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Sample records for aggrecan type results

  1. Limitations of using aggrecan and type X collagen as markers of chondrogenesis in mesenchymal stem cell differentiation.

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    Mwale, Fackson; Stachura, Dorothy; Roughley, Peter; Antoniou, John

    2006-08-01

    The study was initially designed to differentiate human bone marrow-derived mesenchymal stem cells (MSC) into chondrocyte-like cells, for use in tissue engineering. We cultured MSCs in defined chondrogenic medium as pellet cultures supplemented with transforming growth factor (TGF)-beta1 or -beta3 and dexamethazone, as they are commonly used to promote in vitro chondrogenesis. Markers of chondrogenesis used were type II collagen and aggrecan, with type X collagen being used as a marker of late-stage chondrocyte hypertrophy (associated with endochondral ossification). Our results show that aggrecan is constitutively expressed by MSCs and that type X collagen is expressed as an early event. Furthermore, we found that type X collagen was expressed before type II collagen in some cases. This is surprising because it is understood that stem cells have to be differentiated into chondrocytes before they can become hypertrophic. Thus, caution must be exercised when using aggrecan and type X collagen as markers for chondrogenesis and chondrocyte hypertrophy, respectively, in association with stem cell differentiation from this source.

  2. The C-type lectin of the aggrecan G3 domain activates complement.

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    Camilla Melin Fürst

    Full Text Available Excessive complement activation contributes to joint diseases such as rheumatoid arthritis and osteoarthritis during which cartilage proteins are fragmented and released into the synovial fluid. Some of these proteins and fragments activate complement, which may sustain inflammation. The G3 domain of large cartilage proteoglycan aggrecan interacts with other extracellular matrix proteins, fibulins and tenascins, via its C-type lectin domain (CLD and has important functions in matrix organization. Fragments containing G3 domain are released during normal aggrecan turnover, but increasingly so in disease. We now show that the aggrecan CLD part of the G3 domain activates the classical and to a lesser extent the alternative pathway of complement, via binding of C1q and C3, respectively. The complement control protein (CCP domain adjacent to the CLD showed no effect on complement initiation. The binding of C1q to G3 depended on ionic interactions and was decreased in D2267N mutant G3. However, the observed complement activation was attenuated due to binding of complement inhibitor factor H to CLD and CCP domains. This was most apparent at the level of deposition of terminal complement components. Taken together our observations indicate aggrecan CLD as one factor involved in the sustained inflammation of the joint.

  3. In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.

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    Schneevoigt, J; Fabian, C; Leovsky, C; Seeger, J; Bahramsoltani, M

    2017-02-01

    The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells. © 2016 Blackwell Verlag GmbH.

  4. Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection.

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    Cikach, Frank S; Koch, Christopher D; Mead, Timothy J; Galatioto, Josephine; Willard, Belinda B; Emerton, Kelly B; Eagleton, Matthew J; Blackstone, Eugene H; Ramirez, Francesco; Roselli, Eric E; Apte, Suneel S

    2018-03-08

    Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair.

  5. Extraction of aggrecan-peptide from cartilage by tissue autolysis.

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    Nakano, Takuo; Srichamroen, Anchalee; Ozimek, Lech

    2014-01-01

    Aggrecan is a cartilage specific proteoglycan containing chondroitin sulfate (CS) and keratan sulfate (KS). CS is an acidic polysaccharide having wide range of applications in pharmaceutical, cosmetic, and food industries. CS is extracted from cartilage by tissue proteolysis with an exogenous proteinase or by activating endogenous proteinases (autolysis) to release aggrecan-peptides from the tissue. This review is focused on the latter technique. Bovine nasal and tracheal cartilages, and broiler chicken sternum cartilage have been used for autolysis studies. To extract aggrecan-peptide, cartilage tissues are cut into small pieces, and incubated in a monovalent or divalent salt solution (e.g., 0.1 M sodium or calcium acetate) at pH 4.5 and 37 °C for 7 - 24 h. Most (~80% or more) of total tissue uronic acid, a constituent sugar of aggrecan, is extracted and released into the salt solution during incubation. Reextraction of the tissue residue results in release of a small amount of uronic acid. Aggrecan-peptides purified using anion exchange chromatography are large compounds containing CS and KS. On gel chromatography, they are excluded from the column of Sephacryl S-300. Chemical composition analysis demonstrated that aggrecan-peptides from either bovine or chicken cartilage contain >90% CS with small amount (autolysis has been used as a plate coating antigen in enzyme- linked immunosorbent assay (ELISA) to determine KS.

  6. An ARGS-aggrecan assay for analysis in blood and synovial fluid

    DEFF Research Database (Denmark)

    Larsson, S; Lohmander, Stefan; Struglics, A

    2014-01-01

    OBJECTIVE: To validate a modified ligand-binding assay for the detection of aggrecanase generated aggrecan fragments with the ARGS neoepitope in synovial fluid (SF) and blood, and to verify the identity of aggrecan fragments found in blood. DESIGN: An enzyme-linked immunosorbent assay (ELISA....... Aggrecan was purified from serum and plasma pools and analysed by Western blot. RESULTS: The limits of quantification for the ARGS-aggrecan assay was between 0.2 and 0.025 pmol ARGS/ml, and the sensitivity of the assay was improved two-fold compared to when using a standard purified from human donors...... similar, and correlated (r(S) = 0.773, P assay is highly sensitive and suited for analysis...

  7. Expression of aggrecan components in perineuronal nets in the mouse cerebral cortex

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    Hiroshi Ueno

    2018-06-01

    Full Text Available Specific regions of the cerebral cortex are highly plastic in an organism’s lifetime. It is thought that perineuronal nets (PNNs regulate plasticity, but labeling for Wisteria floribunda agglutinin (WFA, which is widely used to detect PNNs, is observed throughout the cortex. The aggrecan molecule—a PNN component—may regulate plasticity, and may also be involved in determining region-specific vulnerability to stress. To clarify cortical region-specific plasticity and vulnerability, we qualitatively analyzed aggrecan-positive and glycosylated aggrecan-positive PNNs in the mature mouse cerebral cortex. Our findings revealed the selective expression of both aggrecan-positive and glycosylated aggrecan-positive PNNs in the cortex. WFA-positive PNNs expressed aggrecan in a region-specific manner in the cortex. Furthermore, we observed variable distributions of PNNs containing WFA- and aggrecan-positive molecules. Together, our findings suggest that PNN components and their function differ depending on the cortical region, and that aggrecan molecules may be involved in determining region-specific plasticity and vulnerability in the cortex. Keywords: Aggrecan, Brain region-specific, Chondroitin sulfate proteoglycan, Extracellular matrix, Perineuronal nets, Plasticity

  8. Immunohistochemistry Evaluation of TGF-β1, SOX-9, Type II Collagen and Aggrecan in Cartilage Lesions Treated with Conditioned Medium of Umbilical Cord Mesencyhmal Stem Cells in Wistar Mice (Rattus novergicus

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    Bintang Soetjahjo

    2018-01-01

    Full Text Available Currently, umbilical cord mesenchymal stem cells have the potential to be used as treatment options for any cartilage lesion. This research aimed to evaluate the effects of conditioned medium from umbilical cord mesenchymal stem cells (UC-MSC on damaged cartilage through the expression of proteins TGF-β1, SOX-9, type II collagen and aggrecan, which are known to be related to chondrogenesis. UC-MSC were isolated from 19-days-pregnant Wistar mice and were cultured using the standard procedure to obtain 80% confluence. Subsequently, the culture was confirmed through a microscopic examination that was driven to be an embryoid body to obtain a pre-condition medium. This research utilized 3-month-old male Wistar mice and was categorized into 6 groups (3 control and 3 treatment groups. Each animal had surgery performed to create a femur condyle cartilage defect. The treatment groups were administered a dose of stem cells at 1 mL/kg. Next, immunohistochemical (IHC staining was performed to examine the expression of TGF-β1, SOX-9, type II collagen and aggrecan in the 2nd, 3rd, and 4th month of evaluation. The results were analyzed statistically using ANOVA test. For each of the treatment groups, there was increased expression (p < 0.05 in all proteins TGF-β1, SOX-9, type II collagen and aggrecan when compared with control groups at the 2nd, 3rd, and 4th month of evaluation. Pre-conditioned medium from UC-MSC potentially increases the expression of TGF-β1, SOX-9, type II collagen and aggrecan in the damaged cartilage of Wistar mice.

  9. Juvenile Hippocampal CA2 Region Expresses Aggrecan

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    Asako Noguchi

    2017-05-01

    Full Text Available Perineuronal nets (PNNs are distributed primarily around inhibitory interneurons in the hippocampus, such as parvalbumin-positive interneurons. PNNs are also present around excitatory neurons in some brain regions and prevent plasticity in these neurons. A recent study demonstrated that PNNs also exist around mouse hippocampal pyramidal cells, which are the principle type of excitatory neurons, in the CA2 subregion and modulate the excitability and plasticity of these neurons. However, the development of PNNs in the CA2 region during postnatal maturation was not fully investigated. This study found that a main component of PNNs, aggrecan, existed in the pyramidal cell layer of the putative CA2 subarea prior to the appearance of the CA2 region, which was defined by the CA2 marker protein regulator of G protein signaling 14 (RGS14. We also found that aggrecan immunoreactivity was more evident in the anterior sections of the CA2 area than the posterior sections, which suggests that the function of CA2 PNNs varies along the anterior-posterior axis.

  10. Aggrecan structure in amphibian cartilage

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    Covizi D.Z.

    2000-01-01

    Full Text Available The structure of the large proteoglycan present in the bullfrog epiphyseal cartilage was studied by immunochemical and biochemical methods. The isolated monomer showed a polydisperse behavior on Sepharose CL2B, with a peak at Kav = 0.14. Chondroitin sulfate chains were identified by HPLC analysis of the products formed by chondroitinase digestion and mercuric acetate treatment. These chains have approximately 38 disaccharides, a Di45:Di68 ratio of 1.6 and GalNAc4S + GalNAc4,6S are the main non-reducing terminals. Keratan sulfate was identified by the use of two monoclonal antibodies in Western blots after chondroitinase ABC treatment. A keratan sulfate-rich region (~110 kDa was isolated by sequential treatment with chondroitinase ABC and proteases. We also employed antibodies in Western blotting experiments and showed that the full length deglycosylated core protein is about 300 kDa after SDS-PAGE. Domain-specific antibodies revealed the presence of immunoreactive sites corresponding to G1/G2 and G3 globular domains and the characterization of this large proteoglycan as aggrecan. The results indicate the high conservation of the aggrecan domain structure in this lower vertebrate.

  11. Evidence of a novel aggrecan-degrading activity in cartilage: Studies of mice deficient in both ADAMTS-4 and ADAMTS-5.

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    Rogerson, Fraser M; Stanton, Heather; East, Charlotte J; Golub, Suzanne B; Tutolo, Leonie; Farmer, Pamela J; Fosang, Amanda J

    2008-06-01

    To characterize aggrecan catabolism and the overall phenotype in mice deficient in both ADAMTS-4 and ADAMTS-5 (TS-4/TS-5 Delta-cat) activity. Femoral head cartilage from the joints of TS-4/TS-5 Delta-cat mice and wild-type mice were cultured in vitro, and aggrecan catabolism was stimulated with either interleukin-1alpha (IL-1alpha) or retinoic acid. Total aggrecan release was measured, and aggrecanase activity was examined by Western blotting using neoepitope antibodies for detecting cleavage at EGE 373-374 ALG, SELE 1279-1280 GRG, FREEE 1467-1468 GLG, and AQE 1572-1573 AGEG. Aggrecan catabolism in vivo was examined by Western blotting of cartilage that had been extracted immediately ex vivo. TS-4/TS-5 Delta-cat mice were viable, fertile, and phenotypically normal. TS-4/TS-5 Delta-cat cartilage explants did not release aggrecan in response to IL-1alpha, and there was no detectable increase in aggrecanase neoepitopes. TS-4/TS-5 Delta-cat cartilage explants released aggrecan in response to retinoic acid. There was no retinoic acid-stimulated cleavage at either EGE 373-374 ALG or AQE 1572-1573 AGEG. There was a low level of cleavage at SELE 1279-1280 GRG and major cleavage at FREEE 1467-1468 GLG. Ex vivo, cleavage at FREEE 1467-1468 GLG was substantially reduced, but still present, in TS-4/TS-5 Delta-cat mouse cartilage compared with wild-type mouse cartilage. An aggrecanase other than ADAMTS-4 and ADAMTS-5 is expressed in mouse cartilage and is up-regulated by retinoic acid but not IL-1alpha. The novel aggrecanase appears to have different substrate specificity from either ADAMTS-4 or ADAMTS-5, cleaving E-G bonds but not E-A bonds. Neither ADAMTS-4 nor ADAMTS-5 is required for normal skeletal development or aggrecan turnover in cartilage.

  12. The Development and Activity-Dependent Expression of Aggrecan in the Cat Visual Cortex

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    Sengpiel, F.; Beaver, C. J.; Crocker-Buque, A.; Kelly, G. M.; Matthews, R. T.; Mitchell, D. E.

    2013-01-01

    The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus (dLGN). During development, aggrecan expression increases in the dLGN with a time course that matches the decline in plasticity. Moreover, examination of tissue from selectively visually deprived cats shows that expression is activity dependent, suggesting a role for aggrecan in the termination of the sensitive period. Here, we demonstrate for the first time that the onset of aggrecan expression in area 17 also correlates with the decline in experience-dependent plasticity in visual cortex and that this expression is experience dependent. Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan-positive neurons in the extragranular layers, but not in layer IV. This effect was reversible as dark-reared animals that were subsequently exposed to light showed normal numbers of Cat-301-positive cells. The reduction in aggrecan following certain early deprivation regimens is the first biochemical correlate of the functional changes to the γ-aminobutyric acidergic system that have been reported following early deprivation in cats. PMID:22368089

  13. Changes in Cytokines and Aggrecan ARGS Neoepitope in Synovial Fluid and Serum and in C-Terminal Crosslinking Telopeptide of Type II Collagen and N-Terminal Crosslinking Telopeptide of Type I Collagen in Urine Over Five Years After Anterior Cruciate Ligament Rupture

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    Struglics, André; Larsson, Staffan; Kumahashi, Nobuyuki

    2015-01-01

    OBJECTIVE: To prospectively monitor levels of proinflammatory cytokines and aggrecan ARGS neoepitope in synovial fluid and serum as well as levels of C-terminal crosslinking telopeptide of type II collagen (CTX-II) and N-terminal crosslinking telopeptide of type I collagen (NTX-I) in urine after ...

  14. Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation by Human Chondrocytes.

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    Ismail, Heba M; Yamamoto, Kazuhiro; Vincent, Tonia L; Nagase, Hideaki; Troeberg, Linda; Saklatvala, Jeremy

    2015-07-01

    Aggrecan enables articular cartilage to bear load and resist compression. Aggrecan loss occurs early in osteoarthritis and rheumatoid arthritis and can be induced by inflammatory cytokines such as interleukin-1 (IL-1). IL-1 induces cleavage of specific aggrecans characteristic of the ADAMTS proteinases. The aim of this study was to identify the intracellular signaling pathways by which IL-1 causes aggrecan degradation by human chondrocytes and to investigate how aggrecanase activity is controlled by chondrocytes. We developed a cell-based assay combining small interfering RNA (siRNA)-induced knockdown with aggrecan degradation assays. Human articular chondrocytes were overlaid with bovine aggrecan after transfection with siRNAs against molecules of the IL-1 signaling pathway. After IL-1 stimulation, released aggrecan fragments were detected with AGEG and ARGS neoepitope antibodies. Aggrecanase activity and tissue inhibitor of metalloproteinases 3 levels were measured by enzyme-linked immunosorbent assay. Low-density lipoprotein receptor-related protein 1 (LRP-1) shedding was analyzed by Western blotting. ADAMTS-5 is a major aggrecanase in human chondrocytes, regulating aggrecan degradation in response to IL-1. The tumor necrosis factor receptor-associated 6 (TRAF-6)/transforming growth factor β-activated kinase 1 (TAK-1)/MKK-4 signaling axis is essential for IL-1-induced aggrecan degradation, while NF-κB is not. Of the 3 MAPKs (ERK, p38, and JNK), only JNK-2 showed a significant role in aggrecan degradation. Chondrocytes constitutively secreted aggrecanase, which was continuously endocytosed by LRP-1, keeping the extracellular level of aggrecanase low. IL-1 induced aggrecanase activity in the medium in a JNK-2-dependent manner, possibly by reducing aggrecanase endocytosis, because IL-1 caused JNK-2-dependent shedding of LRP-1. The signaling axis TRAF-6/TAK-1/MKK-4/JNK-2 mediates IL-1-induced aggrecanolysis. The level of aggrecanase is controlled by its

  15. Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid

    NARCIS (Netherlands)

    Sivan, S.S.; Tsitron, E.; Wachtel, E.; Roughley, P.J.; Sakkee, N.; Ham, F. van der; Groot, J.de; Roberts, S.; Maroudas, A.

