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Mesenchymal stem cells (MSCs) hold promising therapeutic potential in several clinical applications, mainly due to their paracrine activity. The implementation of future secretome-based therapeutic strategies requires the use of easily accessible MSCs sources that provide high numbers of cells with homogenous characteristics. MSCs obtained from induced pluripotent stem cells (iMSCs) have been put forward as an advantageous alternative to the gold-standard tissue sources, such as bone marrow (BM-MSCs). In this study, we aimed at comparing the secretome of BM-MSCs and iMSCs over long-term culture. For that, we performed a broad characterization of both sources regarding their identity, proteomic secretome analysis, as well as replicative senescence and associated phenotypes, including its effects on MSCs secretome composition and immunomodulatory action. Our results evidence a rejuvenated phenotype of iMSCs, which is translated into a superior proliferative capacity before the induction of replicative senescence. Despite this significant difference between iMSCs and BM-MSCs proliferation, both untargeted and targeted proteomic analysis revealed a similar secretome composition for both sources in pre-senescent and senescent states. These results suggest that shifting from the use of BM-MSCs to a more advantageous source, like iMSCs, may yield similar therapeutic effects as identified over the past years for this gold-standard MSC source.

Phase transition temperatures of three ionic liquids (ILs) with ammonium cations of different alkyl chain length and nitrate common anion were determined in this paper by differential scanning calorimetry. Thermal stability of these ILs in air and nitrogen atmosphere and the maximum operation temperatures of the compounds were also studied using a thermogravimetric analyser. Furthermore, thermophysical properties as density, viscosity, thermal conductivity, and heat capacity against temperature of these pure ionic liquids were determined and compared with the corresponding values for water saturated samples. For this purpose, different techniques were employed: for density and viscosity a rotational automated viscodensimeter; for thermal conductivity measurements a thermal conductimeter that follows the transient hot-wire method; and for heat capacity measurements a microdifferential scanning calorimeter. Different behaviours were observed depending on the analysed thermophysical properties. In case of dried samples, density and thermal conductivity decrease with alkyl chain; for saturated samples, same tendency is observed for density but is the opposite in case of thermal conductivity. Isobaric specific heat and viscosity increase with alkyl chain length in case of dried samples; for saturated samples same tendency is observed for the viscosity, whereas the tendency is the contrary in case of isobaric specific heat.

We consider an evolution equation involving the fractional powers, of order $s \in (0,1)$, of a symmetric and uniformly elliptic second order operator and Caputo fractional time derivative of order $\gamma \in (1,2]$. Since it has been shown useful for the design of numerical techniques for related problems, we also consider a quasi--stationary elliptic problem that comes from the realization of the spatial fractional diffusion as the Dirichlet-to-Neumann map for a nonuniformly elliptic problem posed on a semi--infinite cylinder. We provide existence and uniqueness results together with energy estimates for both problems. In addition, we derive regularity estimates both in time and space; the time--regularity results show that the usual assumptions made in the numerical analysis literature are problematic

Cancer of unknown primary site is a histologically confirmed cancer that manifests in advanced stage, with no identifiable primary site following standard diagnostic procedures. Patients are initially categorized based on the findings of the initial biopsy: adenocarcinoma, squamous-cell carcinoma, neuroendocrine carcinoma, and poorly differentiated carcinoma. Appropriate patient management requires understanding several clinical and pathological features that aid in identifying several subsets of patients with more responsive tumors.

Mycobacterium chelonae is a nontuberculous mycobacterium, classified as a Runyon type IV mycobacterium. In relation to humans, it is most commonly associated with tissue trauma or pulmonary infections. The majority of medical reports describe finding M. chelonae in the surgical setting, attributing infection to inadequate sterilization of surgical equipment. Symptoms are often nonspecific and include pain, erythema, and draining subcutaneous nodules and skin lesions. Therefore, the diagnosis of M. chelonae is often difficult to establish without prior suspicion of the disease, but can be confirmed with culture. We will describe the case of a 40-year-old female who contracted M. chelonae infection of the buttocks after abdominal liposuction and gluteal fat injection. We will describe her symptomatology, diagnosis, and successful treatment with surgical excision and antibiotics. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.

We present and analyze fully discrete fractional time stepping techniques for the solution of the micropolar Navier Stokes equations, which is a system of equations that describes the evolution of an incompressible fluid whose material particles possess both translational and rotational degrees of freedom. The proposed schemes uncouple the computation of the linear and angular velocity and the pressure. We develop a first order scheme which is unconditionally stable and delivers optimal convergence rates, and an almost unconditionally stable second order scheme.

The purpose of this work is the study of solution techniques for problems involving fractional powers of symmetric coercive elliptic operators in a bounded domain with Dirichlet boundary conditions. These operators can be realized as the Dirichlet to Neumann map for a degenerate/singular elliptic problem posed on a semi-infinite cylinder, which we analyze in the framework of weighted Sobolev spaces. Motivated by the rapid decay of the solution of this problem, we propose a truncation that is suitable for numerical approximation. We discretize this truncation using first degree tensor product finite elements. We derive a priori error estimates in weighted Sobolev spaces. The estimates exhibit optimal regularity but suboptimal order for quasi-uniform meshes. For anisotropic meshes, instead, they are quasi-optimal in both order and regularity. We present numerical experiments to illustrate the method's performance.

