo clinical trial. A hybrid navigation approach combining image-free with fluoroscopic technology was chosen as the best compromise to CT-based systems. It introduces pointer-based digitization for easily assessable points and bi-planar fluoroscopy for deep-seated landmarks. From the in vitro data maximum deviations were found to be 3.6 degrees for inclination and 3.8 degrees for anteversion relative to a pre-defined test position. The maximum difference between intraoperatively calculated cup inclination and anteversion with the postoperatively measured position was 4 degrees and 5 degrees, respectively. These data coincide with worst cases scenario predictions applying a statistical simulation model. The proper use of navigation technology can reduce variability of cup placement well within the surgical safe zone. Surgeons have to concentrate on a variety of error sources during the procedure, which may explain the reported strong learning curves for CAOS technologies.

A CT-free, intra-operative planning and navigation system for minimally invasive anterior spinal surgery - an accuracy study.

OBJECTIVE: A comprehensive study was performed to evaluate the accuracy of a newly developed CT-free, intra-operative planning and navigation system for anterior spine surgery. MATERIALS AND METHODS: Instruments and an image intensifier were tracked using the SurgiGATE navigation system. A laboratory study was performed on 27 plastic vertebrae. Fiducial markers were implanted in the vertebrae for accuracy evaluation purposes, and a dynamic reference base was placed on the vertebrae to establish a patient coordinate system (P-COS). Two fluoroscopic images were used for intra-operative planning. The graft bed plan was recorded in P-COS, followed by surgical formation of the graft bed, which was visualized. To evaluate the accuracy, the vertebrae were scanned with CT, and the markers were used to calculate an accurate paired-point registered transformation between the CT coordinate system and P-COS. RESULTS: Using the new SPO module, accurate planning and navigation of a resection of the vertebral body is possible using two fluoroscopic images. The overall mean error between the planned resection volume and the actual resection was 0.98 mm. In addition, the module can serve as an educational tool for training spine surgeons. CONCLUSIONS: The new fluoroscopy-based system can be used safely for accurate performance of anterior resection during spondylodesis. New methods for safe and accurate registration during anterior spine surgery need to be developed.

Computer-assisted, fluoroscopy-based ventral spondylodesis of thoracolumbar fractures.

OBJECTIVE: To design and evaluate a novel computer-assisted, fluoroscopy-based planning and navigation system for minimally invasive ventral spondylodesis of thoracolumbar fractures. MATERIALS AND METHODS: Instruments and an image intensifier are tracked with the SurgiGATE navigation system (Praxim-Medivision). Two fluoroscopic images, one acquired from anterior-posterior (AP) direction and the other from lateral-medial (LM) direction, are used for the complete procedure of planning and navigation. Both of them are calibrated with a custom-made software to recover their projection geometry and to co-register them to a common patient reference coordinate system, which is established by attaching an opto-electronically trackable dynamic reference base (DRB) on the operated vertebra. A bi-planar landmark reconstruction method is used to acquire deep-seated anatomical landmarks such that an intraoperative planning of graft bed can be interactively done. Finally, surgical actions such as the placement of the stabilization devices and the formation of the graft bed using a custom-made chisel are visualized to the surgeon by superimposing virtual instrument representations onto the acquired images. The distance between the instrument tip and each wall of the planned graft bed are calculated on the fly and presented to the surgeon so that the surgeon could formalize the graft bed exactly according to his/her plan. RESULTS: Laboratory studies on phantom and on 27 plastic vertebras demonstrate the high precision of the proposed navigation system. Compared with CT-based measurement, a mean error of 1.0 mm with a standard deviation of 0.1 mm was found. CONCLUSIONS: The proposed computer assisted, fluoroscopy-based planning and navigation system promises to increase the accuracy and reliability of minimally invasive ventral spondylodesis of thoracolumbar fractures.

Removal of adenosine decreases the responsiveness of muscle glucose transport to insulin and contractions.