    2006-01-01

    We have used the racemization of aspartic acid as a marker for the "molecular age" of aggrecan components of the human intervertebral disc matrix (aggregating and non-aggregating proteoglycans as well as the different buoyant density fractions of aggrecan). By measuring the D/L Asp ratio of the

  16. Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

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    Sondergaard Bodil-Cecilie

    2009-12-01

    Full Text Available Abstract Background Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. Findings Bovine cartilage explants were cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM and tumor necrosis factor alpha (TNFα. In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo-epitope specific immunoassays; (1 sandwich 342FFGVG-G2 ELISA, (2 competition NITEGE373ELISA (3 sandwich G1-NITEGE373 ELISA (4 competition 374ARGSV ELISA, and (5 sandwich 374ARGSV-G2 ELISA all detecting aggrecan fragments, and (6 sandwich CTX-II ELISA, detecting C-telopeptides of type II collagen. We found that (1 aggrecanase-derived aggrecan fragments are released in the early (day 2-7 and mid phase (day 9-14 into the supernatant from bovine explants cultures stimulated with catabolic cytokines, (2 the release of NITEGE373 neo-epitopes are delayed compared to the corresponding 374ARGSV fragments, (3 the MMP inhibitor GM6001 did not reduce the release of aggrecanase-derived fragment, but induced a further delay in the release of these fragments, and finally (4 the MMP-derived aggrecan and type II collagen fragments were released in the late phase (day 16-21 only. Conclusion Our data support the model, that aggrecanases and MMPs act independently in the processing of the aggrecan molecules, and furthermore that suppression of MMP-activity had little if

  17. Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

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    A. Hanyecz

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA, and CD4+ T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.

  18. The interaction between aggrecan gene VNTR polymorphism and obesity in predicting incident symptomatic lumbar disc herniation.

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    Cong, Lin; Zhu, Yue; Pang, Hao; Guanjun, T U

    2014-01-01

    An association between aggrecan gene variable number of tandem repeats polymorphism (VNTR) and symptomatic lumbar disc herniation (LDH) has been reported in Chinese Han of Northern China, and obesity had previously been suspected of causing severe LDH. However, the interaction between aggrecan VNTR and obesity in symptomatic LDH has not been well studied. To examine the interaction between aggrecan VNTR and obesity in the susceptibility of symptomatic LDH, 259 participants participated in this study and donated a blood sample. The disease group comprised 61 patients already diagnosed with symptomatic LDH. The control group consisted of 198 healthy blood donors without symptoms of LDH who were not diagnosed with LDH. The aggrecan gene VNTR region was analyzed using polymerase chain reaction. The data indicated that between the two groups, participants carrying one or two alleles ≤25 repeats who were non-obese people showed a 1.057-fold increase in risk for symptomatic LDH (p = 0.895, changing the number of repeat alleles to 25 repeats who were obese people showed an 1.061-fold higher risk (p = 0.885, adding obesity to the mix alone did not demonstrably increase the risk of LDH), while participants carrying one or two alleles ≤25 repeats who were obese people showed a 4.667-fold increase in risk for symptomatic LDH (p = 0.0003, adding obesity plus changing the repeat allele number significantly increased the risk of LDH by 4.667). Overall, the findings suggest an underlying interaction between aggrecan VNTR and obesity in symptomatic LDH.

  19. A Sulfated Glycosaminoglycan Linkage Region is a Novel Type of Human Natural Killer-1 (HNK-1 Epitope Expressed on Aggrecan in Perineuronal Nets.

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    Keiko Yabuno

    Full Text Available Human natural killer-1 (HNK-1 carbohydrate (HSO3-3GlcAβ1-3Galβ1-4GlcNAc-R is highly expressed in the brain and required for learning and neural plasticity. We previously demonstrated that expression of the HNK-1 epitope is mostly abolished in knockout mice for GlcAT-P (B3gat1, a major glucuronyltransferase required for HNK-1 biosynthesis, but remained in specific regions such as perineuronal nets (PNNs in these mutant mice. Considering PNNs are mainly composed of chondroitin sulfate proteoglycans (CSPGs and regulate neural plasticity, GlcAT-P-independent expression of HNK-1 in PNNs is suggested to play a role in neural plasticity. However, the function, structure, carrier glycoprotein and biosynthetic pathway for GlcAT-P-irrelevant HNK-1 epitope remain unclear. In this study, we identified a unique HNK-1 structure on aggrecan in PNNs. To determine the biosynthetic pathway for the novel HNK-1, we generated knockout mice for GlcAT-S (B3gat2, the other glucuronyltransferase required for HNK-1 biosynthesis. However, GlcAT-P and GlcAT-S double-knockout mice did not exhibit reduced HNK-1 expression compared with single GlcAT-P-knockout mice, indicating an unusual biosynthetic pathway for the HNK-1 epitope in PNNs. Aggrecan was purified from cultured cells in which GlcAT-P and -S are not expressed and we determined the structure of the novel HNK-1 epitope using liquid chromatography/mass spectrometry (LC/MS as a sulfated linkage region of glycosaminoglycans (GAGs, HSO3-GlcA-Gal-Gal-Xyl-R. Taken together, we propose a hypothetical model where GlcAT-I, the sole glucuronyltransferase required for synthesis of the GAG linkage, is also responsible for biosynthesis of the novel HNK-1 on aggrecan. These results could lead to discovery of new roles of the HNK-1 epitope in neural plasticity.

  20. The Effect of Soy Isoflavone on the Proliferation and Differentiation of Adipose-Derived Mesenchymal Stem Cells into Chondrocytes and Expression of Collagen II and Aggrecan Genes

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    Fatemeh Bamdadpasand Shekarsarayi

    2017-03-01

    Full Text Available Background and Objectives: Due to the lack of blood vessels in cartilage tissue, its damage is not repairable. This study was conducted to investigate the effect of soy isoflavone on proliferation and differentiation of adipose-derived mesenchymal stem cells into chondrocytes and expression of collagen II and aggrecan genes. Methods: In this experimental study, human subcutaneous fat was obtained during liposuction and incubated with collagenase enzyme (type 1 for the breakdown of collagen, and collagenase was deactivated by DMEM medium, and was cultured in the cell sediment after centrifugation, the cells were isolated after the third passage, were placed in chondrogenic medium for differentiate into the cartilage, and were divided into three groups, including control, treatment with TGF-β1, and treatment with soy isoflavones tablets. The tablets were dissolved in distilled water, sterilized by passing through a 0.2 um filter and were added to the culture medium. After 48 hours, cell viability was determined by MTT assay, and after 14 days, collagen II and aggrecan gene expressions were assessed by real-time PCR technique. Data were statistically analyzed by one-way ANOVA and Tukey's post-hoc test using SPSS 20 and p<0.05. Results: The results of MTT assay showed a significant increase in viability in the TGF-β1 group compared to the control and soy isoflavone groups (p<0.05. The RT-PCR indicated a significant increase in the expression of collagen II and aggrecan genes in isoflavones and TGF-β1 groups compared to the control group, and also, the mean CT associated with collagen II gene had a significant increase in isoflavone and TGF-β1groups compared to the control group (p<0.05. Conclusion: Soy in culture medium increases the expression of collagen II and aggrecan genes and cell proliferation, but this increase is not high compared to the TGF-β1 group.

  1. The concentration, gene expression, and spatial distribution of aggrecan in canine articular cartilage, meniscus, and anterior and posterior cruciate ligaments: a new molecular distinction between hyaline cartilage and fibrocartilage in the knee joint.

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    Valiyaveettil, Manojkumar; Mort, John S; McDevitt, Cahir A

    2005-01-01

    The concentration, spatial distribution, and gene expression of aggrecan in meniscus, articular cartilage, and the anterior and posterior cruciate ligaments (ACL and PCL) was determined in the knee joints of five mature dogs. An anti-serum against peptide sequences specific to the G1 domain of aggrecan was employed in competitive-inhibition ELISA of guanidine HCl extracts and immunofluorescence microscopy. Gene expression was determined by Taqman real-time PCR. The concentration of aggrecan in articular cartilage (240.1 +/- 32 nMol/g dry weight) was higher than that in meniscus (medial meniscus: 33.4 +/- 4.3 nMol/g) and ligaments (ACL: 6.8 +/- 0.9 nMol/g). Aggrecan was more concentrated in the inner than the outer zone of the meniscus. Aggrecan in meniscus showed an organized, spatial network, in contrast to its diffuse distribution in articular cartilage. Thus, differences in the concentration, gene expression, and spatial distribution of aggrecan constitute another molecular distinction between hyaline cartilage and fibrocartilage of the knee.

  2. Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838).

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    Morawski, M; Brückner, G; Jäger, C; Seeger, G; Künzle, H; Arendt, T

    2010-02-03

    The Madagascan tenrecs (Afrotheria), an ancient mammalian clade, are characterized by unique brain anatomy. Striking features are an expanded paleocortex but a small and poorly differentiated neocortex devoid of a distinct granular layer IV. To investigate the organization of cortical areas we analyzed extracellular matrix components in perineuronal nets (PNs) using antibodies to aggrecan, lectin staining and hyaluronan-binding protein. Selected subcortical regions were studied to correlate the cortical patterns with features in evolutionary conserved systems. In the neocortex, paleocortex and hippocampus PNs were associated with nonpyramidal neurons. Quantitative analysis in the cerebral cortex revealed area-specific proportions and laminar distribution patterns of neurons ensheathed by PNs. Cortical PNs showed divergent structural phenotypes. Diffuse PNs forming a cotton wool-like perisomatic rim were characteristic of the paleocortex. These PNs were associated with a dense pericellular plexus of calretinin-immunoreactive fibres. Clearly contoured PNs were devoid of a calretinin-positive plexus and predominated in the neocortex and hippocampus. The organization of the extracellular matrix in subcortical nuclei followed the widely distributed mammalian type. We conclude that molecular properties of the aggrecan-based extracellular matrix are conserved during evolution of mammals; however, the matrix scaffold is adapted to specific wiring patterns of cortical and subcortical neuronal networks. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan

    Science.gov (United States)

    Watanabe, Hideto; Nakata, Ken; Kimata, Koji; Nakanishi, Isao; Yamada, Yoshihiko

    1997-01-01

    Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (−/−) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/−) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration. PMID:9192671

  4. Enriched housing enhances recovery of limb placement ability and reduces aggrecan-containing perineuronal nets in the rat somatosensory cortex after experimental stroke.

    Directory of Open Access Journals (Sweden)

    Alexandre Madinier

    Full Text Available Stroke causes life long disabilities where few therapeutic options are available. Using electrical and magnetic stimulation of the brain and physical rehabilitation, recovery of brain function can be enhanced even late after stroke. Animal models support this notion, and housing rodents in an enriched environment (EE several days after experimental stroke stimulates lost brain function by multisensory mechanisms. We studied the dynamics of functional recovery of rats with a lesion to the fore and hind limb motor areas induced by photothrombosis (PT, and with subsequent housing in either standard (STD or EE. In this model, skilled motor function is not significantly enhanced by enriched housing, while the speed of recovery of sensori-motor function substantially improves over the 9-week study period. In particular, this stroke lesion completely obliterates the fore and hind limb placing ability when visual and whisker guidance is prevented, a deficit that persists for up to 9 weeks of recovery, but that is markedly restored within 2 weeks by enriched housing. Enriched housing after stroke also leads to a significant loss of perineuronal net (PNN immunoreactivity; detection of aggrecan protein backbone with AB1031 antibody was decreased by 13-22%, and labelling of a glycan moiety of aggrecan with Cat-315 antibody was reduced by 25-30% in the peri-infarct area and in the somatosensory cortex, respectively. The majority of these cells are parvalbumin/GABA inhibitory interneurons that are important in sensori-information processing. We conclude that damage to the fore and hind limb motor areas provides a model of loss of limb placing response without visual guidance, a deficit also seen in more than 50% of stroke patients. This loss is amenable to recovery induced by multiple sensory stimulation and correlates with a decrease in aggrecan-containing PNNs around inhibitory interneurons. Modulating the PNN structure after ischemic damage may provide new

  5. Dwarfism in homozygous Agc1CreERT mice is associated with decreased expression of aggrecan.

    Science.gov (United States)

    Rashid, Harunur; Chen, Haiyan; Hassan, Quamarul; Javed, Amjad

    2017-10-01

    Aggrecan (Acan), a large proteoglycan is abundantly expressed in cartilage tissue. Disruption of Acan gene causes dwarfism and perinatal lethality of homozygous mice. Because of sustained expression of Acan in the growth plate and articular cartilage, Agc Cre model has been developed for the regulated ablation of target gene in chondrocytes. In this model, the IRES-CreERT-Neo-pgk transgene is knocked-in the 3'UTR of the Acan gene. We consistently noticed variable weight and size among the Agc Cre littermates, prompting us to examine the cause of this phenotype. Wild-type, Cre-heterozygous (Agc +/Cre ), and Cre-homozygous (Agc Cre/Cre ) littermates were indistinguishable at birth. However, by 1-month, Agc Cre/Cre mice showed a significant reduction in body weight (18-27%) and body length (19-22%). Low body weight and dwarfism was sustained through adulthood and occurred in both genders. Compared with wild-type and Agc +/Cre littermates, long bones and vertebrae were shorter in Agc Cre/Cre mice. Histological analysis of Agc Cre/Cre mice revealed a significant reduction in the length of the growth plate and the thickness of articular cartilage. The amount of proteoglycan deposited in the cartilage of Agc Cre/Cre mice was nearly half of the WT littermates. Analysis of gene expression indicates impaired differentiation of chondrocyte in hyaline cartilage of Agc Cre/Cre mice. Notably, both Acan mRNA and protein was reduced by 50% in Agc Cre/Cre mice. A strong correlation was noted between the level of Acan mRNA and the body length. Importantly, Agc +/Cre mice showed no overt skeletal phenotype. Thus to avoid misinterpretation of data, only the Agc +/Cre mice should be used for conditional deletion of a target gene in the cartilage tissue. © 2017 Wiley Periodicals, Inc.

  6. Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments

    DEFF Research Database (Denmark)

    Wang, Bijue; Chen, Pingping; Jensen, Anne-Christine Bay

    2009-01-01

    BACKGROUND: Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggreca......BACKGROUND: Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP......- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. FINDINGS: Bovine cartilage explants were...... cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM) and tumor necrosis factor alpha (TNFalpha). In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo...

  7. In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model.

    Science.gov (United States)

    Horbert, Victoria; Xin, Long; Foehr, Peter; Brinkmann, Olaf; Bungartz, Matthias; Burgkart, Rainer H; Graeve, T; Kinne, Raimund W

    2018-02-01

    Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

  8. Type II collagen C2C epitope in human synovial fluid and serum after knee injury

    DEFF Research Database (Denmark)

    Kumahashi, N; Swärd, P; Larsson, S

    2015-01-01

    PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235...... = 0.403, P type II collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P ... with an immediate and sustained local degradation of type II collagen....

  9. Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease

    Science.gov (United States)

    Than, Khoi D.; Rahman, Shayan U.; Wang, Lin; Khan, Adam; Kyere, Kwaku A.; Than, Tracey T.; Miyata, Yoshinari; Park, Yoon-Shin; La Marca, Frank; Kim, Hyungjin M.; Zhang, Huina; Park, Paul; Lin, Chia-Ying

    2014-01-01

    BACKGROUND CONTEXT A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein-2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to up-regulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE To develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING Laboratory investigation. METHODS Disc injury was induced in 272 rats via 21-gauge needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the MRI index (number of pixels multiplied by corresponding image densities) was determined. Histologically, disc spaces were read by 3 blinded scorers employing a previously described histological grading scale. Genetically, nuclei pulposi were harvested and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. This project was supported by Grant No. R01 AR056649 from NIAMS/NIH. There are no other financial conflicts of interest to report. RESULTS Radiologically, discs treated with 5 mg/mL simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks post-treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL simvastatin in hydrogel demonstrated improved grades in comparison to discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control. CONCLUSIONS Degenerate discs treated with 5 mg/mL simvastatin in a hydrogel carrier demonstrated

  10. Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

    Science.gov (United States)

    Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

    2016-01-01

    During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

  11. ELISA for the core protein of the cartilage large aggregating proteoglycan, aggrecan: comparison with the concentrations of immunogenic keratan sulphate in synovial fluid, serum and urine

    DEFF Research Database (Denmark)

    Møller, H J; Larsen, F S; Ingemann-Hansen, T

    1994-01-01

    ELISA. The within-assay and between-assay coefficients of variation were 4.9-8.9% and 11.1-13.0%, respectively. The mean concentrations of core protein in synovial fluid, serum and urine were 76.4 micrograms/ml, 104.0 ng/ml and 81.0 ng/ml, respectively. In synovial fluids the concentrations were closely......Immunological assays for fragments of the cartilage large aggregating proteoglycan, aggrecan, have been widely used to monitor cartilage turnover. These assays have commonly employed the monoclonal keratan sulphate antibody, 5D4. Keratan sulphate, however, is present in many tissues and 5D4...

  12. Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNFα inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Hetland, Merete Lund; Sørensen, Inge Juul

    2010-01-01

    The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated...... with tumor necrosis factor-alpha (TNFα) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNFα inhibitor therapy (infliximab, n=38; etanercept, n=8...

  13. Changes in content and synthesis of collagen types and proteoglycans in osteoarthritis of the knee joint and comparison of quantitative analysis with Photoshop-based image analysis.