The so-called Stokes operator is an important tool in the analysis of the solutions of the Navier-Stokes equations and their numerical approximation. The aim of this note is to clarify certain properties of the fractional powers of this operator which are sometimes misused.

The DSC technique was used to characterise under laboratory conditions, the effect of a polymer substance, Firesorb, that tries to be used as a flame retardant in forest fires, over two different Galician soils (NW Spain). Samples of these soils with different doses of this retardant were heated in an oven at 230 and 350°C to simulate medium and high intensity fires, respectively. The effect of the retardant was determined as a result of the comparison between the enthalpy of combustion of the organic matter and the ignition temperature of these subsamples and the corresponding unheated and untreated ones. Both parameters, enthalpy of combustion and ignition temperature, were determined directly from the DSC experiments. The results showed that the effect of the retardant remains clear in heating at 230°C and the content of organic matter of the soil was a determining factor in its quantification. However the effect of the retardant in heating at high temperatures is almost null in both soils.

Introduction: The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo. However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear. Methods: In the present study, we have examined the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells. Results: The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome. Conclusions: Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications. © 2015 Teixeira et al., Portuguese Foundation for Science and Technology (FCT) (Ciência 2007 program and IF Development Grant (AJS); and pre-doctoral fellowships to FGT (SFRH/69637/ 2010) and SIA (SFRH/BD/81495/2011); Canada Research Chairs (LAB) and a SSE Postdoctoral Fellowship (KMP); The National Mass Spectrometry Network (RNEM) (REDE/1506/REM/2005); co-funded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), ao abrigo do Quadro de Referência Estratégico Nacional (QREN), através do Fundo Europeu de Desenvolvimento Regional (FEDER)., info:eu-repo/semantics/publishedVersion

A three-dimensional composite material was produced from microporous coralline origin hydroxyapatite (HA) microgranules, chitosan fibers and chitosan membrane. Cylindrical HA microgranules were oriented along channel direction within multichannel mould space and aligned particles were supported with fibers and a chitosan membrane. The positive replica of mould channels was clasp fixed to produce thicker scaffolds. Light microphotographs of the developed complex structure showed good adhesion between the HA particles, the fibers and the supporting membrane. The composite material showed 88% (w/w) swelling in one hour and preserved the complex structure of the original material upon long-term incubation in physiological medium. MEM extract test of HA chitosan complex showed no cell growth inhibition and cell viability assay (MTS) indicated over 90% cell viability.

The resonance neutron self-shielding factor, G res, is required in neutron metrology and activation data analysis. In a previous paper, the authors have shown that a dimensionless variable can be introduced which converts the dependence of G res on the physical and nuclear properties of the material samples into an universal curve, valid for the isolated resonances of any nuclide. This work presents a methodology based on the universal curve, which enables to calculate G res for a group of isolated resonances by weighting its individual contributions. A good agreement was reached with results calculated by the MCNP code and with experimental values for Mo foils and wires.

The interpretation of the sample activation in a nuclear reactor requires the knowledge of two corrective parameters: the thermal neutron self-shielding factor, G th, and the resonance neutron self-shielding factor, G res. The authors established a universal curve of G res for isolated resonances and various geometries. The present paper deals with the description of G th in foils, wires, spheres and cylinders by means of a universal curve on the basis of a dimensionless variable which includes the physical, nuclear and geometrical properties of the sample. The universal curve is in good agreement with the experimental and calculated values obtained from the literature.

CD26, a transmembrane ectoenzyme, is overexpressed on rheumatoid arthritis (RA) peripheral blood T cells. As it has been recently described that IL-12 and IL-15 upregulate CD26 in vitro, we hypothesized that this CD26 overexpression might be interleukin dependent. The concentrations of IL-12 and IL-15, and soluble CD26 and adenosine deaminase (enzymes related to CD26) were analyzed in the serum of 35 patients with active and inactive RA and of healthy control subjects. IL-12 and IL-15 levels were significantly higher in patients' serum, independently of disease activity, even in patients on steroid therapy, i.e., the present therapies cannot eradicate their origin. Soluble CD26 was significantly reduced and related to the disease activity. In particular, it correlated inversely with the number of swollen joints. Although these data did not support our hypothesis, they support that interleukins not only initiate RA pathology but they can also participate in the maintenance of this immune response.