Adenosine in the extracellular space modulates stimulated glucose transport in striated muscle. In the heart and in adipocytes, adenosine potentiates insulin-stimulated glucose transport. There is controversy regarding the effect of adenosine in skeletal muscle, with reports of both an inhibitory effect and no effect, on insulin-stimulated glucose transport. We found that, in rat epitrochlearis and soleus muscles, removing adenosine with adenosine deaminase or blocking its action with the adenosine receptor blocker CPDPX markedly reduces the responsiveness of glucose transport to stimulation by 1) insulin alone, 2) contractions alone, and 3) insulin and contractions in combination. Measurement of the increase in GLUT4 at the cell surface in response to a maximally effective insulin stimulus in the epitrochlearis muscle, using the exofacial label ATB-[3H]BMPA, showed that adenosine deaminase treatment markedly reduces cell-surface GLUT4 labeling. The reduction in cell-surface GLUT4 labeling was similar in magnitude to the decrease in maximally insulin-stimulated glucose transport activity in adenosine deaminase-treated muscles. These results show that adenosine potentiates insulin- and contraction-stimulated glucose transport in skeletal muscle by enhancing the increase in GLUT4 at the cell surface and raise the possibility that decreased adenosine production or action could play a causative role in insulin resistance.

Hyperglycemia activates glucose transport in rat skeletal muscle via a Ca(2+)-dependent mechanism.

We investigated the acute effect of hyperglycemia on 3-O-methylglucose transport in isolated rat epitrochlearis muscles. High levels of glucose (20 mmol/l) induced an approximately twofold increase in the rate of glucose transport when compared with muscles exposed to a low level of glucose (8 mmol/l) (P < 0.001). The hyperglycemic effect was additive to the effects of both insulin and exercise on the glucose transport rates. Dantrolene (25 mumol/l), a potent inhibitor of Ca2+ release from the sarcoplasmic reticulum, blocked the ability of hyperglycemia to increase glucose transport by 73% (P < 0.01). Although dantrolene had no effect on the non-insulin-stimulated or the insulin-stimulated glucose transport rates during normoglycemic conditions, the effect of exercise was completely blocked in the presence of dantrolene (P < 0.01). Inhibition of phosphatidylinositol (PI) 3-kinase by wortmannin (500 nmol/l) had no effect on the activation of glucose transport by hyperglycemia, whereas the insulin-stimulated glucose transport was completely abolished (P < 0.001). These findings suggest that hyperglycemia activates glucose transport by a Ca(2+)-dependent activation of glucose transport does not involve the activation of PI 3-kinase and is separate from the mass-action effect of glucose on glucose transport.

The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle.

In many patients with human immunodeficiency virus (HIV) treated with HIV protease inhibitors, a complication develops that resembles abdominal obesity syndrome, with insulin resistance and glucose intolerance that, in some cases, progresses to diabetes. In this study, we tested the hypothesis that indinavir, an HIV-protease inhibitor, directly induces insulin resistance of glucose transport in skeletal muscle. Rat epitrochlearis muscles were incubated with a maximally effective insulin concentration (12 nmol/l) and 0, 1, 5, 20, or 40 micromol/l indinavir for 4 h. In control muscles, insulin increased 3-O-[(3)H]methyl-D-glucose (3MG) transport from 0.15 +/- 0.03 to 1.10 +/- 0.05 micromol. ml(-)(1). 10 min(-)(1). Incubation of muscles with 5 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 40%, whereas 20 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 58%. Indinavir induced a similar reduction in maximally insulin-stimulated 3MG transport in the soleus muscle. The increase in glucose transport activity induced by stimulating epitrochlearis muscles to contract was also markedly reduced by indinavir. The insulin-stimulated increase in cell-surface GLUT4, assessed using the 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-[2-(3)H] (D-mannose-4-yloxy)-2-propylamine exofacial photolabeling technique, was reduced by approximately 70% in the presence of 20 micromol/l indinavir. Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir. These results provide evidence that indinavir inhibits the translocation or intrinsic activity of GLUT4 rather than insulin signaling.

Effect of insulin on GLUT4 cell surface content and turnover rate in human skeletal muscle as measured by the exofacial bis-mannose photolabeling technique.