    Science.gov (United States)

    Lahm, Andreas; Mrosek, Eike; Spank, Heiko; Erggelet, Christoph; Kasch, Richard; Esser, Jan; Merk, Harry

    2010-04-01

    The different cartilage layers vary in synthesis of proteoglycan and of the distinct types of collagen with the predominant collagen Type II with its associated collagens, e.g. types IX and XI, produced by normal chondrocytes. It was demonstrated that proteoglycan decreases in degenerative tissue and a switch from collagen type II to type I occurs. The aim of this study was to evaluate the correlation of real-time (RT)-PCR and Photoshop-based image analysis in detecting such lesions and find new aspects about their distribution. We performed immunohistochemistry and histology with cartilage tissue samples from 20 patients suffering from osteoarthritis compared with 20 healthy biopsies. Furthermore, we quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorimetrically. Using Adobe Photoshop the digitized images of histology and immunohistochemistry stains of collagen type I and II were stored on an external data storage device. The area occupied by any specific colour range can be specified and compared in a relative manner directly from the histogram using the "magic wand tool" in the select similar menu. In the image grow menu gray levels or luminosity (colour) of all pixels within the selected area, including mean, median and standard deviation, etc. are depicted. Statistical Analysis was performed using the t test. With the help of immunohistochemistry, RT-PCR and quantitative RT- PCR we found that not only collagen type II, but also collagen type I is synthesized by the cells of the diseased cartilage tissue, shown by increasing amounts of collagen type I mRNA especially in the later stages of osteoarthritis. A decrease of collagen type II is visible especially in the upper fibrillated area of the advanced osteoarthritic samples, which leads to an overall decrease. Analysis of proteoglycan showed a loss of the overall content and a quite uniform staining in

  14. Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.

    Science.gov (United States)

    Guillén-García, Pedro; Rodríguez-Iñigo, Elena; Guillén-Vicente, Isabel; Caballero-Santos, Rosa; Guillén-Vicente, Marta; Abelow, Stephen; Giménez-Gallego, Guillermo; López-Alcorocho, Juan Manuel

    2014-04-01

    We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.

  15. Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications

    Directory of Open Access Journals (Sweden)

    DH Rosenzweig

    2017-03-01

    Full Text Available Autologous NP cell implantation is a potential therapeutic avenue for intervertebral disc (IVD degeneration. However, monolayer expansion of cells isolated from surgical samples may negatively impact matrix production by way of dedifferentiation. Previously, we have used a continuous expansion culture system to successfully preserve a chondrocyte phenotype. In this work, we hypothesised that continuous expansion culture could also preserve nucleus pulposus (NP phenotype. We confirmed that serial passaging drove NP dedifferentiation by significantly decreasing collagen type II, aggrecan and chondroadherin (CHAD gene expression, compared to freshly isolated cells. Proliferation, gene expression profile and matrix production in both culture conditions were compared using primary bovine NP cells. Both standard culture and continuous culture produced clinically relevant cell populations. However, continuous culture cells maintained significantly higher collagen type II, aggrecan and CHAD transcript expression levels. Also, continuous expansion cells generated greater amounts of proteoglycan, collagen type II and aggrecan protein deposition in pellet cultures. To our surprise, continuous expansion of human intervertebral disc cells – isolated from acute herniation tissue – produced less collagen type II, aggrecan and CHAD genes and proteins, compared to standard culture. Also, continuous culture of cells isolated from young non-degenerate tissue did not preserve gene and protein expression, compared to standard culture. These data indicated that primary bovine and human NP cells responded differently to continuous culture, where the positive effects observed for bovine cells did not translate to human cells. Therefore, caution must be exercised when choosing animal models and cell sources for pre-clinical studies.

  16. The effect of estrogen on the expression of cartilage-specific genes in the chondrogenesis process of adipose-derived stem cells

    Directory of Open Access Journals (Sweden)

    Farzaneh Sadeghi

    2015-01-01

    Full Text Available Background: During adolescence, sex hormones play an important role in regulating proliferation, differentiation, maturation, and the scheduled death of chondrocytes. Although some studies have reported the regulatory role of estrogen in the development and progression of cartilage, some of the mechanisms still remain unclear, including the role of estrogen in the expression of cartilage-specific genes in chondrogenesis process, which we cover in this study. Materials and Methods: In the present study, we used adipose-derived stem cells (ADSCs to differentiate into cartilage. Differentiated cartilage cells were used in the control (without estrogen E2 in the culture medium and experimental (with estrogen in the culture medium groups to evaluate the expression of type II collagen and aggrecan as chondrogenic genes markers, with -real-time polymerase chain reaction technique. Results: Our results indicated that estrogen leads to inhibition of type II collagen gene expression and reduction of aggrecan gene expression. Conclusion: Therefore, estrogen probably has negative effects on chondrogenesis process of ADSCs.

  17. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    Energy Technology Data Exchange (ETDEWEB)

    Kabiri, Azadeh, E-mail: z_kabiri@resident.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esfandiari, Ebrahim, E-mail: esfandiari@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Hashemibeni, Batool, E-mail: hashemibeni@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Kazemi, Mohammad, E-mail: m_kazemi@med.mui.ac.i [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Mardani, Mohammad, E-mail: mardani@med.mui.ac.ir [Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences (Iran, Islamic Republic of); Esmaeili, Abolghasem, E-mail: abesmaeili@yahoo.com [Cell, Molecular and Developmental Biology Division, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan (Iran, Islamic Republic of)

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We investigated effects of FGF-2 on hADSCs. Black-Right-Pointing-Pointer We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. Black-Right-Pointing-Pointer FGF-2 induces chondrogenesis in hADSCs, which Bullet Increasing information will decrease quality if hospital costs are very different. Black-Right-Pointing-Pointer The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  18. Effects of FGF-2 on human adipose tissue derived adult stem cells morphology and chondrogenesis enhancement in Transwell culture

    International Nuclear Information System (INIS)

    Kabiri, Azadeh; Esfandiari, Ebrahim; Hashemibeni, Batool; Kazemi, Mohammad; Mardani, Mohammad; Esmaeili, Abolghasem

    2012-01-01

    Highlights: ► We investigated effects of FGF-2 on hADSCs. ► We examine changes in the level of gene expressions of SOX-9, aggrecan and collagen type II and type X. ► FGF-2 induces chondrogenesis in hADSCs, which •Increasing information will decrease quality if hospital costs are very different. ► The result of this study may be beneficial in cartilage tissue engineering. -- Abstract: Injured cartilage is difficult to repair due to its poor vascularisation. Cell based therapies may serve as tools to more effectively regenerate defective cartilage. Both adult mesenchymal stem cells (MSCs) and human adipose derived stem cells (hADSCs) are regarded as potential stem cell sources able to generate functional cartilage for cell transplantation. Growth factors, in particular the TGF-b superfamily, influence many processes during cartilage formation, including cell proliferation, extracellular matrix synthesis, maintenance of the differentiated phenotype, and induction of MSCs towards chondrogenesis. In the current study, we investigated the effects of FGF-2 on hADSC morphology and chondrogenesis in Transwell culture. hADSCs were obtained from patients undergoing elective surgery, and then cultured in expansion medium alone or in the presence of FGF-2 (10 ng/ml). mRNA expression levels of SOX-9, aggrecan and collagen type II and type X were quantified by real-time polymerase chain reaction. The morphology, doubling time, trypsinization time and chondrogenesis of hADSCs were also studied. Expression levels of SOX-9, collagen type II, and aggrecan were all significantly increased in hADSCs expanded in presence of FGF-2. Furthermore FGF-2 induced a slender morphology, whereas doubling time and trypsinization time decreased. Our results suggest that FGF-2 induces hADSCs chondrogenesis in Transwell culture, which may be beneficial in cartilage tissue engineering.

  19. Osteochondritis dissecans (OCD), an endoplasmic reticulum storage disease?

    DEFF Research Database (Denmark)

    Skagen, Peter Storgaard; Horn, T; Kruse, H A

    2011-01-01

    in chondrocytes and extracellular matrix of cartilage from OCD patients. Abnormal type II collagen heterofibrils in "bundles" and chondrocytes with abnormal accumulation of matrix proteins in distended rough endoplasmic reticulum were typical findings. Further, Von Kossa staining and TEM showed empty lacunae...... close to mineralized "islands" in the cartilage and hypertrophic chondrocytes containing accumulated matrix proteins. Immunostaining revealed: (1) that types I, II, VI and X collagens and aggrecans were deposited intracellulary and (2) co-localization within the islands of types I, II, X collagens...... and aggrecan indicating that hypertrophic chondrocytes express a phenotype of bone cells during endochondral ossification. Types I, VI and X collagens were also present across the entire dissecates suggesting that chondrocytes were dedifferentiated. DNA sequencings were non-conclusive, only single nucleotide...

  20. Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells.

    Science.gov (United States)

    Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S; Chen, Faye H

    2012-04-01

    Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention.

  1. CARTILAGE OLIGOMERIC MATRIX PROTEIN ENHANCES MATRIX ASSEMBLY DURING CHONDROGENESIS OF HUMAN MESENCHYMAL STEM CELLS

    Science.gov (United States)

    Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S.; Chen, Faye H.

    2011-01-01

    Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate-hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. PMID:22095699

  2. Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components

    Directory of Open Access Journals (Sweden)

    Chang Qing

    2011-04-01

    Full Text Available Chondrocytes and bone marrow mesenchymal stem cells (BMSCs are frequently used as seed cells in cartilage tissue engineering. In the present study, we determined if the co-culture of rabbit articular chondrocytes and BMSCs in vitro promotes the expression of cartilaginous extracellular matrix and, if so, what is the optimal ratio of the two cell types. Cultures of rabbit articular chondrocytes and BMSCs were expanded in vitro and then cultured individually or at a chondrocyte:BMSC ratio of 4:1, 2:1, 1:1, 1:2, 1:4 for 21 days and cultured in DMEM/F12. BMSCs were cultured in chondrogenic induction medium. Quantitative real-time RT-PCR and Western blot were used to evaluate gene expression. In the co-cultures, type II collagen and aggrecan expression increased on days 14 and 21. At the mRNA level, the expression of type II collagen and aggrecan on day 21 was much higher in the 4:1, 2:1, and 1:1 groups than in either the articular chondrocyte group or the induced BMSC group, and the best ratio of co-culture groups seems to be 2:1. Also on day 21, the expression of type II collagen and aggrecan proteins in the 2:1 group was much higher than in all other groups. The results demonstrate that the co-culture of rabbit chondrocytes and rabbit BMSCs at defined ratios can promote the expression of cartilaginous extracellular matrix. The optimal cell ratio appears to be 2:1 (chondrocytes:BMSCs. This approach has potential applications in cartilage tissue engineering since it provides a protocol for maintaining and promoting seed-cell differentiation and function.

  3. Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components.

    Science.gov (United States)

    Qing, Chang; Wei-ding, Cui; Wei-min, Fan

    2011-04-01

    Chondrocytes and bone marrow mesenchymal stem cells (BMSCs) are frequently used as seed cells in cartilage tissue engineering. In the present study, we determined if the co-culture of rabbit articular chondrocytes and BMSCs in vitro promotes the expression of cartilaginous extracellular matrix and, if so, what is the optimal ratio of the two cell types. Cultures of rabbit articular chondrocytes and BMSCs were expanded in vitro and then cultured individually or at a chondrocyte:BMSC ratio of 4:1, 2:1, 1:1, 1:2, 1:4 for 21 days and cultured in DMEM/F12. BMSCs were cultured in chondrogenic induction medium. Quantitative real-time RT-PCR and Western blot were used to evaluate gene expression. In the co-cultures, type II collagen and aggrecan expression increased on days 14 and 21. At the mRNA level, the expression of type II collagen and aggrecan on day 21 was much higher in the 4:1, 2:1, and 1:1 groups than in either the articular chondrocyte group or the induced BMSC group, and the best ratio of co-culture groups seems to be 2:1. Also on day 21, the expression of type II collagen and aggrecan proteins in the 2:1 group was much higher than in all other groups. The results demonstrate that the co-culture of rabbit chondrocytes and rabbit BMSCs at defined ratios can promote the expression of cartilaginous extracellular matrix. The optimal cell ratio appears to be 2:1 (chondrocytes:BMSCs). This approach has potential applications in cartilage tissue engineering since it provides a protocol for maintaining and promoting seed-cell differentiation and function.

  4. Overexpression of Galnt3 in chondrocytes resulted in dwarfism due to the increase of mucin-type O-glycans and reduction of glycosaminoglycans.

    Science.gov (United States)

    Yoshida, Carolina Andrea; Kawane, Tetsuya; Moriishi, Takeshi; Purushothaman, Anurag; Miyazaki, Toshihiro; Komori, Hisato; Mori, Masako; Qin, Xin; Hashimoto, Ayako; Sugahara, Kazuyuki; Yamana, Kei; Takada, Kenji; Komori, Toshihisa

    2014-09-19

    Galnt3, UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3, transfers N-acetyl-D-galactosamine to serine and threonine residues, initiating mucin type O-glycosylation of proteins. We searched the target genes of Runx2, which is an essential transcription factor for chondrocyte maturation, in chondrocytes and found that Galnt3 expression was up-regulated by Runx2 and severely reduced in Runx2(-/-) cartilaginous skeletons. To investigate the function of Galnt3 in chondrocytes, we generated Galnt3(-/-) mice and chondrocyte-specific Galnt3 transgenic mice under the control of the Col2a1 promoter-enhancer. Galnt3(-/-) mice showed a delay in endochondral ossification and shortened limbs at embryonic day 16.5, suggesting that Galnt3 is involved in chondrocyte maturation. Galnt3 transgenic mice presented dwarfism, the chondrocyte maturation was retarded, the cell cycle in chondrocytes was accelerated, premature chondrocyte apoptosis occurred, and the growth plates were disorganized. The binding of Vicia villosa agglutinin, which recognizes the Tn antigen (GalNAc-O-Ser/Thr), was drastically increased in chondrocytes, and aggrecan (Acan) was highly enriched with Tn antigen. However, safranin O staining, which recognizes glycosaminoglycans (GAGs), and Acan were severely reduced. Chondroitin sulfate was reduced in amount, but the elongation of chondroitin sulfate chains had not been severely disturbed in the isolated GAGs. These findings indicate that overexpression of Galnt3 in chondrocytes caused dwarfism due to the increase of mucin-type O-glycans and the reduction of GAGs, probably through competition with xylosyltransferases, which initiate GAG chains by attaching O-linked xylose to serine residues, suggesting a negative effect of Galnt family proteins on Acan deposition in addition to the positive effect of Galnt3 on chondrocyte maturation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Fourier transform infrared imaging and infrared fiber optic probe spectroscopy identify collagen type in connective tissues.

    Directory of Open Access Journals (Sweden)

    Arash Hanifi

    Full Text Available Hyaline cartilage and mechanically inferior fibrocartilage consisting of mixed collagen types are frequently found together in repairing articular cartilage. The present study seeks to develop methodology to identify collagen type and other tissue components using Fourier transform infrared (FTIR spectral evaluation of matrix composition in combination with multivariate analyses. FTIR spectra of the primary molecular components of repair cartilage, types I and II collagen, and aggrecan, were used to develop multivariate spectral models for discrimination of the matrix components of the tissues of interest. Infrared imaging data were collected from bovine bone, tendon, normal cartilage, meniscus and human repair cartilage tissues, and composition predicted using partial least squares analyses. Histology and immunohistochemistry results were used as standards for validation. Infrared fiber optic probe spectral data were also obtained from meniscus (a tissue with mixed collagen types to evaluate the potential of this method for identification of collagen type in a minimally-invasive clinical application. Concentration profiles of the tissue components obtained from multivariate analysis were in excellent agreement with histology and immunohistochemistry results. Bone and tendon showed a uniform distribution of predominantly type I collagen through the tissue. Normal cartilage showed a distribution of type II collagen and proteoglycan similar to the known composition, while in repair cartilage, the spectral distribution of both types I and II collagen were similar to that observed via immunohistochemistry. Using the probe, the outer and inner regions of the meniscus were shown to be primarily composed of type I and II collagen, respectively, in accordance with immunohistochemistry data. In summary, multivariate analysis of infrared spectra can indeed be used to differentiate collagen type I and type II, even in the presence of proteoglycan, in

  6. Mast cell-restricted, tetramer-forming tryptases induce aggrecanolysis in articular cartilage by activating matrix metalloproteinase-3 and -13 zymogens.

    Science.gov (United States)

    Magarinos, Natalia J; Bryant, Katherine J; Fosang, Amanda J; Adachi, Roberto; Stevens, Richard L; McNeil, H Patrick

    2013-08-01

    Mouse mast cell protease (mMCP)-6-null C57BL/6 mice lost less aggrecan proteoglycan from the extracellular matrix of their articular cartilage during inflammatory arthritis than wild-type (WT) C57BL/6 mice, suggesting that this mast cell (MC)-specific mouse tryptase plays prominent roles in articular cartilage catabolism. We used ex vivo mouse femoral head explants to determine how mMCP-6 and its human ortholog hTryptase-β mediate aggrecanolysis. Exposure of the explants to recombinant hTryptase-β, recombinant mMCP-6, or lysates harvested from WT mouse peritoneal MCs (PMCs) significantly increased the levels of enzymatically active matrix metalloproteinases (MMP) in cartilage and significantly induced aggrecan loss into the conditioned media, relative to replicate explants exposed to medium alone or lysates collected from mMCP-6-null PMCs. Treatment of cartilage explants with tetramer-forming tryptases generated aggrecan fragments that contained C-terminal DIPEN and N-terminal FFGVG neoepitopes, consistent with MMP-dependent aggrecanolysis. In support of these data, hTryptase-β was unable to induce aggrecan release from the femoral head explants obtained from Chloe mice that resist MMP cleavage at the DIPEN↓FFGVG site in the interglobular domain of aggrecan. In addition, the abilities of mMCP-6-containing lysates from WT PMCs to induce aggrecanolysis were prevented by inhibitors of MMP-3 and MMP-13. Finally, recombinant hTryptase-β was able to activate latent pro-MMP-3 and pro-MMP-13 in vitro. The accumulated data suggest that human and mouse tetramer-forming tryptases are MMP convertases that mediate cartilage damage and the proteolytic loss of aggrecan proteoglycans in arthritis, in part, by activating the zymogen forms of MMP-3 and MMP-13, which are constitutively present in articular cartilage.

