Phase shifting speckle interferometry for determination of strain and Young's modulus of mineralized biological materials: a study of tooth dentin compression in water

Mineralized biological materials have complex hierarchical graded structures. It is therefore difficult to understand the relations between their structure and mechanical properties. We report the use of electronic speckle pattern-correlation interferometry (ESPI) combined with a mechanical compression apparatus to measure the strain and Young's modulus of root dentin compressed under water. We describe the optomechanical instrumentation, experimental techniques and procedures needed to measure cubes as small as 1 x 1 x 2 mm. Calibration of the method is performed using aluminum, which shows that the measurements are accurate within 3% of the compression modulus reported for standard aluminum 6061. Our results reveal that the compression moduli of root dentin from the buccal and lingual sides of the root are quite different from the moduli of the interproximal sides. Root dentin from interproximal locations is found to have an average modulus of 21.3 GPa, which is about 40% stiffer than root dentin from the buccal and lingual locations, found to have a modulus of 15.0 GPa. Our approach can be used to map deformations on irregular surfaces, and measure strain on wet samples of varying sizes. This can be extended to the study of other biological materials including bone and synthetic biomaterials.     

Molecular mechanism of a thumb domain hepatitis C virus nonnucleoside RNA-dependent RNA polymerase inhibitor

A new pyranoindole class of small-molecule inhibitors was studied to understand viral resistance and elucidate the mechanism of inhibition in hepatitis C virus (HCV) replication. HCV replicon variants less susceptible to inhibition by the pyranoindoles were selected in Huh-7 hepatoma cells. Variant replicons contained clusters of mutations in the NS5B polymerase gene corresponding to the drug-binding pocket on the surface of the thumb domain identified by X-ray crystallography. An additional cluster of mutations present in part of a unique beta-hairpin loop was also identified. The mutations were characterized by using recombinant replicon variants engineered with the corresponding amino acid substitutions. A single mutation (L419M or M423V), located at the pyranoindole-binding site, resulted in an 8- to 10-fold more resistant replicon, while a combination mutant (T19P, M71V, A338V, M423V, A442T) showed a 17-fold increase in drug resistance. The results of a competition experiment with purified NS5B enzyme with GTP showed that the inhibitory activity of the pyranoindole inhibitor was not affected by GTP at concentrations up to 250 microM. Following de novo initiation, the presence of a pyranoindole inhibitor resulted in the accumulation of a five-nucleotide oligomer, with a concomitant decrease in higher-molecular-weight products. The results of these studies have confirmed that pyranoindoles target the NS5B polymerase through interactions at the thumb domain. This inhibition is independent of GTP concentrations and is likely mediated by an allosteric blockade introduced by the inhibitor during the transition to RNA elongation after the formation of an initiation complex.     

Anti-tumor immunoglobulin M increases lung metastasis in an experimental model of malignant melanoma

Cancer metastasis involves distinct steps that depend on complicated tumor–host interactions. The hematogenous dissemination of tumor cells may be facilitated by factors that promote the arrest and adherence of cancer cells in capillaries. We examined whether anti-tumor monoclonal immunoglobulin M (IgM) antibodies promoted the hematogenous dissemination of B16 melanoma cells in syngeneic mice. IgM monoclonal antibodies were generated that selectively bind to B16 melanoma cells as compared to syngeneic fibroblasts, lymphocytes or Lewis lung carcinoma cells. Incubation of B16-BL6 or B16-F0 melanoma cells with these IgM anti-tumor antibodies significantly increased the number of lung colonies as compared with control antibodies. Moreover, intraperitoneal injection of specific antibody also significantly increased lung colonization. All anti-tumor antibodies promoted the aggregation of B16 melanoma cells. A chemically generated immunoglobulin G (IgG)-like fragment of an anti-tumor IgM antibody displayed greatly reduced tumor aggregation and, in contrast to intact IgM, did not significantly increase lung colonization of B16 melanoma cells. Neither intact IgM nor the IgG-like fragment enhanced the in vitro invasiveness of B16 melanoma cells across Matrigel-coated membranes. Our results, therefore, suggest that besides their beneficial anti-tumor effects, anti-tumor IgM antibodies may also promote the hematogenous dissemination of cancer cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Endoscopy in Canada: Proceedings of the National Roundtable: Toronto,Ontario, February 7, 2014

This 2014 roundtable discussion, hosted by the Canadian Association of General Surgeons, brought together general surgeons and gastroenterologists with expertise in endoscopy from across Canada to discuss the state of endoscopy in Canada. The focus of the roundtable was the evaluation of the competence of general surgeons at endoscopy, reviewing quality assurance parameters for high-quality endoscopy, measuring and assessing surgical resident preparedness for endoscopy practice, evaluating credentialing programs for the endosuite and predicting the future of endoscopic services in Canada. The roundtable noted several important observations. There exist inadequacies in both resident training and the assessment of competency in endoscopy. From these observations, several collaborative recommendations were then stated. These included the need for a formal and standardized system of both accreditation and training endoscopists.     

Ultrasound-guided intra-articular knee injection in an obese patient

A 35-yr-old woman was referred to our outpatient clinic for a right intra-articular knee aspiration and injection. She had a medical history notable for lymphedema and morbid obesity (Fig. 1). Her body mass index was recently calculated at greater than 60 kg/m(2). She had a history of four previous nonguided knee joint injections performed elsewhere that provided no significant improvement in pain. On physical examination, it was difficult to localize common knee joint bony landmarks, including the medial and lateral borders of the patella (Fig. 2). Consequently we opted to utilize ultrasound guidance for the knee joint injection via the technique described herein.     

Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial

Background

Novel cardioprotective strategies are required to improve clinical outcomes in high risk patients undergoing coronary artery bypass graft (CABG)?±?valve surgery. Remote ischemic preconditioning (RIC), in which brief episodes of non-lethal ischemia and reperfusion are applied to the arm or leg, has been demonstrated to reduce perioperative myocardial injury following CABG?±?valve surgery. Whether RIC can improve clinical outcomes in this setting is unknown and is investigated in the effect of remote ischemic preconditioning on clinical outcomes (ERICCA) trial in patients undergoing CABG surgery. (ClinicalTrials.gov Identifier: NCT01247545).

Methods

The ERICCA trial is a multicentre randomized double-blinded controlled clinical trial which will recruit 1,610 high-risk patients (Additive Euroscore ≥?5) undergoing CABG?±?valve surgery using blood cardioplegia via 27 tertiary centres over 2?years. The primary combined endpoint will be cardiovascular death, non-fatal myocardial infarction, coronary revascularization and stroke at 1?year. Secondary endpoints will include peri-operative myocardial and acute kidney injury, intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes of quality of life and exercise tolerance. Patients will be randomized to receive after induction of anesthesia either RIC (4 cycles of 5?min inflation to 200?mmHg and 5?min deflation of a blood pressure cuff placed on the upper arm) or sham RIC (4 cycles of simulated inflations and deflations of the blood pressure cuff).

Implications

The findings from the ERICCA trial have the potential to demonstrate that RIC, a simple, non-invasive and virtually cost-free intervention, can improve clinical outcomes in higher-risk patients undergoing CABG?±?valve surgery.