A simulation study of a PGNAA measuring arrangement with a252Cf neutron source for the characterization of cement raw materials was carried out using the MCNP code to investigate the effect on the system response of varying the bulk density ρ and the water contentvw of samples of fixed dry composition. The source is placed at the centre of a lead cylinder of extemal radiusRPb. This cylinder is enclosed in a coaxial cylinder of polyethylene moderator of extermal radiusRin. The sample material is confined to the space between an outer cylindrical surface of radiusRout and the moderator cylinder. The first series of simulation runs was carried out for different sets of values ofRin,Rout and ρ, and constantvw. The system specific responseS (count rate per wt%) shows a broad maximum aroundTM=Rin-RPb=4 cm andTS=Rout-Rin=8.5 cm and a dependence on ρ that is almost linear in the region of the maximum. In a second series of runs the dependence ofS onvw was studied for a geometry corresponding to a real experiment described elsewhere and for a geometry for which the density saturation effect is already apparent. It is shown that when the sensitivity of the system is optimized both ρ andvw must be used as calibration parameters while in the low-sensitivity design regionvw can be used as the only calibration parameter.

Retinal abnormalities have been described in both animals and humans exposed to cocaine during development. The present study was designed to examine the morphological repercussions of neonatal exposure to cocaine on the developing retina of the rat. Male Wistar rats were given 15 mg/kg body weight per day of cocaine hydrochloride subcutaneously on postnatal days (PND) 0-6, 13 and 29 and sacrificed at PND 7, 14 or 30; controls were given saline. The retinas were processed for electron microscopy. Retinal quadrants were embedded flat and vertical semithin and ultrathin sections obtained. PND 7 sections showed discrete intraretinal hemorrhages, PND 14 sections showed massive intraretinal hemorrhages and images of ischemic necrosis in the nerve fiber layer and PND 30 sections showed cavity lesions in the hemorrhagic areas, gliosis and pigmented macrophage-rich epiretinal membranes; photoreceptor rosettes were also found. These results are the first morphological demonstration of retinal hemorrhages and associated epiretinal membranes following neonatal exposure to cocaine in the rat. These changes are probably related to the ischemia/hypoxia induced by cocaine.

Prompt gamma-neutron activation analysis, PGNAA, has been used to determine major and minor elements of bituminous coals. Calibration curves for H, C, N, Cl, Si, Ti, Al, Fe, Ca, Na, K, and S were obtained using six coals of different origin. The correlation coefficients are, in general, greater than 0.9 with the exception of C, N, and K. The γ-peak intensities were corrected for volume hydrogen content and normalised to the source intensity by using the 2615 keV γ-line from the (n, n′γ) reaction induced in the lead container of the Cf source. Elemental compositions of new coal samples were determined. In spite of the weak neutron source intensity, the comparison between the elemental concentrations measured by PGNAA and by conventional analysis show good agreement except for N, K, S and Ca.

Dear Editor, Prevention of deep venous thrombosis with its potentially disastrous pulmonary, cardiac, and occasionally cerebral manifestations is of utmost importance to physicians and surgeons alike. The incidence of this disease increases with the presence of risk factors such as venous stasis resulting from immobilization, vessel intima injury as well as a variety of hypercoagulable states that are caused by medications or congenital and acquired medical conditions. Methods of prevention include administration of chemical agents such as anticoagulants and the use of physical compression devices. All have shown to decrease the incidence of venous thrombosis either alone or in combination and have been used frequently when prolonged periods of immobilization are anticipated [1, 2]. The incidence of deep venous thrombosis has been thought to be low in the Chinese population [3, 4]. This has led to a debate regarding the necessity for chemical or mechanical prophylaxis against the development of thrombosis in this group of patients with the associated increase in cost, inconvenience, and increase in bleeding tendencies. Although more recent reports in the literature have demonstrated certain conditions associated with venous thromboembolism in the Chinese population where prophylaxis is recommended, such as in patients with a history of malignancy, orthopedic surgery, intravenous drug use, thrombophilia, pregnancy, and the use of oral contraceptives, a lower incidence of thrombosis does exist compared to Caucasians in Western countries [5, 6]. This difference in incidence and etiology is not clear. Proposed etiologies include a low level of APC resistance in the Chinese population compared to Caucasians. Having been involved in the practice of medicine both in Taiwan and the United States, we have noted a tremendous difference in the prevention measures taken against the development of deep venous thrombosis and continue to observe a low incidence of this disease. Guidelines have been set forth for deep vein thrombosis prophylaxis for the general population [7] but none specific for the Chinese population. Plastic surgery procedures, particularly microsurgical reconstruction, require prolonged periods of immobilization during and after surgery. We have patients in Taiwan who undergo 10 h procedures and are placed in bed rest confinement for 5 days postoperatively without any prophylactic measures taken against the development of deep venous thrombosis. Are we missing sub-clinical thromboses, or are they just not resulting in disastrous outcomes? Ann Hematol (2010) 89:93–94 DOI 10.1007/s00277-009-0765-z

The goal of this work is to pursue the research activity in BNC and the installation of a therapy facility in the position presently occupied by the thermal column. With these objectives the experimental studies in mice and cells are continuing while improvements in the facilities are created or prepared. For this effect: (1) the installation of lead shield in the vertical access of the thermal column, which resulted in an enhancement of the Φ th toD γ ratio, was performed, (2) the adaptation of a beam tube to deliver a dominantly thermal or epithermal beam in two possible beam openings is being done and (3) Monte Carlo calculations aiming at the optimization of the conditions for the therapy installation are in progress.