Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.     

WAIS-R Information subtest item bias for Canadian high school students.

The WAIS-R Information subtest was combined with 21 potential substitute Canadian content items and group-administered to 119 high school students ranging in age from 16 to 19 years. Seven acceptable substitute items were identified. Mean scores on the American items for the 16-17 and 18-19 age groups suggested that Canadians of these ages are not penalized by American content with respect to either Verbal or Full Scale IQ. Nevertheless, the research identified eight Information items, four easier and four more difficult than the standard WAIS-R implies. Similar results were noted in two previous studies of the WAIS-R, and indicate the extreme caution required for the clinical interpretation of intra test scatter. There is also evidence that item difficulty within the Information subtest may vary with the age of the subject. These results were considered indicative of the necessity for Canadian content Information items and the development of Canadian norms for an adapted WAIS-R Information subtest. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A VLIW processor with reconfigurable instruction set for embedded applications

This paper describes a new architecture for embedded reconfigurable computing, based on a very-long instruction word (VLIW) processor enhanced with an additional run-time configurable datapath. The reconfigurable unit is tightly coupled with the processor, featuring an application-specific instruction-set extension. Mapping computation intensive algorithmic portions on the reconfigurable unit allows a more efficient elaboration, thus leading to an improvement in both timing performance and power consumption. A test chip has been implemented in a standard 0.18-/spl mu/m CMOS technology. The test of a signal processing algorithmic benchmark showed speedups ranging from 4.3/spl times/ to 13.5/spl times/ and energy consumption reduced up to 92%.     

A Multicriteria Decision Support Methodology for Annual Rehabilitation Programs of Water Networks

Abstract:   This article provides an overview of a multicriteria decision support methodology for annual rehabilitation programs of water networks. A first set of criteria is formulated for the purpose of comparing and ranking rehabilitation projects. Each proposed criterion is a measure of a particular impact of the condition of a pipe. The ELECTRE TRI method is implemented for defining rehabilitation priorities . Two reference profiles are used to define the limits of three categories associated with three increasing priority levels. With these two reference profiles, applying the ELECTRE TRI method to an asset stock ( a set of pipes that are candidates for rehabilitation ) means assigning each pipe to one of six possible priority groups. A second set of criteria, based on the concept of efficiency, is proposed for comparing alternative rehabilitation programs ( subsets of the asset stock ).     

Novel and highly potent 5-HT3 receptor agonists based on a pyrroloquinoxaline structure

The synthesis and the biological evaluation of a series of novel pyrroloquinoxaline derivatives are described. In binding studies several compounds proved to be potent and selective 5-HT3 receptor ligands. The most active pyrroloquinoxalines, 11d and 11e, showed a subnanomolar affinity for 5-HT3 receptor and were able to functionally discriminate the central and peripheral 5-HT3 receptor, being agonists and antagonists, respectively. In functional studies ([14C]-guanidinium accumulation test in NG 108-15 cells, in vitro) most of the synthesized compounds showed clear-cut 5-HT3 agonist properties. In in vivo studies on the von Bezold-Jarisch reflex test (a peripheral interaction model) the behavior of the tested compounds ranged from agonist to antagonist, while clear agonist properties were obtained with 12a on cortical acetylcholine release in freely moving rats. Pharmacokinetic studies with 11e and 12c indicate that the compounds easily cross the blood-brain barrier (BBB) after systemic administration with a brain/plasma ratio of 17.5 and 37.5, respectively. Thus compounds 11e and 12c represent the most potent central 5-HT3 agonists identified to date that are able to cross the blood-brain barrier.     

Maternal serum screening for trisomy 18 in the first trimester of pregnancy

It is widely accepted that thrombocytopenia associated with liver cirrhosis is caused by increased platelet destruction in the enlarged spleen, but this issue has not yet been analysed sufficiently in terms of platelet production. Thrombopoietin is produced mainly in the liver and strongly promotes platelet production. We studied serum thrombopoietin and the levels of its mRNA in liver tissue of cirrhotic patients and also in a rat model of liver cirrhosis. Furthermore, to clarify the influence of the spleen, we investigated thrombopoietin mRNA in splenectomized rats. The serum thrombopoietin level in humans with liver cirrhosis was not significantly reduced instead of thrombocytopenia. The expression of thrombopoietin mRNA in liver tissue decreased with the progression of liver cirrhosis in both patients and the rat model and no compensatory expression was observed in other organs or non-parenchymal cells. The level of thrombopoietin mRNA did not differ significantly in splenectomized cirrhotic rats before or after administration of dimethylnitrosamine, but was lower than that in splenectomized rats without cirrhosis. We conclude that thrombocytopenia in liver cirrhosis is caused not only by platelet destruction but also by decreased platelet production, perhaps due to reduction of thrombopoietin mRNA in the liver.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

Preparation of nano-sized silicon carbide powder using thermal plasma

Nano-sized silicon carbide (SiC) powder was prepared by thermal plasma process using silicon tetrachloride (SiCl₄) and methane (CH₄). The synthesized powder was characterized by X-ray diffraction pattern, scanning electron microscopy, transmission electron microscopy, FT-IR spectroscopy and particle size analyzer. The powder was dominated by β-SiC including some of α-SiC and free carbon species. The quality of the powder was varied with process conditions such as the molar ratio of H/Si and C/Si, and collecting positions. It was known that the conversion to SiC was mainly affected by the addition of hydrogen gas because it promoted the decomposition and reduction of SiCL. CH₄ was easily decomposed to carbon species for the formation of SiC as well as removal of impure oxygen, but excessive carbon suppressed the formation of crystalline SiC and resulted in the solid carbon contamination. The optimum ratio of H/Si was approx. 26 and that of C/Si was 1.1. For collecting positions, the powder collected at the vessel and filter was preferable to that at the reaction tube. The average size of the powder synthesized was estimated to be below 100 nm and uniform in distribution.     

Update on the pharmacology of Spirulina (Arthrospira), an unconventional food

Spirulina (Arthrospira), a filamentous, unicellular alga, is a cyanobacterium grown in certain countries as food for human and animal consumption. It is also used to derive additives in pharmaceuticals and foods. This alga is a rich source of proteins, vitamins, amino acids, minerals, and other nutrients. Its main use, therefore, is as a food supplement. Over the last few years, however, it has been found to have many additional pharmacological properties. Thus, it has been experimentally proven, in vivo and in vitro that it is effective to treat certain allergies, anemia, cancer, hepatotoxicity, viral and cardiovascular diseases, hyperglycemia, hyperlipidemia, immunodeficiency, and inflammatory processes, among others. Several of these activities are attributed to Spirulina itself or to some of its components including fatty acids omega-3 or omega-6, beta-carotene, alpha-tocopherol, phycocyanin, phenol compounds, and a recently isolated complex, Ca-Spirulan (Ca-SP). This paper aims to update and critically review the results published over the last few years with regards to these properties. The conclusion is that even if this cyanobacterium has been one of the most extensively studied from the chemical, pharmacological and toxicological points of view, it is still necessary to expand the research in order to have more consistent data for its possible use in human beings.