Dysfunctional stem and progenitor cells impair fracture healing with age

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly

Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition

Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein-E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 min of laparotomy combined with a substantial blood loss (approximately 20% of total blood volume; 400 µl). The innominate artery was harvested 72 h after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6) and serum amyloid A (SAA) plasma levels were determined. Plaque load, vascular smooth muscle cell (VSMC) and macrophage content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture were assessed. High-dose atorvastatin (80 mg/kg body weight/day) was administered for 6 days starting 3 days prior to the double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein gp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased, peaking at 6 h after the intervention. SAA levels peaked at 24 h (n=4, P<0.01). Plaque volume increased significantly with the double hit compared to sham (n=8, P<0.01). More plaques were scored as complex or bearing signs of rupture after the double hit compared to sham (n=5-8, P<0.05). Relative VSMC and macrophage content remained unchanged. IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, P<0.01). Using this model, researchers will be able to further investigate the pathophysiology of perioperative plaque stability, which can result in myocardial infarction, and, additionally, to test potential protective strategies

Fractional variational problems depending on indefinite integrals and with delay

The aim of this paper is to exhibit a necessary and sufficient condition of optimality for functionals depending on fractional integrals and derivatives, on indefinite integrals and on presence of time delay. We exemplify with one example, where we nd analytically the minimizer

The supraclavicular flap for reconstruction of post-burn mentosternal contractures

Background: The thin and pliable skin of the neck is a region with multidirectional activity, and postburn scar contractures tend to form there easily. The supraclavicular flap is used to correct neck scar contractures. Its main vascular supply is the supraclavicular artery, and it can be harvested as either a skin pedicle flap or an island flap (vascular pedicle flap). Objective: In this article, a total of 41 flaps are studied retrospectively and their efficacy in reconstruction of post-burn neck scar contractures is discussed. Also donor-site morbidity, patient satisfaction, and complications were evaluated. Patients and Methods: Between November of 2004 and January of 2009, 41 supraclavicular flaps were used for reconstructions in 32 patients at the authors' hospital. Twenty-four of these flaps were skin pedicle flaps, and 17 were island flaps. The range of flap size was 18 ± 6 cm in length, and 9 ± 3 cm in width. Pre-expansion was performed in 14 flaps. Primary closure of donor site was performed in 35 flaps. Results: Thirty-seven of the 41 flaps survived completely, but there were three cases of distal necrosis (10-30), and one case of complete flap necrosis. Twenty-nine of the 32 patients were satisfied with both the functional and aesthetic results. Conclusions: Scarring of the neck produces problems with function, and appearance. In our view, the supraclavicular flap, a thin flap of good texture, is an excellent and highly reliable flap for covering defects of the anterior neck. This flap is easy to harvest, with good functional and aesthetic results. © 2013, Iranian Red Crescent Medical Journal

A novel hybrid spectral-variational iteration method (H-S-VIM) for solving nonlinear equations arising in heat transfer

WOS: 000346942900011The purpose of this study is to implement a new modification of the variational iteration method (H-S-VIM), which is a combination of spectral method and variational iteration method for heat transfer problems with high nonlinearity order. The merit of this method is that it does not require the solution of any linear or nonlinear system of equations unlike spectral method. Furthermore the proposed method is easy to implement and computationally very attractive. Here, H-S-VIM is used to solve an unsteady nonlinear convective-radiative equation containing two small parameters, and . It is observed that H-S-VIM may be implemented on other strongly nonlinear models of physical nature

Direct Method to Solve Differential-Algebraic Equations by Using the Operational Matrices of Chebyshev Cardinal Functions

A new and effective direct method to determine the numerical solution of linear and nonlinear differential-algebraic equations (DAEs) is proposed. The method consists of expanding the required approximate solution as the elements of Chebyshev cardinal functions. The operational matrices for the integration and product of the Chebyshev cardinal functions are presented. A general procedure for forming these matrices is given. These matrices play an important role in modelling of problems. By using these operational matrices together, a differentialalgebraic equation can be transformed to a system of algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the techniqu