  7. Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro.

    Science.gov (United States)

    Ying, Xiaozhou; Zhang, Wei; Cheng, Shaowen; Nie, Pengfei; Cheng, Xiaojie; Shen, Yue; Wang, Wei; Xue, Enxing; Chen, Qingyu; Kou, Dongquan; Peng, Lei; Zhang, Yu; Lu, Chuanzhu

    2012-11-01

    Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10(-7), 10(-6) and 10(-5) M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro. BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue. The cell viability was not significantly impaired until up to a concentration of 10(-5) M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10(-6) M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10(-5) M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10(-7) and 10(-6) M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10(-7)-10(-5) M nicotine (P < 0.05). It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.

  8. [Effects of nicotine on bone marrow stromal cells proliferation and differentiation of chondrocyte in vitro].

    Science.gov (United States)

    Ying, Xiao-zhou; Peng, Lei; Cheng, Shao-wen; Chen, Qing-yu; Zhang, Wei; Kou, Dong-quan; Shen, Yue

    2011-11-01

    To examine the effects of various concentration of nicotine on bone marrow stromal cells (BMSCs) proliferation and differentiation of cartilaginous in vitro. BMSCs was obtained from femoral bone and tibia of New-Zealand albino rabbit. The cells of the 3rd generation were used in study. Different concentration of nicotine (0, 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) M) were added into BMSCs. BMSCs proliferation was analyzed by MTT assay at the 1, 4, 7, 14 days. The expression of collagen type II and aggrecan as the marker genes of cartilaginous differentiation from BMSCs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Microscope showed that BMSCs transformed from round to fusiform shape. The concentration of nicotine in 1 x 10(-7), 1 x 10(-6) M had a significant positive effect on cell proliferation and the expression of type II collagen in a time-dependent manner when supplemented in commonly used induction media (P<0.05). Concentrations of nicotine in 1 x 10(-7) can promote the expression of aggrecan at the 7th day after induction,and in 1 x 10(-5) M may inhibit the expression of type II collagen and aggrecan. It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing cartilaginous differentiation capacity of BMSCs in cartilage tissue engineering.

  9. An immunohistochemical study of the triangular fibrocartilage complex of the wrist: regional variations in cartilage phenotype

    Science.gov (United States)

    Milz, S; Sicking, B; Sprecher, C M; Putz, R; Benjamin, M

    2007-01-01

    The triangular fibrocartilage complex (TFCC) transmits load from the wrist to the ulna and stabilizes the distal radioulnar joint. Damage to it is a major cause of wrist pain. Although its basic structure is well established, little is known of its molecular composition. We have analysed the immunohistochemical labelling pattern of the extracellular matrix of the articular disc and the meniscal homologue of the TFCC in nine elderly individuals (age range 69–96 years), using a panel of monoclonal antibodies directed against collagens, glycosaminoglycans, proteoglycans and cartilage oligomeric matrix protein (COMP). Although many of the molecules (types I, III and VI collagen, chondroitin 4 sulphate, dermatan sulphate and keratan sulphate, the oversulphated epitope of chondroitin 6 sulphate, versican and COMP) were found in all parts of the TFCC, aggrecan, link protein and type II collagen were restricted to the articular disc and to entheses. They were thus not a feature of the meniscal homologue. The shift in tissue phenotype within the TFCC, from a fibrocartilaginous articular disc to a more fibrous meniscal homologue, correlates with biomechanical data suggesting that the radial region is stiff and subject to considerable stress concentration. The presence of aggrecan, link protein and type II collagen in the articular disc could explain why the TFCC is destroyed in rheumatoid arthritis, given that it has been suggested that autoimmunity to these antigens results in the destruction of articular cartilage. The differential distribution of aggrecan within the TFCC is likely to be reflected by regional differences in water content and mobility on the radial and ulnar side. This needs to be taken into account in the design of improved MRI protocols for visualizing this ulnocarpal complex of the wrist. PMID:17532798

  10. Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2013-01-01

    Full Text Available We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105 cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

  11. Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair.

    Science.gov (United States)

    Lazarini, Mariana; Bordeaux-Rego, Pedro; Giardini-Rosa, Renata; Duarte, Adriana S S; Baratti, Mariana Ozello; Zorzi, Alessandro Rozim; de Miranda, João Batista; Lenz Cesar, Carlos; Luzo, Ângela; Olalla Saad, Sara Teresinha

    2017-10-01

    Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

  12. Use of synovium-derived stromal cells and chitosan/collagen type I scaffolds for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Gong Zhongcheng; Lin Zhaoquan [Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054 (China); Xiong Hui; Long Xing; Wei Lili; Li Jian; Wu Yang, E-mail: xinglong1957@yahoo.com.c [State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079 (China)

    2010-10-01

    The objective was to investigate synovium-derived stromal cells (SDSCs) coupled with chitosan/collagen type I (CS/COL-I) scaffolds for cartilage engineering. CS/COL-I scaffolds were fabricated through freeze-drying and cross-linked by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. SDSCs were isolated from synovium and cultured onto CS/COL-I scaffolds, constructs of which were incubated in serum-free chondrogenic medium with sequential application of TGF-{beta}1 and bFGF for up to 21 days and then implanted into nude mice. The physical characteristics of the scaffolds were examined. The quality of the in vitro constructs was assessed in terms of DNA content by PicoGreen assay and cartilaginous matrix by histological examination. The implants of the constructs were evaluated by histological and immunohistochemical examinations and reverse transcription PCR. Results indicated that the CS/COL-I scaffold showed porous structures, and the DNA content of SDSCs in CS/COL-I scaffolds increased at 1 week culture time. Both of the constructs in vitro and the implants were examined with positive stained GAGs histologically and the implants with positive collagen type II immunohistochemically. RT-PCR of the implants indicated that aggrecan and collagen type II expressed. It suggested that SDSCs coupled with CS/COL-I scaffolds treated sequentially with TGF-{beta}1 and bFGF in vitro were highly competent for engineered cartilage formation in vitro and in vivo.

  13. Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

    Science.gov (United States)

    Tie, Kai; Zhang, Xianrong; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Wang, Hui; Chen, Liaobin

    2016-02-01

    This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/kg/d from gestational d 11 to 20. The female adult offspring with or without PNE were forced with a strenuous treadmill running for 6 wk to induce OA. Nicotine's effects on fetal articular chondrocytes were studied by exposing chondrocytes to nicotine for 10 d, and dihydro-β-erythroidine, a selective α4β2-nicotinic acetylcholine receptor (nAChR) inhibitor, was used to identify the change of nicotine's effect. For adult offspring, increased cartilage destruction and accelerated OA progression were observed in the PNE group with running; the expression of α1 chain of type II collagen (Col2A1), aggrecan, SRY-type high mobility group box 9 (Sox9), and IGF1 signaling molecules in the cartilage of PNE offspring were decreased. For fetuses, elevated serum corticosteroid and nicotine levels and suppressed IGF1 levels were observed; expression of Col2A1, aggrecan, Sox9, and IGF1 were reduced. The result of chondrocytes revealed that nicotine impeded the expression of Col2A1, aggrecan, and IGF1; blocking α4β2-nAChR rescued nicotine's suppression. In conclusion, PNE increases the susceptibility of adult offspring to OA; the potential mechanism involves IGF1 low-functional programming in articular cartilage caused directly by the action of nicotine on α4β2-nAChR. © FASEB.

  14. A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies.

    Science.gov (United States)

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Hansen, Ole Møller; Kristiansen, Asger Albæk; Le, Dang Quang Svend; Nielsen, Agnete Desirée; Nygaard, Jens Vinge; Bünger, Cody Erik; Lind, Martin

    2012-06-01

    To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide) scaffold. By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water-dioxane-PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT-PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O'Driscoll score. In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells. The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide scaffold with cells.

  15. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

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    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  16. Optimal construction and delivery of dual-functioning lentiviral vectors for type I collagen-suppressed chondrogenesis in synovium-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Feng; Yao, Yongchang; Zhou, Ruijie; Su, Kai; Citra, Fudiman; Wang, Dong-An

    2011-06-01

    This study aims to deliver both transforming growth factor β3 (TGF-β3) and shRNA targeting type I collagen (Col I) by optimal construction and application of various dual-functioning lentiviral vectors to induce Col I-suppressed chondrogenesis in synovium-derived mesenchymal stem cells (SMSCs). We constructed four lentiviral vectors (LV-1, LV-2, LV-3 and LV-4) with various arrangements of the two expression cassettes in different positions and orientations. Col I inhibition efficiency and chondrogenic markers were assessed with qPCR, ELISA and staining techniques. Among the four vectors, LV-1 has two distant and reversely oriented cassettes, LV-2 has two distant and same-oriented cassettes, LV-3 has two proximal and reversely oriented cassettes, and LV-4 has two proximal and same-oriented cassettes. Col I and chondrogenic markers, including type II collagen (Col II), aggrecan and glycosaminoglycan (GAG), were examined in SMSCs cultured in 3-D alginate hydrogel. All of the four vectors showed distinct effects in Col I level as well as diverse inductive efficiencies in upregulation of the cartilaginous markers. Based on real-time PCR results, LV-1 was optimal towards Col I-suppressed chondrogenesis. LV-1 vector is competent to promote Col I-suppressed chondrogenesis in SMSCs.

  17. Formalizing and proving a typing result for security protocols in Isabelle/HOL

    DEFF Research Database (Denmark)

    Hess, Andreas Viktor; Modersheim, Sebastian

    2017-01-01

    or the positive output of a verification tool. However several of these works have used a typed model, where the intruder is restricted to "well-typed" attacks. There also have been several works that show that this is actually not a restriction for a large class of protocols, but all these results so far...... are again pen-and-paper proofs. In this work we present a formalization of such a typing result in Isabelle/HOL. We formalize a constraint-based approach that is used in the proof argument of such typing results, and prove its soundness, completeness and termination. We then formalize and prove the typing...... result itself in Isabelle. Finally, to illustrate the real-world feasibility, we prove that the standard Transport Layer Security (TLS) handshake satisfies the main condition of the typing result....

  18. Extracellular matrix fragmentation in young, healthy cartilaginous tissues.

    Science.gov (United States)

    Craddock, R J; Hodson, N W; Ozols, M; Shearer, T; Hoyland, J A; Sherratt, M J

    2018-02-09

    Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC) and the nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact aggrecan ( containing three globular domains) is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months), bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 %) were fragmented (lacking one or more globular domains). Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa) comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis). As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2) as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2), it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally) and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

  19. Presic-Boyd-Wong Type Results in Ordered Metric Spaces

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    Satish Shukla

    2014-04-01

    Full Text Available The purpose of this paper is to prove some Presic-Boyd-Wong type fixed point theorems in ordered metric spaces. The results of this paper generalize the famous results of Presic and Boyd-Wong in ordered metric spaces. We also initiate the homotopy result in product spaces. Some examples are provided which illustrate the results proved herein.

  20. In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation

    DEFF Research Database (Denmark)

    Kubosch, Eva Johanna; Heidt, Emanuel; Niemeyer, Philipp

    2017-01-01

    Purpose: The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources. Methods: Via clinically validated flow cytometry...... analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC). Results: Primary...

  1. Extracellular matrix fragmentation in young, healthy cartilaginous tissues

    Directory of Open Access Journals (Sweden)

    RJ Craddock

    2018-02-01

    Full Text Available Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC and the nucleus pulposus (NP of the intervertebral disc (IVD. Whilst structural heterogeneity of intact aggrecan ( containing three globular domains is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months, bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 % were fragmented (lacking one or more globular domains. Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p < 0.0001. In contrast, fibrillar collagen appeared structurally intact and tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis. As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2 as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2, it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

  2. The effect of protease inhibitors on the induction of osteoarthritis-related biomarkers in bovine full-depth cartilage explants

    DEFF Research Database (Denmark)

    He, Yi; Zheng, Qinlong; Jiang, Mengmeng

    2015-01-01

    contribution of ADAMTS-4 and ADAMTS-5 to cartilage degradation upon catabolic stimulation; ii) To investigate the effect of regulating the activities of key enzymes by mean of broad-spectrum inhibitors. Methods Bovine full-depth cartilage explants stimulated with tumor necrosis factor alpha (TNF...... protease for the generation of 374ARGS aggrecan fragment in the TNF-α/OSM stimulated bovine cartilage explants. This study addresses the need to determine the roles of ADAMTS-4 and ADAMTS-5 in human articular degradation in OA and hence identify the attractive target for slowing down human cartilage......Objective The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative...

  3. Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

    Directory of Open Access Journals (Sweden)

    Baichuan Wang

    2014-01-01

    Full Text Available Designer self-assembling peptide nanofiber hydrogel scaffolds have been considered as promising biomaterials for tissue engineering because of their excellent biocompatibility and biofunctionality. Our previous studies have shown that a novel designer functionalized self-assembling peptide nanofiber hydrogel scaffold (RLN/RADA16, LN-NS containing N-terminal peptide sequence of link protein (link N can promote nucleus pulposus cells (NPCs adhesion and three-dimensional (3D migration and stimulate biosynthesis of type II collagen and aggrecan by NPCs in vitro. The present study has extended these investigations to determine the effects of this functionalized LN-NS on bone marrow stem cells (BMSCs, a potential cell source for NP regeneration. Although the functionalized LN-NS cannot promote BMSCs proliferation, it significantly promotes BMSCs adhesion compared with that of the pure RADA16 hydrogel scaffold. Moreover, the functionalized LN-NS remarkably stimulates biosynthesis and deposition of type II collagen and aggrecan. These data demonstrate that the functionalized peptide nanofiber hydrogel scaffold containing link N peptide as a potential matrix substrate will be very useful in the NP tissue regeneration.

  4. Structural Variation of Chondroitin Sulfate Chains Contributes to the Molecular Heterogeneity of Perineuronal Nets

    Directory of Open Access Journals (Sweden)

    Shinji Miyata

    2018-02-01

    Full Text Available Aggrecan, a chondroitin sulfate (CS proteoglycan, forms lattice-like extracellular matrix structures called perineuronal nets (PNNs. Neocortical PNNs primarily ensheath parvalbumin-expressing inhibitory neurons (parvalbumin, PV cells late in brain development. Emerging evidence indicates that PNNs promote the maturation of PV cells by enhancing the incorporation of homeobox protein Otx2 and regulating experience-dependent neural plasticity. Wisteria floribunda agglutinin (WFA, an N-acetylgalactosamine-specific plant lectin, binds to the CS chains of aggrecan and has been widely used to visualize PNNs. Although PNNs show substantial molecular heterogeneity, the importance of this heterogeneity in neural plasticity remains unknown. Here, in addition to WFA lectin, we used the two monoclonal antibodies Cat315 and Cat316, both of which recognize the glycan structures of aggrecan, to investigate the molecular heterogeneity of PNNs. WFA detected the highest number of PNNs in all cortical layers, whereas Cat315 and Cat316 labeled only a subset of PNNs. WFA+, Cat315+, and Cat316+ PNNs showed different laminar distributions in the adult visual cortex. WFA, Cat315 and Cat316 detected distinct, but partially overlapping, populations of PNNs. Based on the reactivities of these probes, we categorized PNNs into four groups. We found that two subpopulation of PNNs, one with higher and one with lower WFA-staining are differentially labeled by Cat316 and Cat315, respectively. CS chains recognized by Cat316 were diminished in mice deficient in an enzyme involved in the initiation of CS-biosynthesis. Furthermore, WFA+ and Cat316+ aggrecan were spatially segregated and formed microdomains in a single PNN. Otx2 co-localized with Cat316+ but not with WFA+ aggrecan in PNNs. Our results suggest that the heterogeneity of PNNs around PV cells may affect the functional maturation of these cells.

