Kinematic Behaviour of a Novel Pedicle Screw-Rod Fixation System for the Canine Lumbosacral Joint

Objective: To determine the biomechanical behaviour of a novel distraction-stabilization system, consisting of an intervertebral distraction bolt, polyaxial screws and connecting rods, in the canine lumbosacral spine. Study design: Biomechanical study. Sample population: Cadaveric canine lumbosacral spines (L4-Cd3) (N=8) Methods: Cadaveric lumbosacral spines were harvested, stripped of musculature, mounted on a 4-point bending jig, and tested in extension, flexion and lateral bending using non-destructive compressive axial loads (0-150N). Angular displacement was recorded from reflective optical trackers rigidly secured to L6, L7 and S1. Data for primary and coupled motion were collected from intact spines; after destabilization at L7-S1, and following surgical stabilisation with the new implant system. Results: As compared with the intact spine, laminectomy resulted in a modest increase in angular displacement at L6-L7 and a marked increase at L7-S1. Instrumentation significantly reduced motion at the operated level (L7-S1) with a concomitant increase at the adjacent level (L6-L7). Conclusion: The combination of a polyaxial pedicle screw-rod system and intervertebral spacer provides a versatile solution of surgical stabilisation of the lumbosacral joint following surgical decompression in the canine lumbosacral spine. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question. Clinical relevance: These results support the feasibility of using this new implant system for the management of degenerative lumbosacral disease in dogs. The increase in motion at L6-L7 may suggest the potential for adjacent level effects and clinical trials should be designed to address this question

The Large Zinc Finger Protein ZAS3 Is a Critical Modulator of Osteoclastogenesis

Mice deficient in the large zinc finger protein, ZAS3, show postnatal increase in bone mass suggesting that ZAS3 is critical in the regulation of bone homeostasis. Although ZAS3 has been shown to inhibit osteoblast differentiation, its role on osteoclastogenesis has not been determined. In this report we demonstrated the role of ZAS3 in bone resorption by examining the signaling mechanisms involved in osteoclastogenesis.Comparison of adult wild-type and ZAS3 knockout (ZAS3-/-) mice showed that ZAS3 deficiency led to thicker bones that are more resistant to mechanical fracture. Additionally, ZAS3-/- bones showed fewer osteoclasts and inefficient M-CSF/sRANKL-mediated osteoclastogenesis ex vivo. Utilizing RAW 264.7 pre-osteoclasts, we demonstrated that overexpression of ZAS3 promoted osteoclastogenesis and the expression of crucial osteoclastic molecules, including phospho-p38, c-Jun, NFATc1, TRAP and CTSK. Contrarily, ZAS3 silencing by siRNA inhibited osteoclastogenesis. Co-immunoprecipitation experiments demonstrated that ZAS3 associated with TRAF6, the major receptor associated molecule in RANK signaling. Furthermore, EMSA suggested that nuclear ZAS3 could regulate transcription by binding to gene regulatory elements.Collectively, the data suggested a novel role of ZAS3 as a positive regulator of osteoclast differentiation. ZAS3 deficiency caused increased bone mass, at least in part due to decreased osteoclast formation and bone resorption. These functions of ZAS3 were mediated via activation of multiple intracellular targets. In the cytoplasmic compartment, ZAS3 associated with TRAF6 to control NF-kB and MAP kinase signaling cascades. Nuclear ZAS3 acted as a transcriptional regulator for osteoclast-associated genes. Additionally, ZAS3 activated NFATc1 required for the integration of RANK signaling in the terminal differentiation of osteoclasts. Thus, ZAS3 was a crucial molecule in osteoclast differentiation, which might potentially serve as a target in the design of therapeutic interventions for the treatment of bone diseases related to increased osteoclast activity such as postmenopausal osteoporosis, Paget's disease, and rheumatoid arthritis

Household Contamination with Salmonella enterica1

Household contamination with Salmonella enterica increases when occupational exposure exists (cattle farms with known salmonellosis in cattle, a salmonella research laboratory, or a veterinary clinic experiencing an outbreak of salmonellosis). Fifteen of 55 (27.2%) vacuum cleaner bags from households with occupational exposure to S. enterica were positive versus 1 of 24 (4.2% without known exposure. Use of a carpet cleaner and several cleaners/disinfectants reduced, but failed to eliminate, S. enterica from artificially contaminated carpet

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Critical evaluation of stents in the peripheral arterial disease of the superficial femoral artery – focus on the paclitaxel eluting stent

Jason Litsky,1 Arijit Chanda,2 Erik Stilp,1 Alexandra Lansky,1 Carlos Mena11Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Section of Cardiology, Department of Internal Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The endovascular management of obstructive disease of the superficial femoral artery (SFA) is challenging due to unique anatomical and biomechanical forces. Obstructive lesions of the SFA make up the largest proportion of lesions leading to symptomatic peripheral arterial disease. Accordingly, endovascular treatment of SFA disease is becoming increasingly common and, in many cases, is the preferred initial therapy. The use of self-expanding nitinol stents have proven superior to percutaneous transluminal balloon angioplasty in the treatment of intermediate length SFA stenosis. However, achieving durable results, as well as attaining adequate therapy for long occlusions typically seen in clinical practice, remains problematic. Newer technologies, such as paclitaxel eluting stents, seem promising in improving outcomes.Keywords: Zilver PTX, self-expanding stent, atherosclerotic disease, superficial femoral arter