Insulin-stimulated glucose transport across the skeletal muscle cell membrane is a major regulatory step in postprandial glucose disposal. To estimate the total molar concentration of GLUT4 as well as the turnover rate of GLUT4 in human vastus lateralis muscles at the cell surface in the basal state and after insulin exposure, we have applied the sensitive exofacial bis-mannose photolabeling technique on in vitro incubated human skeletal muscle strips from healthy subjects. In addition, we have measured 3-O-methylglucose transport in other muscle strips prepared from the same surgically removed human skeletal muscle biopsies to compare glucose transport with cell surface level of GLUT4. Maximal in vitro insulin stimulation (2,400 pmol/l) resulted in a twofold increase compared with basal in both surface GLUT4 content (0.38 +/- 0.05 vs. 0.19 +/- 0.03 pmol/g wet muscle wt, P < 0.005) and 3-O-methylglucose transport (1.24 +/- 0.13 vs. 0.63 +/- 0.08 pmol x ml(-1) x h(-1), P < 0.005). The insulin-induced increment in 3-O-methylglucose transport was strongly correlated with the insulin-induced increase in cell surface GLUT4 content (r2 = 0.91; P < 0.005). The calculated turnover rate of human skeletal muscle GLUT4 amounted to approximately 8 x 10(4) min(-1) at 35 degrees C and was unaffected by insulin. In conclusion, maximal in vitro insulin stimulation of vastus lateralis muscle strips from healthy subjects resulted in a twofold rise in glucose transport as well as in cell surface content, whereas the turnover rate of GLUT4 was unaffected by insulin under the chosen experimental conditions.

Short-term exposure to tumor necrosis factor-alpha does not affect insulin-stimulated glucose uptake in skeletal muscle.

It has been hypothesized that increased production of tumor necrosis factor-alpha (TNF-alpha) plays a role in causing the insulin resistance associated with obesity. Obesity with insulin resistance is associated with increased production of TNF-alpha by fat cells. Exposure of 3T3-L1 adipocytes to TNF-alpha for 3-4 days makes them insulin resistant. TNF-alpha has also been reported to rapidly (15-60 min) cause insulin resistance, with a decrease in insulin-stimulated tyrosine phosphorylation, in a number of cultured cell lines. Because skeletal muscle is the major tissue responsible for insulin-stimulated glucose disposal, we performed the present study to determine if acute exposure to TNF-alpha causes insulin resistance in muscle. We found that exposure of soleus muscles to 6 nmol/l TNF-alpha for 45 min in vitro had no inhibitory effect on insulin-stimulated tyrosine phosphorylation of the insulin receptor or insulin receptor substrate 1 (IRS-1) or on phosphatidylinositol 3-kinase association with IRS-1. Incubation of epitrochlearis and soleus muscles with 6 nmol/l TNF-alpha for 45 min or 4 h had no effect on insulin-stimulated 2-deoxyglucose (2-DG) uptake. Treatment of epitrochlearis muscles with 2 nmol/l TNF-alpha for 8 h also had no effect on insulin-stimulated 2-DG uptake. We conclude that in contrast to Fao hepatoma cells and 3T3-L1 fibroblasts, skeletal muscle does not become insulin resistant in response to short-term exposure to TNF-alpha.

New orthopaedic implant management tool for computer-assisted planning, navigation, and simulation: from implant CAD files to a standardized XML-based implant database.

Computer-Assisted Orthopaedic Surgery (CAOS) has made much progress over the last 10 years. Navigation systems have been recognized as important tools that help surgeons, and various such systems have been developed. A disadvantage of these systems is that they use non-standard formalisms and techniques. As a result, there are no standard concepts for implant and tool management or data formats to store information for use in 3D planning and navigation. We addressed these limitations and developed a practical and generic solution that offers benefits for surgeons, implant manufacturers, and CAS application developers. We developed a virtual implant database containing geometrical as well as calibration information for orthopedic implants and instruments, with a focus on trauma. This database has been successfully tested for various applications in the client/server mode. The implant information is not static, however, because manufacturers periodically revise their implants, resulting in the deletion of some implants and the introduction of new ones. Tracking these continuous changes and keeping CAS systems up to date is a tedious task if done manually. This leads to additional costs for system development, and some errors are inevitably generated due to the huge amount of information that has to be processed. To ease management with respect to implant life cycle, we developed a tool to assist end-users (surgeons, hospitals, CAS system providers, and implant manufacturers) in managing their implants. Our system can be used for pre-operative planning and intra-operative navigation, and also for any surgical simulation involving orthopedic implants. Currently, this tool allows addition of new implants, modification of existing ones, deletion of obsolete implants, export of a given implant, and also creation of backups. Our implant management system has been successfully tested in the laboratory with very promising results. It makes it possible to fill the current gap that exists between the CAS system and implant manufacturers, hospitals, and surgeons.