  5. Differentiation of stem cells from human infrapatellar fat pad: characterization of cells undergoing chondrogenesis.

    Science.gov (United States)

    Felimban, Raed; Ye, Ken; Traianedes, Kathy; Di Bella, Claudia; Crook, Jeremy; Wallace, Gordon G; Quigley, Anita; Choong, Peter F M; Myers, Damian E

    2014-08-01

    Hyaline cartilage repair is a significant challenge in orthopedics and current techniques result in formation of fibrocartilage. Human infrapatellar fat pad (hIPFP)-derived mesenchymal stem cells (MSCs) are capable of differentiation into multiple tissue lineages, including cartilage and bone. Chondrogenesis is a crucial part of normal skeletal development but the molecular mechanisms are yet to be completely defined. In this study we sourced hIPFP-derived MSCs utilizing chondrogenic growth factors, transforming growth factor beta-3, and bone morphogenetic protein-6, to form hyaline-like cartilage in micromass cultures and we studied chondrogenic development of 7, 14, and 28 days. The purpose of this study was (1) to characterize chondrogenesis from MSCs derived from hIPFP tissue by conventional techniques and (2) to characterize temporal changes of key molecular components during chondrogenesis using microarray gene expression. Endpoints included histology, immunohistochemistry (IHC), gene expression profiles using a microarray technique, and changes in expression of specific genes using quantitative real-time polymerase chain reaction. Over 14-28 days, clusters of encapsulated chondrocytes formed surrounded by collagen type II and aggrecan in the extracellular matrix (ECM). Collagen type II and aggrecan production was confirmed using IHC and chondrogenic lineage markers were studied; SRY-related transcription factor (SOX9), collagen type II alpha 1 (COL2A1), and aggrecan gene expression increased significantly over the time course. Normalized microarray highlighted 608 differentially expressed genes; 10 chondrogenic genes were upregulated (2- to 87-fold), including COL2A1, COL10A1, COL9A1, COL11A1, COL9A2, COL11A2, COL1A1, COMP, SOX9, and COL3A1. We found that the upregulated genes (twofold or greater) represent significant level of expression (enrichment score) for the ECM structural constituent of the molecular functional at days 7, 14, and 28 during

  6. Comparison of fluoroscopy-guided pull-type percutaneous radiological gastrostomy (pull-type-PRG) with conventional percutaneous radiological gastrostomy (push-type-PRG): clinical results in 253 patients

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yang; Schneider, J.; Dueber, C.; Pitton, M.B. [University Medical Center of the Johannes Gutenberg University Mainz, Department of Diagnostic and Interventional Radiology, Mainz (Germany)

    2011-11-15

    To analyze the clinical results and complications of fluoroscopy guided internal-external pull-type percutaneous radiological gastrostomy (pull-type-PRG) and conventional external-internal percutaneous radiological gastrostomy (push-type-PRG). A total of 253 patients underwent radiological gastrostomy between January 2002 and January 2010. Data were collected retrospectively from radiology reports, Chart review of clinical notes, procedure reports, discharge summaries and subsequent hospital visits. Statistical analysis was performed to compare the two methods for gastrostomy with respect to peri-interventional aspects and clinical results. 128 patients received the Pull-type-PRG whereas the other 125 patients were served with the Push-type-PRG. Indications for gastrostomy were similar in these two groups. The most frequent indications for the both methods were stenotic oesophageal tumors or head/neck tumors (54.7% in pull-type-PRG, 68% in push-type-PRG). Gastrostomy procedures were successful in 98.3% in pull-type-PRG compared to 92% in push-type-PRG. There was no procedure-related mortality. Compared to Push-type-PRG, the peri-interventional complication rate was significantly reduced in pull-type-PRG (14.8% versus 34.4%, P = 0.002). Compared to the external-internal push-type-PRG, the internal-external Pull-type-PRG showed a high primary success rate and a decreased incidence of peri-interventional complications. (orig.)

  7. Comparison of fluoroscopy-guided pull-type percutaneous radiological gastrostomy (pull-type-PRG) with conventional percutaneous radiological gastrostomy (push-type-PRG): clinical results in 253 patients

    International Nuclear Information System (INIS)

    Yang, Yang; Schneider, J.; Dueber, C.; Pitton, M.B.

    2011-01-01

    To analyze the clinical results and complications of fluoroscopy guided internal-external pull-type percutaneous radiological gastrostomy (pull-type-PRG) and conventional external-internal percutaneous radiological gastrostomy (push-type-PRG). A total of 253 patients underwent radiological gastrostomy between January 2002 and January 2010. Data were collected retrospectively from radiology reports, Chart review of clinical notes, procedure reports, discharge summaries and subsequent hospital visits. Statistical analysis was performed to compare the two methods for gastrostomy with respect to peri-interventional aspects and clinical results. 128 patients received the Pull-type-PRG whereas the other 125 patients were served with the Push-type-PRG. Indications for gastrostomy were similar in these two groups. The most frequent indications for the both methods were stenotic oesophageal tumors or head/neck tumors (54.7% in pull-type-PRG, 68% in push-type-PRG). Gastrostomy procedures were successful in 98.3% in pull-type-PRG compared to 92% in push-type-PRG. There was no procedure-related mortality. Compared to Push-type-PRG, the peri-interventional complication rate was significantly reduced in pull-type-PRG (14.8% versus 34.4%, P = 0.002). Compared to the external-internal push-type-PRG, the internal-external Pull-type-PRG showed a high primary success rate and a decreased incidence of peri-interventional complications. (orig.)

  8. Attachment sites of the coracoclavicular ligaments are characterized by fibrocartilage differentiation: a study on human cadaveric tissue.

    Science.gov (United States)

    Ockert, B; Braunstein, V; Sprecher, C; Shinohara, Y; Kirchhoff, C; Milz, S

    2012-02-01

    We analyzed the immunohistochemical labeling patterns of the extracellular matrix of the coracoclavicular ligaments (CCL) in order to relate the molecular composition of the attachment sites to their mechanical environment. Ligaments were exposed from 12 fresh-frozen human cadaveric samples (four males, mean age: 48.6 ± 12.1 years). Cryosection of methanol-fixed and decalcified tissue was cut and sections were labeled with a panel of monoclonal antibodies directed against collagens, proteoglycans and proteins of vascular components. Attachment sites of both ligaments showed characteristic fibrocartilaginous labeling of collagen type II, aggrecan and link protein in all samples. Labeling for type II collagen was most conspicuous at the insertion of the coracoid process. Morphometry of adjacent samples revealed a fibrocartilage zone of 10-15% in relationship with the ligament proper, where labeling for type II collagen, aggrecan and link protein was negative. The presence of fibrocartilage at both entheses of the trapezoid and conoid ligament suggests that the CCL complex is subject to shear/compression forces. A variable fibrocartilage differentiation at the entheses of both ligaments may be related to the marked change in loading and insertion angle that the ligaments undergo during shoulder movement. © 2010 John Wiley & Sons A/S.

  9. Semiquantitative analysis of ECM molecules in the different cartilage layers in early and advanced osteoarthritis of the knee joint.

    Science.gov (United States)

    Lahm, Andreas; Kasch, Richard; Mrosek, Eike; Spank, Heiko; Erggelet, Christoph; Esser, Jan; Merk, Harry

    2012-05-01

    The study was conducted to examine the expression of collagen type I and II in the different cartilage layers in relation to other ECM molecules during the progression of early osteoarthritic degeneration in human articular cartilage (AC). Quantitative real-time (RT)-PCR and colorimetrical techniques were used for calibration of Photoshop-based image analysis in detecting such lesions. Immunohistochemistry and histology were performed with 40 cartilage tissue samples showing mild (ICRS grade 1b) respectively moderate/advanced (ICRS grade 3a or 3b) (20 each) osteoarthritis compared with 15 healthy biopsies. Furthermore, we quantified our results on the gene expression of collagen type I and II and aggrecan with the help of real-time (RT)-PCR. Proteoglycan content was measured colorimetrically. The digitized images of histology and immunohistochemistry stains were analyzed with Photoshop software. T-test and Spearman correlation analysis were used for statistical analysis. In the earliest stages of AC deterioration the loss of collagen type II was associated with the appearance of collagen type I, shown by increasing amounts of collagen type I mRNA. During subsequent stages, a progressive loss of structural integrity was associated with increasing deposition of collagen type I as part of a natural healing response. A decrease of collagen type II is visible especially in the upper fibrillated area of the advanced osteoarthritic samples, which then leads to an overall decrease. Analysis of proteoglycan showed losses of the overall content and a loss of the classical zonal formation. Correlation analysis of the proteoglycan Photoshop measurements with the RT-PCR revealed strong correlation for Safranin O and collagen type I, medium for collagen type II, alcian blue and glycoprotein but weak correlation with PCR aggrecan results. Photoshop based image analysis might become a valuable supplement for well known histopathological grading systems of lesioned articular

  10. Effect of Human Serum and 2 Different Types of Platelet Concentrates on Human Meniscus Cell Migration, Proliferation, and Matrix Formation.

    Science.gov (United States)

    Freymann, Undine; Metzlaff, Sebastian; Krüger, Jan-Philipp; Hirsh, Glen; Endres, Michaela; Petersen, Wolf; Kaps, Christian

    2016-06-01

    To evaluate the effect of 10% human serum (HS), 5% platelet-rich plasma (PRP), and 5% autologous conditioned plasma (ACP) on migration, proliferation, and extracellular matrix (ECM) synthesis of human meniscus cells. Cell migration and proliferation on stimulation with HS, PRP, and ACP were assessed by chemotaxis assays and measurement of genomic DNA content. Meniscus cells were cultivated in pellets stimulated with 10% HS, 5% PRP, or 5% ACP. Meniscal ECM formation was evaluated by histochemical staining of collagen type I, type II, and proteoglycans and by analysis of fibrochondrocyte marker gene expression. Human meniscus cells were significantly attracted by all 3 blood-derived products (10% HS and 5% ACP: P = .0001, 5% PRP: P = .0002). Cell proliferation at day 9 was significantly increased on stimulation with 10% HS (P = .0001) and 5% PRP (P = .0002) compared with 5% ACP and controls. Meniscus cell pellet cultures showed the formation of a well-structured meniscal ECM with deposition of collagen type I, type II, and proteoglycans on stimulation with 10% HS, whereas 5% PRP or 5% ACP resulted in the formation of an inhomogeneous and more fibrous ECM. Stimulation with 10% HS and 5% ACP showed a significant induction of fibrochondrocyte marker genes such as aggrecan (HS: P = .0002, ACP: P = .0147), cartilage oligomeric matrix protein (HS: P = .0002, ACP: P = .0005), and biglycan (HS: P = .0002, ACP: P = .0003), whereas PRP showed no inducing effect. Among all tested blood-derived products, only stimulation with HS showed the formation of a meniscal ECM as well as positive cell proliferating and migrating effects in vitro. Regarding a potential biological repair of nonvascular meniscus lesions, our results may point toward the use of HS as a beneficial augment in regenerative meniscus repair approaches. Our findings may suggest that HS might be a beneficial augment for meniscus repair. Copyright © 2016 Arthroscopy Association of North America. Published

  11. Chloride channels regulate chondrogenesis in chicken mandibular mesenchymal cells.

    Science.gov (United States)

    Tian, Meiyu; Duan, Yinzhong; Duan, Xiaohong

    2010-12-01

    Voltage gated chloride channels (ClCs) play an important role in the regulation of intracellular pH and cell volume homeostasis. Mutations of these genes result in genetic diseases with abnormal bone deformation and body size, indicating that ClCs may have a role in chondrogenesis. In the present study, we isolated chicken mandibular mesenchymal cells (CMMC) from Hamburg-Hamilton (HH) stage 26 chick embryos and induced chondrocyte maturation by using ascorbic acid and β-glycerophosphate (AA-BGP). We also determined the effect of the chloride channel inhibitor NPPB [5-nitro-2-(3-phenylpropylamino) benzoic acid] on regulation of growth, differentiation, and gene expression in these cells using MTT and real-time PCR assays. We found that CLCN1 and CLCN3-7 mRNA were expressed in CMMC and NPPB reduced expression of CLCN3, CLCN5, and CLCN7 mRNA in these cells. At the same time, NPPB inhibited the growth of the CMMC, but had no effect on the mRNA level of cyclin D1 and cyclin E (P>0.05) with/without AA-BGP treatment. AA-BGP increased markers for early chondrocyte differentiation including type II collagen, aggrecan (Ptype X collagen. NPPB antagonized AA-BGP-induced expression of type II collagen and aggrecan (Ptype X collagen (PType X collagen might function as a target of chloride channel inhibitors during the differentiation process. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Coupling forces resulting from the type of chain saw used

    Directory of Open Access Journals (Sweden)

    Jolanta Malinowska-Borowska

    2014-03-01

    Full Text Available Introduction. Woodcutters’ working conditions are difficult due to the presence of numerous occupational hazards. Petrol –fuelled chain saws commonly used in forestry produce vibration, which may lead to the development of non-specific disorders in the upper extremities of the chain saw operator, referred to as hand-arm vibration syndrome (HAVS. The magnitude of coupling forces exerted on a vibrating tool handle may affect the severity of HAVS and hand-wrist cumulative trauma disorders. The aim of the presented study was to measure coupling forces exerted by fellers on various chain saws and to find correlation between force magnitude and type of tool used. Material and methods. Coupling forces applied by workers on different types of chain saws were measured by means of a hydro-electronic force meter. All measurements were carried out during the harvesting of wood in real work conditions. Results. Mean force applied by forestry workers on their tools was 44.2 N. Coupling forces registered during cutting wood with small universal chain saws were larger than forces exerted on models characterized by higher power profile. Forces applied on comparable tools produced by various manufacturers also differed. Conclusions. The relationship between coupling forces and power of the chain saw should lead to ergonomic improvements of the tool and vibration-reducing devices. These results can also be used as a recommendation for fellers in a range of using proper machines for different types of cut or types of wood. They may also be applicable to develop more effective methods for assessing vibration exposure risks among woodcutters.

  13. Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated from normal human and osteoarthritis patients.

    Science.gov (United States)

    Ying, Xiaozhou; Cheng, Shaowen; Shen, Yue; Cheng, Xiaojie; An Rompis, Ferdinand; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Peng, Lei; Tian, Xin Qiao; Lu, Chuan Zhu

    2012-01-01

    The aims of the study were to show the direct effect of nicotine with different concentrations (0, 25, 50, and 100 ng/ml) on chondrocytes isolated from normal human and osteoarthritis patients, respectively. Microscopic observation was performed during the culture with an inverted microscope. Methyl thiazolyl tetrazolium (MTT) assay method was adopted to observe the influence of nicotine on the proliferation of chondrocytes, and real-time PCR and ELISA were used to assay the mRNA and protein expression of type II collagen and aggrecan, respectively. We discovered that the OA chondrocytes were similar to fibroblasts in shape and grow slower than normal chondrocytes. The proliferation of the two kinds of chondrocytes was increased in a concentration-dependent manner and in a time-dependent manner (P<0.05). Also, we found that the mRNA level of type II collagen were upregulated under 25-100 ng/ml nicotine doses both in the two kinds of chondrocytes compared with control. The expression of protein levels of type II collagen were synthesized in line with the increase in mRNA. No effect was observed on aggrecan synthesis with any nicotine dose. We concluded that nicotine has the same effect on both chondrocytes, obtained either from osteoarthritis patients or from normal human, and the positive effect of smoking in OA may relate to the alteration in metabolism of chondrocytes.

  14. Chondroprotective Effects of Ginsenoside Rg1 in  Human Osteoarthritis Chondrocytes and a Rat Model  of Anterior Cruciate Ligament Transection

    Directory of Open Access Journals (Sweden)

    Wendan Cheng

    2017-03-01

    Full Text Available This study aimed to assess whether Ginsenoside Rg1 (Rg1 inhibits inflammatory responses in human chondrocytes and reduces articular cartilage damage in a rat model of osteoarthritis (OA. Gene expression and protein levels of type II collagen, aggrecan, matrix metalloproteinase (MMP‐13 and cyclooxygenase‐2 (COX‐2 were determined in vitro by quantitative real‐time‐polymerase chain reaction and Western blotting. Prostaglandin E2 (PGE2 amounts in the culture medium were determined by enzyme‐linked immunosorbent assay (ELISA. For in vivo assessment, a rat model of OA was generated by anterior cruciate ligament transection (ACLT. Four weeks after ACLT, Rg1 (30 or 60 mg/kg or saline was administered by gavage once a day for eight consecutive weeks. Joint damage was analyzed by histology and immunohistochemistry. Ginsenoside Rg1 inhibited Interleukin (IL‐1β‐induced chondrocyte gene and protein expressions of MMP‐13, COX‐2 and PGE2, and prevented type II collagen and aggrecan degradation, in a dose‐dependent manner. Administration of Ginsenoside Rg1 to OA rats attenuated cartilage degeneration, and reduced type II collagen loss and MMP‐13 levels. These findings demonstrated that Ginsenoside Rg1 can inhibit inflammatory responses in human chondrocytes in vitro and reduce articular cartilage damage in vivo, confirming the potential therapeutic value of Ginsenoside Rg1 in OA.

  15. Matrilin-3 Chondrodysplasia Mutations Cause Attenuated Chondrogenesis, Premature Hypertrophy and Aberrant Response to TGF-β in Chondroprogenitor Cells

    OpenAIRE

    Chathuraka T. Jayasuriya; Fiona H. Zhou; Ming Pei; Zhengke Wang; Nicholas J. Lemme; Paul Haines; Qian Chen

    2014-01-01

    Studies have shown that mutations in the matrilin-3 gene (MATN3) are associated with multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT) MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in c...

