Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization,Biomechanical and Biocompatibility Characterization Using New Approaches

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients’ quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients’ quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.     

Speckle interferometry measurements of the conductor displacementsin the CERN-LHC main dipole

Magnetic field quality in superconducting magnets strongly depends on conductor position in operational conditions. Simulations based on finite-element models (FEM) provide the field of stresses and displacements inside the magnet. Due to the complex mechanical behavior of the coil and to the different materials composing the magnet, it is not trivial to build a reliable mechanical model. We present an experimental method based on optical measurements to validate the accuracy of the FEM in evaluating differential displacements at room temperature. A short sample of dipole coils is loaded through a small press and speckle interferometry measurements detect differential displacements with an accuracy of 1.5 μm. Comparison with the numerical results allows the testing of the most critical features of the model, i.e., a pressure-dependent coil elasticity and the interfaces between different materials. A good agreement between measurements and deformed geometry foreseen by the FEM is found     

Correlations between field quality and geometry of components in the collared coils of the LHC main dipoles

The Large Hadron Collider (LHC) (1995), a proton-proton superconducting accelerator, will consist of about 8400 superconducting magnet units, all operating in superfluid helium at a temperature of 1.9 K. The design of the superconducting main dipole magnets for the LHC is guided by the requirement of an extremely high field quality in the magnet aperture which is mainly defined by the layout of the superconducting coil and the position of the conductors. In order to avoid conductor movements within the magnet cross-section, the superconducting coils are held in place by surrounding stainless steel collars. In this paper, we review the dependence of field harmonics in the LHC main dipoles on dimensions of the hardware components of the collared coils. An analysis of the dimensional measurements of these components which are used in the collared coils produced so far is given. Sensitivity tables which are worked out through a coupled magneto-static model give the variation of the multipoles on collars, copper wedge dimensions and cable geometry. A Monte Carlo method is used to simulate the effects of possible errors on the multipoles.     

Effect of altitude on body composition during mountaineering expeditions: interrelationships with changes in dietary habits

The concepts involved in the process of managing change successfully in respect of the management of human resources are as complex as they are contentious, with arguments and counter-arguments espoused weekly in the seemingly ever-growing plethora of literature available. The following paper attempts to present a critical analysis of the management of change from the perspective of the human resource and to debate the relative merits pertaining to the imperatives of organizational design and culture, in conjunction with a plea to recognize and respect peoples' needs and feelings, in relation to the impact of internal market reform upon management practice within the context of the contemporary National Health Service (NHS). The paper is predicated upon the dual beliefs that people and organizations are dynamic entities being located both temporally and socially, and that any constructed criterions of success must, therefore, be evaluated not only in terms of the specific individual and/or organizational parameters but also in terms of the relative cultural, moral, philosphical and political ethos, and that as the human race largely survives and operates via organization, which in itself has to be managed, controlled and developed, managers are, therefore, a vital element of any successful organization.     

Efficacy and tolerability of etodolac in aged patients affected by degenerative joint disease (osteoarthritis) in its active phase

Three-hundred-and-fifteen patients, aged 60 or more years, affected by degenerative joint disease (DJD) in the active stage, the majority with concomitant pathological conditions of various organs and systems and undergoing various combined drug treatments, were treated with 300 mg b.i.d. etodolac in order to assay its efficacy and safety profile in an aged population more exposed to the occurrence of adverse events. In a subset of these patients, the impact of etodolac treatment on cognitive function and mood was studied. All clinical assessments revealed highly significant improvement after etodolac treatment. Significant improvement was found also for what concerns mood, whereas only the less aged patients showed improvement in cognitive abilities after treatment with etodolac. Only 30 patients (9.5%) showed side-effects, resulting in suspension of treatment in 10 cases (3.17%). In all cases, adverse reactions subsided with no consequences. Laboratory tests performed at the end of the study yielded mean values comprised within the normal range and were not statistically different from the same examinations performed before starting treatment. Occult blood in stool turned positive after treatment with etodolac only in six patients (2%). In conclusion, etodolac proved to be effective and well-tolerated in the treatment of risk-aged patients with active DJD.     

Production follow-up of the LHC main dipoles through magnetic measurements at room temperature

In this paper, we review the tools used for controlling the production of the LHC main dipoles through warm magnetic measurements. For the collared coil measurements, control limits are based on the statistics relative to the pre-series production. For the cold mass, the difference between collared coil and cold mass is considered, allowing a very stringent test. In both cases, measurements are split in straight part average, variations and coil ends contributions. Two different alarm levels exist in case the measured field is out of limits. The analysis can be carried out at the manufacturer and allows detection of anomalies in the measured magnetic field. These can be either due to wrong measurements or caused by assembly defects. Techniques used to work out information on the magnet assembly from the field harmonics are outlined. We summarize the experience gathered on about 180 collared coils and 120 cold masses, pointing out the bad cases and investigating the reliability of the measurements.     

Chondrocalcinosis is a feature of Gitelman's variant of Bartter's syndrome. A new look at the hypomagnesemia associated with calcium pyrophosphate dihydrate crystal deposition disease

The occurrence of chondrocalcinosis in patients with Bartter's syndrome has been reported as a typical example of hypomagnesemia-associated calcium pyrophosphate dihydrate crystal (CPPD) deposition disease. However, hypomagnesemia is a feature of Gitelman's variant of Bartter's syndrome, whereas serum magnesium levels are normal in Bartter's syndrome strictly speaking. We managed four patients with chondrocalcinosis and hypomagnesemia who met criteria for Gitelman's disease, including hypomagnesemia, hypokalemia with normal or high urinary potassium excretion, hypocalciuria, and normal blood pressure. Based on our experience with these patients, we argue that many cases of chondrocalcinosis and hypomagnesemia ascribed in previously published articles to Bartter's syndrome were due to Gitelman's syndrome.