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.     

Major abdominal surgery and the clearance of lipid emulsions

Reaction of bacterial adhesins with complementary receptors on the surfaces of mucosal respiratory, gastrointestinal and genitourinary cells leads to bacterial adhesion to the human body. This is the first step in the sequence of events leading to infection. It has been observed that subinhibitory concentrations (sub-MICs) of some antibiotics are able to reduce bacterial adhesion. The pharmacokinetic curves of antibiotics show that these sub-MICs are present in tissues during a typical course of therapy. This study investigated the ability of sub-MICs of seven macrolides and four fluoroquinolones to reduce adhesiveness of Staphylococcus aureus to human buccal cells. The literature generally reports data for only one antibiotic at a time. To obtain an overall view of the findings of eleven antibiotics together, the data have been normalized according to the molecular weight of each antibiotic and the dose-effect curves determined.     

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.     

Comparison of morphologic assessment of hypertrophic cardiomyopathy by magnetic resonance versus echocardiographic imaging

To compare the value of echocardiography and magnetic resonance imaging (MRI) in the assessment of the amount and extent of hypertrophy in hypertrophic cardiomyopathy (HC) and, second, to correlate the degree of hypertrophy, as assessed by MRI, with clinical and electrocardiographic parameters, 30 consecutive patients (16 men and 14 women, aged 20 to 74 years) with HC were studied. Measurements of left ventricular wall thickness were performed at 11 predetermined segments (5 basal, 5 midventricular, and 1 apical) by 2-dimensional echocardiography and MRI. Two parameters derived from MRI studies were considered as indicators of the degree and extent of hypertrophy: (1) mean of the measured wall thickness at the 11 segments, and (2) the number of segments with thickness > 15 mm. Results showed that, from a total of 330 myocardial segments, thickness could be measured by echocardiography in 221 (67%), whereas MRI allowed measurement of 320 segments (97%). When compared with clinical and electrocardiographic data, no correlation was found regarding mean wall thickness and number of hypertrophied segments by MRI except for the presence of an abnormal electrocardiographic repolarization pattern. It is concluded that MRI allows a better assessment of the degree and extension of left ventricular hypertrophy than echocardiography in HC. Despite the precise information on hypertrophy provided by MRI, the amount and degree of hypertrophy bears no correlation with most of the clinical data in these patients.     

Geometric criteria of hydrogen bonds in proteins and identification of `bifurcated' hydrogen bonds

Empirical criteria for identification of hydrogen bonds wereanalyzed to produce a set of geometrically consistent criteria.For a data set of 30 structures, application of a set of purelygeometrical criteria, along with exclusion of abnormal backboneconformations, also excluded a common interaction of Ser/Thrside chains with Asp/Glu side chains ([ST]/[DE] pairs). Theseinteractions were termed `bifurcated hydrogen bonds/', whichimplies delocalization of a positively charged hydrogen of hydroxylbetween the two acceptor atoms of the carboxylic group. These`bifurcated/' interactions are among the most common packingpatterns for [ST]/[DE] pairs of side chains. Therefore, theidentification of hydrogen bonds cannot be based on geometricalcriteria only and requires introduction of some physico-chemicalcriteria.     

Effect of Dilution and Porosity on Self-Propagating High-Temperature Synthesis of Silicon Nitride

Self-propagating high-temperature synthesis is a very easy and low-cost method to synthesize Si₃N₄. The nitriding of silicon powder takes place in a self-sustained regime under high pressures of nitrogen with dilution of silicon by Si₃N₄. In this work effects of dilution and green-mixture porosity on combustion velocity and phase content of reaction products are studied. Results are compared with previous work of other authors and different behaviors are found. An explanation of these behaviors is given.     

Extending the power line LAN up to the neighborhood transformer

This article reports on the performance of audio, video, multimedia, and other high-data-rate in-home networking applications. The article starts by describing the problems encountered in power line communication channels in terms of frequency response and noise characteristics, and explains how in-home power line LANs can be extended to the neighborhood transformer. OFDM physical layers providing speeds of 45 Mb/s and 200 Mb/s as well as QoS and security are introduced. Finally, the results of large tests involving several thousands of nodes are described.     