  16. Integration of molecular typing results into tuberculosis surveillance in Germany—A pilot study

    Science.gov (United States)

    Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

    2017-01-01

    An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48–98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the communication between local public health offices in different counties to enhance TB control

  17. Integration of molecular typing results into tuberculosis surveillance in Germany-A pilot study.

    Science.gov (United States)

    Andrés, Marta; Göhring-Zwacka, Elke; Fiebig, Lena; Priwitzer, Martin; Richter, Elvira; Rüsch-Gerdes, Sabine; Haas, Walter; Niemann, Stefan; Brodhun, Bonita

    2017-01-01

    An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age Germany (OR = 2.01, 95% CI: 1.44-2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48-98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the

  18. Initial results from 3D-DDTC detectors on p-type substrates

    Energy Technology Data Exchange (ETDEWEB)

    Zoboli, A., E-mail: zoboli@disi.unitn.i [Dipartimento di Ingegneria e Scienza dell' Informazione, Universita di Trento, and INFN, Sezione di Padova (Gruppo Collegato di Trento), Via Sommarive, 14, I-38100 Povo di Trento (Italy); Boscardin, M. [Fondazione Bruno Kessler, Centro per i Materiali e i Microsistemi, Via Sommarive, 18, I-38100 Povo di Trento (Italy); Bosisio, L. [Dipartimento di Fisica, Universita di Trieste, and INFN, Sezione di Trieste, Via A. Valerio, 2, I-34127 Trieste (Italy); Dalla Betta, G.-F. [Dipartimento di Ingegneria e Scienza dell' Informazione, Universita di Trento, and INFN, Sezione di Padova (Gruppo Collegato di Trento), Via Sommarive, 14, I-38100 Povo di Trento (Italy); Piemonte, C.; Ronchin, S.; Zorzi, N. [Fondazione Bruno Kessler, Centro per i Materiali e i Microsistemi, Via Sommarive, 18, I-38100 Povo di Trento (Italy)

    2010-01-11

    Owing to their superior radiation hardness compared to planar detectors, 3D detectors are one of the most promising technologies for the LHC upgrade foreseen in 2017. Fondazione Bruno Kessler has developed 3D Double-side Double-Type Column (3D-DDTC) detectors providing a technological simplifications with respect to a standard 3D process while aiming at comparable detector performance. We present selected results from the electrical characterization of 3D-DDTC structures from the second batch made on p-type substrates, supported also by TCAD simulations.

  19. Nuclear deformation and expression change of cartilaginous genes during in vitro expansion of chondrocytes

    International Nuclear Information System (INIS)

    Hoshiba, Takashi; Yamada, Tomoe; Lu, Hongxu; Kawazoe, Naoki; Tateishi, Tetsuya; Chen, Guoping

    2008-01-01

    Cartilaginous gene expression decreased when chondrocytes were expanded on cell-culture plates. Understanding the dedifferentiation mechanism may provide valuable insight into cartilage tissue engineering. Here, we demonstrated the relationship between the nuclear shape and gene expression during in vitro expansion culture of chondrocytes. Specifically, the projected nuclear area increased and cartilaginous gene expressions decreased during in vitro expansion culture. When the nuclear deformation was recovered by cytochalasin D treatment, aggrecan expression was up-regulated and type I collagen (Col1a2) expression was down-regulated. These results suggest that nuclear deformation may be one of the mechanisms for chondrocyte dedifferentiation during in vitro expansion culture

  20. Estrogen Enhances Matrix Synthesis in Nucleus Pulposus Cell through the Estrogen Receptor β-p38 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Pei Li

    2016-11-01

    Full Text Available Background/Aims: Matrix homeostasis within the disc nucleus pulposus (NP tissue is important for disc function. Increasing evidence indicates that sex hormone can influence the severity of disc degeneration. This study was aimed to study the role of 17β-estradiol (E2 in NP matrix synthesis and its underlying mechanism. Methods: Rat NP cells were cultured with (10-5, 10-7 and 10-9 M or without (control E2 for48 hours. The estrogen receptor (ER-β antagonist PHTPP and ERβ agonist ERB 041 were used to investigate the role mediated by ERβ. The p38 MAPK inhibitor SB203580 was used to investigate the role of p38 MAPK signaling pathway. Gene and protein expression of SOX9, aggrecan and collagen II, glycosaminoglycan (GAG content, and immunostaining assay for aggrecan and collagen II were analyzed to evaluate matrix production in rat NP cells. Results: E2 enhanced NP matrix synthesis in a concentration-dependent manner regarding gene and proetin expression of SOX9, aggrecan and collagen II, protein deposition of aggrecan and collagen II, and GAG content. Moreover, activation of p38 MAPK signaling pathway was increased with elevating E2 concentration. Further analysis indicated that ERB 041 and PHTPP could respectively enhance and suppress effects of E2 on matrix synthesis in NP cells, as well as activation of p38 MAPK pathway. Additionally, inhibition of p38 MAPK signaling pathway significantly abolished the effects of E2 on matrix synthesis. Conclusion: E2 can enhance matrix synthesis of NP cells and the ERβ/p38 MAPK pathway is involved in this regulatory process.

  1. Mangiferin Reduces the Inhibition of Chondrogenic Differentiation by IL-1β in Mesenchymal Stem Cells from Subchondral Bone and Targets Multiple Aspects of the Smad and SOX9 Pathways

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2014-09-01

    Full Text Available Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1β-stimulated mesenchymal stem cells (MSCs from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1β (IL-1β. Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF-β, bone morphogenetic protein (BMP-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y–box (SRY-box containing gene 9 (SOX9, type 2α1 collagen (Col2α1, cartilage link protein, and aggrecan. In IL-1β-stimulated MSCs, mangiferin significantly reversed the production of TGF-β, BMP-2, BMP-4, SOX9, Col2α1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5. Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1β-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2α1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways.

  2. Disordered glycometabolism involved in pathogenesis of Kashin–Beck disease, an endemic osteoarthritis in China

    International Nuclear Information System (INIS)

    Wu, Cuiyan; Lei, Ronghui; Tiainen, Mika; Wu, Shixun; Zhang, Qiang; Pei, Fuxing; Guo, Xiong

    2014-01-01

    Kashin–Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ( 1 H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC–PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD. - Highlights: • Disordered glycometabolism in KBD was demonstrated by combining serum metabolomics and chondrocyte studies. • Glucose and TNF-α were key molecules linked to altered metabolism and inflammation in the pathophysiology of KBD. • The glycometabolism disorder was linked to expression of type II collagen and aggrecan, ROS and apoptosis of KBD chondrocytes

  3. Anti-inflammatory and anti-osteoarthritis effects of tectorigenin

    Directory of Open Access Journals (Sweden)

    Cheng-Long Wang

    2017-08-01

    Full Text Available Osteoarthritis (OA is a common and dynamic disease of the joints, including the articular cartilage, underlying bones and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec is known to affect many biological processes; however, its effects on articular chondrocytes remain unclear. This study aimed to assess the effects of Tec on articular cartilage. In vitro, Tec inhibited the expression levels of type X collagen, cyclooxigenase-2, matrix metalloproteinase (MMP-3 and MMP-13, but enhanced the expression of Runx1, type II collagen and aggrecan in the presence of IL-1β. Meanwhile, Tec inhibited apoptosis through the Bax/Bcl-2/caspase-3 pathway, upregulating p-Bad, downregulating the Bax/Bcl-2 ratio, and activating caspase-3 compared with IL-1β treatment only. Moreover, this process was partially regulated by NF-κB P65. In vivo, the chondroprotective effects of Tec were assessed by establishing a model of surgically induced OA. Tec-treated joints exhibited fewer osteoarthritic changes than saline-treated joints. Meanwhile, 1.5 μg/kg Tec treatment produced a greater protective effect than 0.75 μg/kg Tec. The Osteoarthritis Research Society International (OARSI scoring system, employed to assess histopathological grading of the models, as well immunohistochemistry for Aggrecan Neoepitope and MMP-3, further confirmed the results. In conclusion, this study showed that Tec plays a chondroprotective role in the OA process by preventing articular cartilage degeneration and chondrocyte apoptosis via the NF-κB P65 pathway.

  4. Disordered glycometabolism involved in pathogenesis of Kashin–Beck disease, an endemic osteoarthritis in China

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cuiyan, E-mail: xj.cy.69@stu.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Lei, Ronghui, E-mail: leirh@mail.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Tiainen, Mika, E-mail: mika.tiainen@uef.fi [School of Pharmacy, University of Eastern Finland, Kuopio (Finland); Wu, Shixun, E-mail: wushixun313@stu.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China); Zhang, Qiang, E-mail: wdrr@163.com [Department of Kashin–Beck Disease, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai 811602 (China); Pei, Fuxing, E-mail: peifuxing@vip.163.com [Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041 (China); Guo, Xiong, E-mail: guox@mail.xjtu.edu.cn [School of Public Health, Health Science Centre of Xi' an Jiaotong University, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education (China); Key Laboratory of Trace elements and Endemic Diseases, Ministry of Health, Xi' an, Shaanxi 710061 (China)

    2014-08-15

    Kashin–Beck disease (KBD) is a chronic endemic osteoarthritis in China. Previous studies have suggested a role of metabolic dysfunction in causation of this disease. In this investigation, the metabolomics approach and cell experiments were used to discover the metabolic changes and their effects on KBD chondrocytes. Nuclear magnetic resonance ({sup 1}H NMR) spectroscopy was used to examine serum samples from both the KBD patients and normal controls. The pattern recognition multivariate analysis (OSC–PLS) and quantitative analysis (QMTLS iterator) revealed altered glycometabolism in KBD, with increased glucose and decreased lactate and citrate levels. IPA biological analysis showed the centric location of glucose in the metabolic network. Massive glycogen deposits in chondrocytes and increased uptake of glucose by chondrocytes further confirmed disordered glycometabolism in KBD. An in vitro study showed the effects of disordered glycometabolism in chondrocytes. When chondrocytes were treated with high glucose, expression of type II collagen and aggrecan were decreased, while TNF-α expression, the level of cellular reactive oxygen species and cell apoptosis rates all were increased. Therefore, our results demonstrated that disordered glycometabolism in patients with KBD was linked to the damage of chondrocytes. This may provide a new basis for understanding the pathogenesis of KBD. - Highlights: • Disordered glycometabolism in KBD was demonstrated by combining serum metabolomics and chondrocyte studies. • Glucose and TNF-α were key molecules linked to altered metabolism and inflammation in the pathophysiology of KBD. • The glycometabolism disorder was linked to expression of type II collagen and aggrecan, ROS and apoptosis of KBD chondrocytes.

  5. Comparison results on preconditioned SOR-type iterative method for Z-matrices linear systems

    Science.gov (United States)

    Wang, Xue-Zhong; Huang, Ting-Zhu; Fu, Ying-Ding

    2007-09-01

    In this paper, we present some comparison theorems on preconditioned iterative method for solving Z-matrices linear systems, Comparison results show that the rate of convergence of the Gauss-Seidel-type method is faster than the rate of convergence of the SOR-type iterative method.

  6. Perineuronal Nets in Spinal Motoneurones: Chondroitin Sulphate Proteoglycan around Alpha Motoneurones

    Directory of Open Access Journals (Sweden)

    Sian F. Irvine

    2018-04-01

    Full Text Available Perineuronal nets (PNNs are extracellular matrix structures surrounding neuronal sub-populations throughout the central nervous system, regulating plasticity. Enzymatically removing PNNs successfully enhances plasticity and thus functional recovery, particularly in spinal cord injury models. While PNNs within various brain regions are well studied, much of the composition and associated populations in the spinal cord is yet unknown. We aim to investigate the populations of PNN neurones involved in this functional motor recovery. Immunohistochemistry for choline acetyltransferase (labelling motoneurones, PNNs using Wisteria floribunda agglutinin (WFA and chondroitin sulphate proteoglycans (CSPGs, including aggrecan, was performed to characterise the molecular heterogeneity of PNNs in rat spinal motoneurones (Mns. CSPG-positive PNNs surrounded ~70–80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co-localised with WFA in the spinal Mns, while ~15–30% of Mns showed CSPG-positive but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90% of alpha Mns. The results indicate that (1 aggrecan labels spinal PNNs better than WFA, and (2 there are differences in PNN composition and their associated neuronal populations between the spinal cord and cortex. Insights into the role of PNNs and their molecular heterogeneity in the spinal motor pools could aid in designing targeted strategies to enhance functional recovery post-injury.

  7. Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

    Directory of Open Access Journals (Sweden)

    Hongsik Cho

    2015-01-01

    Full Text Available Patients with osteoarthritis (OA, a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs, and cyclooxygenase-2 (COX-2 selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM. To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2. The chondrocytes were then treated with either a steroid (prednisone, a nonspecific COX inhibitor NSAID (piroxicam, or a COX-2 selective NSAID (celecoxib. Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.

  8. Taurine Promotes the Cartilaginous Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Vitro.

    Science.gov (United States)

    Yao, Xiuhua; Huang, Huiling; Li, Zhou; Liu, Xiaohua; Fan, Weijia; Wang, Xinping; Sun, Xuelian; Zhu, Jianmin; Zhou, Hongrui; Wei, Huaying

    2017-08-01

    Taurine has been reported to influence osteogenic differentiation, but the role of taurine on cartilaginous differentiation using human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) remains unclear. In this study, we investigated the effect of taurine (0, 1, 5 and 10 mM) on the proliferation and chondrogenesis of hUC-MSCs by analyzing cell proliferation, accumulation of glycosaminoglycans and expression of cartilage specific mRNA. The results show though taurine did not affected the proliferation of hUC-MSCs, 5 mM of taurine is sufficient to enhanced the accumulation of glycosaminoglycans and up-regulate cartilage specific mRNA expression, namely collagen type II, aggrecan and SOX9. Taurine also inhibits chondrocyte dedifferentiation by reducing expression of collagen type I mRNA. Taken together, our study reveals that taurine promotes and maintains the chondrogenesis of hUC-MSCs.

  9. An evaluation of chondrocyte morphology and gene expression on superhydrophilic vertically-aligned multi-walled carbon nanotube films.

    Science.gov (United States)

    Antonioli, Eliane; Lobo, Anderson O; Ferretti, Mario; Cohen, Moisés; Marciano, Fernanda R; Corat, Evaldo J; Trava-Airoldi, Vladimir J

    2013-03-01

    Cartilage serves as a low-friction and wear-resistant articulating surface in diarthrodial joints and is also important during early stages of bone remodeling. Recently, regenerative cartilage research has focused on combinations of cells paired with scaffolds. Superhydrophilic vertically aligned carbon nanotubes (VACNTs) are of particular interest in regenerative medicine. The aim of this study is to evaluate cell expansion of human articular chondrocytes on superhydrophilic VACNTs, as well as their morphology and gene expression. VACNT films were produced using a microwave plasma chamber on Ti substrates and submitted to an O2 plasma treatment to make them superhydrophilic. Human chondrocytes were cultivated on superhydrophilic VACNTs up to five days. Quantitative RT-PCR was performed to measure type I and type II Collagen, Sox9, and Aggrecan mRNA expression levels. The morphology was analyzed by scanning electron microscopy (SEM) and confocal microscopy. SEM images demonstrated that superhydrophilic VACNTs permit cell growth and adhesion of human chondrocytes. The chondrocytes had an elongated morphology with some prolongations. Chondrocytes cultivated on superhydrophilic VACNTs maintain the level expression of Aggrecan, Sox9, and Collagen II determined by qPCR. This study was the first to indicate that superhydrophilic VACNTs may be used as an efficient scaffold for cartilage or bone repair. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes.

    Science.gov (United States)

    Salamanna, F; Frizziero, A; Pagani, S; Giavaresi, G; Curzi, D; Falcieri, E; Marini, M; Abruzzo, P M; Martini, L; Fini, M

    2015-02-01

    The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenocytes. Twenty-four male Sprague-Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1β, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1β was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.

  11. The Influence of IL-10 and TNFα on Chondrogenesis of Human Mesenchymal Stromal Cells in Three-Dimensional Cultures

    Directory of Open Access Journals (Sweden)

    Michal Jagielski

    2014-09-01

    Full Text Available Chondrogenic differentiated mesenchymal stromal cells (MSCs are a promising cell source for articular cartilage repair. This study was undertaken to determine the effectiveness of two three-dimensional (3D culture systems for chondrogenic MSC differentiation in comparison to primary chondrocytes and to assess the effect of Interleukin (IL-10 and Tumor Necrosis Factor (TNFα on chondrogenesis by MSCs in 3D high-density (H-D culture. MSCs were isolated from femur spongiosa, characterized using a set of typical markers and introduced in scaffold-free H-D cultures or non-woven polyglycolic acid (PGA scaffolds for chondrogenic differentiation. H-D cultures were stimulated with recombinant IL-10, TNFα, TNFα + IL-10 or remained untreated. Gene and protein expression of type II collagen, aggrecan, sox9 and TNFα were examined. MSCs expressed typical cell surface markers and revealed multipotency. Chondrogenic differentiated cells expressed cartilage-specific markers in both culture systems but to a lower extent when compared with articular chondrocytes. Chondrogenesis was more pronounced in PGA compared with H-D culture. IL-10 and/or TNFα did not impair the chondrogenic differentiation of MSCs. Moreover, in most of the investigated samples, despite not reaching significance level, IL-10 had a stimulatory effect on the type II collagen, aggrecan and TNFα expression when compared with the respective controls.

  12. The influence of IL-10 and TNFα on chondrogenesis of human mesenchymal stromal cells in three-dimensional cultures.

    Science.gov (United States)

    Jagielski, Michal; Wolf, Johannes; Marzahn, Ulrike; Völker, Anna; Lemke, Marion; Meier, Carola; Ertel, Wolfgang; Godkin, Owen; Arens, Stephan; Schulze-Tanzil, Gundula

    2014-09-09

    Chondrogenic differentiated mesenchymal stromal cells (MSCs) are a promising cell source for articular cartilage repair. This study was undertaken to determine the effectiveness of two three-dimensional (3D) culture systems for chondrogenic MSC differentiation in comparison to primary chondrocytes and to assess the effect of Interleukin (IL)-10 and Tumor Necrosis Factor (TNF)α on chondrogenesis by MSCs in 3D high-density (H-D) culture. MSCs were isolated from femur spongiosa, characterized using a set of typical markers and introduced in scaffold-free H-D cultures or non-woven polyglycolic acid (PGA) scaffolds for chondrogenic differentiation. H-D cultures were stimulated with recombinant IL-10, TNFα, TNFα + IL-10 or remained untreated. Gene and protein expression of type II collagen, aggrecan, sox9 and TNFα were examined. MSCs expressed typical cell surface markers and revealed multipotency. Chondrogenic differentiated cells expressed cartilage-specific markers in both culture systems but to a lower extent when compared with articular chondrocytes. Chondrogenesis was more pronounced in PGA compared with H-D culture. IL-10 and/or TNFα did not impair the chondrogenic differentiation of MSCs. Moreover, in most of the investigated samples, despite not reaching significance level, IL-10 had a stimulatory effect on the type II collagen, aggrecan and TNFα expression when compared with the respective controls.

  13. Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Sørensen, Inge Juul; Lambert, Robert G W

    2011-01-01

    To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix...... metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy....

  14. Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: A study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Sørensen, Inge Juul; Lambert, Robert G W

    2011-01-01

    To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix...... metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor a (TNFa) inhibitor therapy....

  15. Poly(γ-Glutamic Acid) as an Exogenous Promoter of Chondrogenic Differentiation of Human Mesenchymal Stem/Stromal Cells.

    Science.gov (United States)

    Antunes, Joana C; Tsaryk, Roman; Gonçalves, Raquel M; Pereira, Catarina Leite; Landes, Constantin; Brochhausen, Christoph; Ghanaati, Shahram; Barbosa, Mário A; Kirkpatrick, C James

    2015-06-01

    Cartilage damage and/or aging effects can cause constant pain, which limits the patient's quality of life. Although different strategies have been proposed to enhance the limited regenerative capacity of cartilage tissue, the full production of native and functional cartilaginous extracellular matrix (ECM) has not yet been achieved. Poly(γ-glutamic acid) (γ-PGA), a naturally occurring polyamino acid, biodegradable into glutamate residues, has been explored for tissue regeneration. In this work, γ-PGA's ability to support the production of cartilaginous ECM by human bone marrow mesenchymal stem/stromal cells (MSCs) and nasal chondrocytes (NCs) was investigated. MSC and NC pellets were cultured in basal medium (BM), chondrogenic medium (CM), and CM-γ-PGA-supplemented medium (CM+γ-PGA) over a period of 21 days. Pellet size/shape was monitored with time. At 14 and 21 days of culture, the presence of sulfated glycosaminoglycans (sGAGs), type II collagen (Col II), Sox-9, aggrecan, type XI collagen (Col XI), type X collagen (Col X), calcium deposits, and type I collagen (Col I) was analyzed. After excluding γ-PGA's cytotoxicity, earlier cell condensation, higher sGAG content, Col II, Sox-9 (day 14), aggrecan, and Col X (day 14) production was observed in γ-PGA-supplemented MSC cultures, with no signs of mineralization or Col I. These effects were not evident with NCs. However, Sox-9 (at day 14) and Col X (at days 14 and 21) were increased, decreased, or absent, respectively. Overall, γ-PGA improved chondrogenic differentiation of MSCs, increasing ECM production earlier in culture. It is proposed that γ-PGA incorporation in novel biomaterials has a beneficial impact on future approaches for cartilage regeneration.

  16. Results of noise analysis in the WWER 440 - type nuclear power plant Dukovany

    International Nuclear Information System (INIS)

    Runkel, J.; Stegemann, D.; Fiedler, J.; Hrosso, P.; Figedy, S.; Sadilek, J.; Hulin, J.

    1996-01-01

    Results of a common work in the frame of scientific and technological cooperation between the Slovak Republic and Germany in the field of development of diagnostic methods to improve the safety and availability of WWER-type reactors are presented. Signals of the standard diagnostic instrumentation of the WWER-type reactors of units 1,2 and 4 at the nuclear power plant Dukovany (EDU) in Czech Republic were analyzed. Mechanical vibrations like pendular and vertical movements of the reactor pressure vessel and its internals as well as thermohydraulic fluctuations like fluid resonances or standing pressure waves could be identified in all the three units. Incipient changes of the mechanical and/or thermohydraulic conditions of the core can be detected by periodical analysis of the signals of the standard reactor instrumentation of WWER-types reactors. (authors)

  17. Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading.

    Science.gov (United States)

    Huisman, Elise S; Andersson, Gustav; Scott, Alexander; Reno, Carol R; Hart, David A; Thornton, Gail M

    2014-05-01

    The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon. © 2014 Anatomical Society.

  18. Epidemiology of "fragile skin": results from a survey of different skin types

    Directory of Open Access Journals (Sweden)

    Haftek M

    2013-12-01

    Full Text Available Marek Haftek,1 Christine Coutanceau,2 Charles Taïeb3 1Université Lyon 1, Laboratoire de Recherche Dermatologique, Faculté de Médecine et de Pharmacie, Lyon, 2Département Médical, Laboratoires Dermatologiques A-Derma, Lavaur, 3Public Health, Pierre Fabre SA, Paris, France Background: Epidemiologic information regarding the prevalence of "fragile skin" in different adult populations is currently limited. The objective of the current survey was to assess the occurrence of perceived "fragile skin" across different skin types in the general adult population. Methods: Individuals aged 15–65 years from five representative geographic regions (France, Spain, Sweden, Japan, and the US were interviewed and grouped into the following skin types: Caucasian North skin (n=1,218, Caucasian South skin (n=1,695, Asian skin (n=1,500, and Black skin (n=500. The main survey question was "In your opinion, do you have fragile skin?" Concepts relating to the nature and appearance of an individual's skin were also evaluated. Results: A total of 4,913 individuals were interviewed. Subjects in the Caucasian North, Caucasian South, Asian, and Black skin type groups responded positively to the question "In your opinion, do you have fragile skin?" in the following proportions: 24.44%, 29.71%, 52.67%, and 42.20%, respectively. With the exception of individuals in the Black skin group, "fragile skin" was prevalent in significantly more women than men (P<0.0001. Compared with other age categories, the prevalence of "fragile skin" was significantly higher in individuals aged 15–34 years (P<0.0001, regardless of skin type. In general, individuals reporting "fragile skin" were 2–3-fold more likely to respond positively to a series of questions relating to the nature and appearance of their skin. The prevalence of "fragile skin" was also higher in individuals who experienced dermatosis (skin lesions of any type in the previous 12 months. Conclusion: Whilst these

  19. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

    2014-03-18

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  20. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Directory of Open Access Journals (Sweden)

    Z.H. Wang

    2014-04-01

    Full Text Available SRY-related high-mobility-group box 9 (Sox9 gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs. After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  1. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    International Nuclear Information System (INIS)

    Wang, Z.H.; Li, X.L.; He, X.J.; Wu, B.J.; Xu, M.; Chang, H.M.; Zhang, X.H.; Xing, Z.; Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y.

    2014-01-01

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering

  2. Remodeling of the notochord during development of vertebral fusions in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Ytteborg, Elisabeth; Torgersen, Jacob Seilø; Pedersen, Mona E; Baeverfjord, Grete; Hannesson, Kirsten O; Takle, Harald

    2010-12-01

    Histological characterization of spinal fusions in Atlantic salmon (Salmo salar) has demonstrated shape alterations of vertebral body endplates, a reduced intervertebral space, and replacement of intervertebral cells by ectopic bone. However, the significance of the notochord during the fusion process has not been addressed. We have therefore investigated structural and cellular events in the notochord during the development of vertebral fusions. In order to induce vertebral fusions, Atlantic salmon were exposed to elevated temperatures from fertilization until they attained a size of 15g. Based on results from radiography, intermediate and terminal stages of the fusion process were investigated by immunohistochemistry and real-time quantitative polymerase chain reaction. Examination of structural extracellular matrix proteins such as Perlecan, Aggrecan, Elastin, and Laminin revealed reduced activity and reorganization at early stages in the pathology. Staining for elastic fibers visualized a thinner elastic membrane surrounding the notochord of developing fusions, and immunohistochemistry for Perlecan showed that the notochordal sheath was stretched during fusion. These findings in the outer notochord correlated with the loss of Aggrecan- and Substance-P-positive signals and the further loss of vacuoles from the chordocytes in the central notochord. At more progressed stages of fusion, chordocytes condensed, and the expression of Aggrecan and Substance P reappeared. The hyperdense regions seem to be of importance for the formation of notochordal tissue into bone. Thus, the remodeling of notochord integrity by reduced elasticity, structural alterations, and cellular changes is probably involved in the development of vertebral fusions.

  3. First results with the yin-yang type electron cyclotron resonance ion source

    International Nuclear Information System (INIS)

    Suominen, P.; Ropponen, T.; Koivisto, H.

    2007-01-01

    Highly charged heavy-ion beams are often produced with Electron Cyclotron Resonance Ion Sources (ECRIS). The so-called conventional minimum-B ECRIS design includes two solenoid magnets and a multipole magnet (usually a hexapole). A minimum-B configuration can also be formed with 'yin-yang' ('baseball') type coils. Such a magnetic field configuration has been extensively tested in magnetic fusion experiments but not for the production of highly charged heavy ions. The application of the afore-mentioned coil structure to the production of multiply charged ion beams was studied. In this paper we present a design of a yin-yang type ion source known as the ARC-ECRIS and some preliminary experimental results. As a result of this work it was found that the ARC-ECRIS plasma is stable and capable of producing multiply charged ions. Many compromises were made in order to keep the costs of the prototype low. As a consequence, significant improvement can be expected in performance if the plasma size is increased and magnetic confinement is improved. At the end of this article an evolution model of the ARC-ECRIS and some future prospects are presented

  4. Biophysical Stimuli: A Review of Electrical and Mechanical Stimulation in Hyaline Cartilage.

    Science.gov (United States)

    Vaca-González, Juan J; Guevara, Johana M; Moncayo, Miguel A; Castro-Abril, Hector; Hata, Yoshie; Garzón-Alvarado, Diego A

    2017-09-01

    Objective Hyaline cartilage degenerative pathologies induce morphologic and biomechanical changes resulting in cartilage tissue damage. In pursuit of therapeutic options, electrical and mechanical stimulation have been proposed for improving tissue engineering approaches for cartilage repair. The purpose of this review was to highlight the effect of electrical stimulation and mechanical stimuli in chondrocyte behavior. Design Different information sources and the MEDLINE database were systematically revised to summarize the different contributions for the past 40 years. Results It has been shown that electric stimulation may increase cell proliferation and stimulate the synthesis of molecules associated with the extracellular matrix of the articular cartilage, such as collagen type II, aggrecan and glycosaminoglycans, while mechanical loads trigger anabolic and catabolic responses in chondrocytes. Conclusion The biophysical stimuli can increase cell proliferation and stimulate molecules associated with hyaline cartilage extracellular matrix maintenance.

  5. GLOBULAR CLUSTER POPULATIONS: FIRST RESULTS FROM S{sup 4}G EARLY-TYPE GALAXIES

    Energy Technology Data Exchange (ETDEWEB)

    Zaritsky, Dennis [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Aravena, Manuel [Núcleo de Astronomía, Facultad de Ingeniería, Universidad Diego Portales, Avenida Ejército 441, Santiago (Chile); Athanassoula, E.; Bosma, Albert [Aix Marseille Université, CNRS, LAM (Laboratoire d' Astrophysique de Marseille) UMR 7326, F-13388 Marseille (France); Comerón, Sébastien; Laine, Jarkko; Laurikainen, Eija; Salo, Heikki [Astronomy Division, Department of Physics, P.O. Box 3000, FI-90014 University of Oulu (Finland); Elmegreen, Bruce G. [IBM T. J. Watson Research Center, 1101 Kitchawan Road, Yorktown Heights, NY 10598 (United States); Erroz-Ferrer, Santiago; Knapen, Johan H. [Instituto de Astrofísica de Canarias, Vía Lácteas, E-38205 La Laguna (Spain); Gadotti, Dimitri A.; Muñoz-Mateos, Juan Carlos [European Southern Observatory, Casilla 19001, Santiago 19 (Chile); Hinz, Joannah L. [MMT Observatory, P.O. Box 210065, Tucson, AZ 85721 (United States); Ho, Luis C. [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China); Holwerda, Benne [Leiden Observatory, University of Leiden, Niels Bohrweg 4, NL-2333 Leiden (Netherlands); Sheth, Kartik, E-mail: dennis.zaritsky@gmail.com [National Radio Astronomy Observatory/NAASC, 520 Edgemont Road, Charlottesville, VA 22903 (United States)

    2015-02-01

    Using 3.6 μm images of 97 early-type galaxies, we develop and verify methodology to measure globular cluster populations from the S{sup 4}G survey images. We find that (1) the ratio, T {sub N}, of the number of clusters, N {sub CL}, to parent galaxy stellar mass, M {sub *}, rises weakly with M {sub *} for early-type galaxies with M {sub *} > 10{sup 10} M {sub ☉} when we calculate galaxy masses using a universal stellar initial mass function (IMF) but that the dependence of T {sub N} on M {sub *} is removed entirely once we correct for the recently uncovered systematic variation of IMF with M {sub *}; and (2) for M {sub *} < 10{sup 10} M {sub ☉}, there is no trend between N {sub CL} and M {sub *}, the scatter in T {sub N} is significantly larger (approaching two orders of magnitude), and there is evidence to support a previous, independent suggestion of two families of galaxies. The behavior of N {sub CL} in the lower-mass systems is more difficult to measure because these systems are inherently cluster-poor, but our results may add to previous evidence that large variations in cluster formation and destruction efficiencies are to be found among low-mass galaxies. The average fraction of stellar mass in clusters is ∼0.0014 for M {sub *} > 10{sup 10} M {sub ☉} and can be as large as ∼0.02 for less massive galaxies. These are the first results from the S{sup 4}G sample of galaxies and will be enhanced by the sample of early-type galaxies now being added to S{sup 4}G and complemented by the study of later-type galaxies within S{sup 4}G.

  6. Uncertainty analysis for results of thermal hydraulic codes of best-estimate-type

    International Nuclear Information System (INIS)

    Alva N, J.

    2010-01-01

    In this thesis, some fundamental knowledge is presented about uncertainty analysis and about diverse methodologies applied in the study of nuclear power plant transient event analysis, particularly related to thermal hydraulics phenomena. These concepts and methodologies mentioned in this work come from a wide bibliographical research in the nuclear power subject. Methodologies for uncertainty analysis have been developed by quite diverse institutions, and they have been widely used worldwide for application to results from best-estimate-type computer codes in nuclear reactor thermal hydraulics and safety analysis. Also, the main uncertainty sources, types of uncertainties, and aspects related to best estimate modeling and methods are introduced. Once the main bases of uncertainty analysis have been set, and some of the known methodologies have been introduced, it is presented in detail the CSAU methodology, which will be applied in the analyses. The main objective of this thesis is to compare the results of an uncertainty and sensibility analysis by using the Response Surface Technique to the application of W ilks formula, apply through a loss coolant experiment and an event of rise in a BWR. Both techniques are options in the part of uncertainty and sensibility analysis of the CSAU methodology, which was developed for the analysis of transients and accidents at nuclear power plants, and it is the base of most of the methodologies used in licensing of nuclear power plants practically everywhere. Finally, the results of applying both techniques are compared and discussed. (Author)

  7. Carnosol Inhibits Pro-Inflammatory and Catabolic Mediators of Cartilage Breakdown in Human Osteoarthritic Chondrocytes and Mediates Cross-Talk between Subchondral Bone Osteoblasts and Chondrocytes.

    Directory of Open Access Journals (Sweden)

    Christelle Sanchez

    Full Text Available The aim of this work was to evaluate the effects of carnosol, a rosemary polyphenol, on pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes and via bone-cartilage crosstalk.Osteoarthritic (OA human chondrocytes were cultured in alginate beads for 4 days in presence or absence of carnosol (6 nM to 9 μM. The production of aggrecan, matrix metalloproteinase (MMP-3, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-6 and nitric oxide (NO and the expression of type II collagen and ADAMTS-4 and -5 were analyzed. Human osteoblasts from sclerotic (SC or non-sclerotic (NSC subchondral bone were cultured for 3 days in presence or absence of carnosol before co-culture with chondrocytes. Chondrocyte gene expression was analyzed after 4 days of co-culture.In chondrocytes, type II collagen expression was significantly enhanced in the presence of 3 μM carnosol (p = 0.008. MMP-3, IL-6, NO production and ADAMTS-4 expression were down-regulated in a concentration-dependent manner by carnosol (p<0.01. TIMP-1 production was slightly increased at 3 μM (p = 0.02 and ADAMTS-5 expression was decreased from 0.2 to 9 μM carnosol (p<0.05. IL-6 and PGE2 production was reduced in the presence of carnosol in both SC and NSC osteoblasts while alkaline phosphatase activity was not changed. In co-culture experiments preincubation of NSC and SC osteoblasts wih carnosol resulted in similar effects to incubation with anti-IL-6 antibody, namely a significant increase in aggrecan and decrease in MMP-3, ADAMTS-4 and -5 gene expression by chondrocytes.Carnosol showed potent inhibition of pro-inflammatory and catabolic mediators of cartilage breakdown in chondrocytes. Inhibition of matrix degradation and enhancement of formation was observed in chondrocytes cocultured with subchondral osteoblasts preincubated with carnosol indicating a cross-talk between these two cellular compartments, potentially mediated via inhibition of IL-6 in

  8. Mechanical response of biopolymer double networks

    Science.gov (United States)

    Carroll, Joshua; Das, Moumita

    We investigate a double network model of articular cartilage (AC) and characterize its equilibrium mechanical response. AC has very few cells and the extracellular matrix mainly determines its mechanical response. This matrix can be thought of as a double polymer network made of collagen and aggrecan. The collagen fibers are stiff and resist tension and compression forces, while aggrecans are flexible and control swelling and hydration. We construct a microscopic model made of two interconnected disordered polymer networks, with fiber elasticity chosen to qualitatively mimic the experimental system. We study the collective mechanical response of this double network as a function of the concentration and stiffness of the individual components as well as the strength of the connection between them using rigidity percolation theory. Our results may provide a better understanding of mechanisms underlying the mechanical resilience of AC, and more broadly may also lead to new perspectives on the mechanical response of multicomponent soft materials. This work was partially supported by a Cottrell College Science Award.