How disorder can diminish avalanche risks: effect of size distribution

We study the behavior of disk assemblies with a variable disorder distribution. The packing is first consolidated and then continuously tilted very slowly. The amount of displaced disks for each tilted angle is recorded. Large displacements of the disks can occur due to some local or global mechanical instabilities. The definition of neighboring disks is based on radical (extension of Voronoï) tessellation rules to decompose, in a unique and perfectly defined manner, the two-dimensional space for polydisperse disks. In this way, by comparing the characteristics of stability for one disk to the neighboring ones for local ordered cluster, we can predict the global amount of displaced disks. Some tilting cycles have been performed to check the correlation between the instability of the packing structure (collective displacements) with micro and macro order parameters.     

Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation

BACKGROUND: Transplantation of blood or bone-marrow stem cells is the treatment of choice for selected patients with chronic myeloid leukaemia (CML). Transplantation is used with increasing frequency and success, but remains associated with substantial risks of morbidity and mortality. Other treatments with satisfactory short-term outcome are available. For appropriate counselling of patients, a rapid and simple way to assess risk is needed. METHODS: Data from 3142 patients (1873 [60%] male, 1269 [40%] female; mean age 34 years, range <1-60 years) treated with allogeneic blood or marrow transplants for CML between 1989 and 1997, reported to the European Group for Blood and Marrow Transplantation (EBMT), were used to develop and test a simple risk score based on previously reported major pretransplant risk factors: histocompatibility, stage of disease at time of transplantation, age and sex of donor and recipient, and time from diagnosis to transplantation. We analysed probabilities of survival, leukaemia-free survival, transplant-related mortality, and relapse incidence with respect to these risk factors. FINDINGS: At the time of analysis, 1922 (61%) of the 3142 patients were alive-1567 (65%) of those with HLA-identical sibling donors and 417 (57%) of those with unrelated donors. 1682 (54%) were alive without relapse. 1220 (39%) patients had died, 1013 (83%) of transplant-related causes, 207 (17%) of relapse. 447 (14%) patients had relapsed. The final scoring system was highly predictive for leukaemia-free survival, survival and transplant-related mortality. Survival at 5 years was 72%, 70%, 62%, 48%, 40%, 18%, and 22% for patients with scores 0, 1, 2, 3, 4, 5, and 6, respectively. Risk of transplant-related mortality was 20%, 23%, 31%, 46%, 51%, 71%, and 73%. Data showed the same trends for HLA-identical sibling transplants and unrelated transplants for transplants done in 1989-93 and 1994-96. INTERPRETATION: Pretransplant risk factors are cumulative for individual patients with CML having blood or marrow transplantation. A simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions.     

Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults

Exosomes are extracellular vesicles that contain nucleic acids, lipids and metabolites, and play a critical role in health and disease as mediators of intercellular communication. The majority of extracellular vesicles in the blood are platelet-derived. Compared to adults, neonatal platelets are hyporeactive and show impaired granule release, associated with defects in Soluble N-ethylmaleimide-sensitive fusion Attachment protein REceptor (SNARE) proteins. Since these proteins participate in biogenesis of exosomes, we investigated the potential differences between newborn and adult plasma-derived exosomes. Plasma-derived exosomes were isolated by ultracentrifugation of umbilical cord blood from full-term neonates or peripheral blood from adults. Exosome characterization included size determination by transmission electron microscopy and quantitative proteomic analysis. Plasma-derived exosomes from neonates were significantly smaller and contained 65% less protein than those from adults. Remarkably, 131 proteins were found to be differentially expressed, 83 overexpressed and 48 underexpressed in neonatal (vs. adult) exosomes. Whereas the upregulated proteins in plasma exosomes from neonates are associated with platelet activation, coagulation and granule secretion, most of the underexpressed proteins are immunoglobulins. This is the first study showing that exosome size and content change with age. Our findings may contribute to elucidating the potential “developmental hemostatic mismatch risk” associated with transfusions containing plasma exosomes from adults.