  9. Automatically explaining machine learning prediction results: a demonstration on type 2 diabetes risk prediction.

    Science.gov (United States)

    Luo, Gang

    2016-01-01

    Predictive modeling is a key component of solutions to many healthcare problems. Among all predictive modeling approaches, machine learning methods often achieve the highest prediction accuracy, but suffer from a long-standing open problem precluding their widespread use in healthcare. Most machine learning models give no explanation for their prediction results, whereas interpretability is essential for a predictive model to be adopted in typical healthcare settings. This paper presents the first complete method for automatically explaining results for any machine learning predictive model without degrading accuracy. We did a computer coding implementation of the method. Using the electronic medical record data set from the Practice Fusion diabetes classification competition containing patient records from all 50 states in the United States, we demonstrated the method on predicting type 2 diabetes diagnosis within the next year. For the champion machine learning model of the competition, our method explained prediction results for 87.4 % of patients who were correctly predicted by the model to have type 2 diabetes diagnosis within the next year. Our demonstration showed the feasibility of automatically explaining results for any machine learning predictive model without degrading accuracy.

  10. [Molecular pathogenesis of Waardenburg syndrome type II resulting from SOX10 gene mutation].

    Science.gov (United States)

    Zhang, Hua; Chen, Hongsheng; Feng, Yong; Qian, Minfei; Li, Jiping; Liu, Jun; Zhang, Chun

    2016-08-01

    To explore the molecular mechanism of Waardenburg syndrome type II (WS2) resulting from SOX10 gene mutation E248fs through in vitro experiment. 293T cells were transiently transfected with wild type (WT) SOX10 and mutant type (MT) E248fs plasmids. The regulatory effect of WT/MT SOX10 on the transcriptional activity of MITF gene and influence of E248fs on WT SOX10 function were determined with a luciferase activity assay. The DNA binding capacity of the WT/MT SOX10 with the promoter of the MITF gene was determined with a biotinylated double-stranded oligonucleotide probe containing the SOX10 binding sequence cattgtc to precipitate MITF and E248fs, respectively. The stability of SOX10 and E248fs were also analyzed. As a loss-of-function mutation, the E248fs mutant failed to transactivate the MITF promoter as compared with the WT SOX10 (P<0.01), which also showed a dominant-negative effect on WT SOX10. The WT SOX10 and E248fs mutant were also able to bind specifically to the cattgtc motif in the MITF promoter, whereas E248fs had degraded faster than WT SOX10. Despite the fact that the E248fs has a dominant-negative effect on SOX10, its reduced stability may down-regulate the transcription of MITF and decrease the synthesis of melanin, which may result in haploinsufficiency of SOX10 protein and cause the milder WS2 phenotype.

  11. An evaluation of chondrocyte morphology and gene expression on superhydrophilic vertically-aligned multi-walled carbon nanotube films

    International Nuclear Information System (INIS)

    Antonioli, Eliane; Lobo, Anderson O.; Ferretti, Mario; Cohen, Moisés; Marciano, Fernanda R.; Corat, Evaldo J.; Trava-Airoldi, Vladimir J.

    2013-01-01

    Cartilage serves as a low-friction and wear-resistant articulating surface in diarthrodial joints and is also important during early stages of bone remodeling. Recently, regenerative cartilage research has focused on combinations of cells paired with scaffolds. Superhydrophilic vertically aligned carbon nanotubes (VACNTs) are of particular interest in regenerative medicine. The aim of this study is to evaluate cell expansion of human articular chondrocytes on superhydrophilic VACNTs, as well as their morphology and gene expression. VACNT films were produced using a microwave plasma chamber on Ti substrates and submitted to an O 2 plasma treatment to make them superhydrophilic. Human chondrocytes were cultivated on superhydrophilic VACNTs up to five days. Quantitative RT-PCR was performed to measure type I and type II Collagen, Sox9, and Aggrecan mRNA expression levels. The morphology was analyzed by scanning electron microscopy (SEM) and confocal microscopy. SEM images demonstrated that superhydrophilic VACNTs permit cell growth and adhesion of human chondrocytes. The chondrocytes had an elongated morphology with some prolongations. Chondrocytes cultivated on superhydrophilic VACNTs maintain the level expression of Aggrecan, Sox9, and Collagen II determined by qPCR. This study was the first to indicate that superhydrophilic VACNTs may be used as an efficient scaffold for cartilage or bone repair. Highlights: ► Chondrocytes were cultivated on Superhydrophilic Vertically Aligned Multiwall Carbon Nanotubes (VACNT). ► We have shown a correlation between gene expression and thermodynamics aspects. ► Superhydrhophilic VACNT will be an excellent substrate for cartilage and bone tissue regeneration.

  12. An evaluation of chondrocyte morphology and gene expression on superhydrophilic vertically-aligned multi-walled carbon nanotube films

    Energy Technology Data Exchange (ETDEWEB)

    Antonioli, Eliane, E-mail: eliane.antonioli@einstein.br [Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Lobo, Anderson O., E-mail: aolobo@univap.br [Laboratory of Biomedical Nanotechnology, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Ferretti, Mario, E-mail: ferretti@einstein.br [Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Ortophedic Division, Federal University of Sao Paulo, SP (Brazil); Cohen, Moises, E-mail: m.cohen@uol.com.br [Research and Education Institute, Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil); Ortophedic Division, Federal University of Sao Paulo, SP (Brazil); Marciano, Fernanda R., E-mail: femarciano@uol.com.br [Laboratory of Biomedical Nanotechnology, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Corat, Evaldo J., E-mail: corat@las.inpe.br [Laboratorio Associado de Sensores e Materiais, Instituto Nacional de Pesquisas Espaciais, Sao Jose dos Campos, Sao Paulo (Brazil); Trava-Airoldi, Vladimir J., E-mail: vladimir@las.inpe.br [Laboratorio Associado de Sensores e Materiais, Instituto Nacional de Pesquisas Espaciais, Sao Jose dos Campos, Sao Paulo (Brazil)

    2013-03-01

    Cartilage serves as a low-friction and wear-resistant articulating surface in diarthrodial joints and is also important during early stages of bone remodeling. Recently, regenerative cartilage research has focused on combinations of cells paired with scaffolds. Superhydrophilic vertically aligned carbon nanotubes (VACNTs) are of particular interest in regenerative medicine. The aim of this study is to evaluate cell expansion of human articular chondrocytes on superhydrophilic VACNTs, as well as their morphology and gene expression. VACNT films were produced using a microwave plasma chamber on Ti substrates and submitted to an O{sub 2} plasma treatment to make them superhydrophilic. Human chondrocytes were cultivated on superhydrophilic VACNTs up to five days. Quantitative RT-PCR was performed to measure type I and type II Collagen, Sox9, and Aggrecan mRNA expression levels. The morphology was analyzed by scanning electron microscopy (SEM) and confocal microscopy. SEM images demonstrated that superhydrophilic VACNTs permit cell growth and adhesion of human chondrocytes. The chondrocytes had an elongated morphology with some prolongations. Chondrocytes cultivated on superhydrophilic VACNTs maintain the level expression of Aggrecan, Sox9, and Collagen II determined by qPCR. This study was the first to indicate that superhydrophilic VACNTs may be used as an efficient scaffold for cartilage or bone repair. Highlights: Black-Right-Pointing-Pointer Chondrocytes were cultivated on Superhydrophilic Vertically Aligned Multiwall Carbon Nanotubes (VACNT). Black-Right-Pointing-Pointer We have shown a correlation between gene expression and thermodynamics aspects. Black-Right-Pointing-Pointer Superhydrhophilic VACNT will be an excellent substrate for cartilage and bone tissue regeneration.

  13. Results of Operative and Nonoperative Treatment of Rockwood Types III and V Acromioclavicular Joint Dislocation

    Science.gov (United States)

    Joukainen, Antti; Kröger, Heikki; Niemitukia, Lea; Mäkelä, E. Antero; Väätäinen, Urho

    2014-01-01

    Background: The optimal treatment of acute, complete dislocation of the acromioclavicular joint (ACJ) is still unresolved. Purpose: To determine the difference between operative and nonoperative treatment in acute Rockwood types III and V ACJ dislocation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: In the operative treatment group, the ACJ was reduced and fixed with 2 transarticular Kirschner wires and ACJ ligament suturing. The Kirschner wires were extracted after 6 weeks. Nonoperatively treated patients received a reduction splint for 4 weeks. At the 18- to 20-year follow-up, the Constant, University of California at Los Angeles Shoulder Rating Scale (UCLA), Larsen, and Simple Shoulder Test (SST) scores were obtained, and clinical and radiographic examinations of both shoulders were performed. Results: Twenty-five of 35 potential patients were examined at the 18- to 20-year follow-up. There were 11 patients with Rockwood type III and 14 with type V dislocations. Delayed surgical treatment for ACJ was used in 2 patients during follow-up: 1 in the operatively treated group and 1 in the nonoperatively treated group. Clinically, ACJs were statistically significantly less prominent or unstable in the operative group than in the nonoperative group (normal/prominent/unstable: 9/4/3 and 0/6/3, respectively; P = .02) and in the operative type III (P = .03) but not type V dislocation groups. In operatively and nonoperatively treated patients, the mean Constant scores were 83 and 85, UCLA scores 25 and 27, Larsen scores 11 and 11, and SST scores 11 and 12 at follow-up, respectively. There were no statistically significant differences in type III and type V dislocations. In the radiographic analysis, the ACJ was wider in the nonoperative than the operative group (8.3 vs 3.4 mm; P = .004), and in the type V dislocations (nonoperative vs operative: 8.5 vs 2.4 mm; P = .007). There was no statistically significant difference between study groups in

  14. Chondrogenic differentiation of human mesenchymal stem cells cultured in a cobweb-like biodegradable scaffold

    International Nuclear Information System (INIS)

    Chen Guoping; Liu Dechang; Tadokoro, Mika; Hirochika, Rei; Ohgushi, Hajime; Tanaka, Junzo; Tateishi, Tetsuya

    2004-01-01

    Human mesenchymal stem cells (MSCs) were cultured in vitro in a cobweb-like biodegradable polymer scaffold: a poly(DL-lactic-co-glycolic acid)-collagen hybrid mesh in serum-free DMEM containing TGF-β3 for 1-10 weeks. The cells adhered to the hybrid mesh, distributed evenly, and proliferated to fill the spaces in the scaffold. The ability of the cells to express gene encoding type I collagen decreased, whereas its ability to express type II collagen and aggrecan increased. Histological examination by HE staining indicated that the cells showed fibroblast morphology at the early stage and became round after culture for 4 weeks. The cartilaginous matrices were positively stained by safranin O and toluidine blue. Immunostaining with anti-type II collagen and anti-cartilage proteoglycan showed that type II collagen and cartilage proteoglycan were detected around the cells. In addition, a homogeneous distribution of cartilaginous extracellular matrices was detected around the cells. These results suggest the chondrogenic differentiation of the mesenchymal stem cells in the hybrid mesh. The PLGA-collagen hybrid mesh enabled the aggregation of mesenchymal stem cells and provided a promotive microenvironment for the chondrogenic differentiation of the MSCs

  15. Three-Dimensional Coculture of Meniscal Cells and Mesenchymal Stem Cells in Collagen Type I Hydrogel on a Small Intestinal Matrix-A Pilot Study Toward Equine Meniscus Tissue Engineering.

    Science.gov (United States)

    Kremer, Antje; Ribitsch, Iris; Reboredo, Jenny; Dürr, Julia; Egerbacher, Monika; Jenner, Florien; Walles, Heike

    2017-05-01

    Meniscal injuries are the most frequently encountered soft tissue injuries in the equine stifle joint. Due to the inherent limited repair potential of meniscal tissue, meniscal injuries do not only affect the meniscus itself but also lead to impaired joint homeostasis and secondary osteoarthritis. The presented study compares 3D coculture constructs of primary equine mesenchymal stem cells (MSC) and meniscus cells (MC) seeded on three different scaffolds-a cell-laden collagen type I hydrogel (Col I gel), a tissue-derived small intestinal matrix scaffold (SIS-muc) and a combination thereof-for their qualification to be applied for meniscus tissue engineering. To investigate cell attachment of primary MC and MSC on SIS-muc matrix SEM pictures were performed. For molecular analysis, lyophilized samples of coculture constructs with different cell ratios (100% MC, 100% MSC, and 50% MC and 50% MSC, 20% MC, and 80% MSC) were digested and analyzed for DNA and GAG content. Active matrix remodeling of 3D coculture models was indicated by matrix metalloproteinases detection. For comparison of tissue-engineered constructs with the histologic architecture of natural equine menisci, paired lateral and medial menisci of 15 horses representing different age groups were examined. A meniscus phenotype with promising similarity to native meniscus tissue in its GAG/DNA expression in addition to Col I, Col II, and Aggrecan production was achieved using a scaffold composed of Col I gel on SIS-muc combined with a coculture of MC and MSC. The results encourage further development of this scaffold-cell combination for meniscus tissue engineering.

  16. First results on the charge collection properties of segmented detectors made with p-type bulk silicon

    International Nuclear Information System (INIS)

    Casse, G.; Allport, P.P.; Bowcock, T.J.V.; Greenall, A.; Hanlon, M.; Jackson, J.N.

    2002-01-01

    Radiation damage of n-type bulk detectors introduces stable defects acting as effective p-type doping and leads to the change of the conductivity type of the silicon substrate (type inversion) after a fluence of a few times 10 13 protons cm -2 . The diode junction after inversion migrates from the original side to the back plane of the detector. The migration of the junction can be prevented using silicon detectors with p-type substrates. Furthermore, the use of n-side readout gives higher charge collection efficiency for segmented devices operated below the full depletion voltage. Large area (∼6.4x6.4 cm 2 ) capacitively coupled 80 μm pitch detectors using polysilicon bias resistors have been fabricated on p-type substrates (n-in-p diode structure). These detectors have been irradiated with 24 GeV/c protons to an integrated fluence of 3x10 14 cm -2 and kept for 7 days at 25 deg. C to reach the broad minimum of the annealing curve. Results are presented on the comparison of their charge collection properties with detectors using p-strip read-out after corresponding dose and annealing

  17. Guideline treatment results in regression of atherosclerosis in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Strang, Aart C.; van Wijk, Diederik F.; Mutsaerts, Henri J. M. M.; Stroes, Erik S. G.; Nederveen, Aart J.; Rotmans, Joris I.; Rabelink, Ton J.; Box, Frieke M. A.

    2015-01-01

    Efficacy of guideline cardiovascular disease prevention regimens may differ between patients with or without type II diabetes mellitus. We therefore compared change in carotid artery wall dimensions in type II diabetes mellitus and non-type II diabetes mellitus patients with a history of a major

  18. results on an integral inequality of the opial- type

    African Journals Online (AJOL)

    We obtain integral inequalities which are Opial-type inequalities, mainly by using Jensen's inequality for the case of convex function. KEYWORDS: Integral inequalities, Opial's inequality, Jensen's inequality and convex functions. 2010 Subject Classification: 15A31. INTRODUCTION. Opial ([8])established the following ...

  19. Tumor type resulting in upgrade: An analysis based on 333 low grade soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Langer, Stefan

    2014-11-01

    Full Text Available [english] Introduction: Soft tissue sarcomas (STS are rare tumors. Based on histopathological criteria, three grades are distinguished from low (G1 to intermediate (G2 and high grade (G3. After complete initial surgical resection, some G1 STS recur as lesions with an upgrade of a previous G1 STS to a recurrent G2 STS. This upgrade indicates higher malignancy of the STS. Our aim was to find possible risk factors for these upgrades including age, localization of tumor and tumor type. Methods: This retrospective case-control study evaluated 333 patients. Of these 333, 54.7% were male and 45.3% female. All patients underwent R0 resections and among these, 10% subsequently upgraded. The processed data include age, gender, tumor type, tumor localization, local recurrence and upgrade. Results: Patients with upgrades have a higher mean age of 5.5 years than our reference collective. The tumor type has a significant effect on upgrades. Patients with fibrosarcomas are at a threefold risk of an upgrade compared to patients with other G1 STS.Conclusion: Our results indicate that age and tumor type play a key role in upgrades in G1 STS. Patients, age 60 and above and diagnosed with G1 fibrosarcomas, are three times as likely to upgrade compared to patients younger than 60 with other G1 STS. We discuss the significance of these risk factors and whether aside from complete tumor resection, additional therapies (e.g. irradiation may be applied to improve therapeutic outcome.

  20. Some results on rotating fluid balls of Petrov type D

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, M [Department of Physics, Umeaa University, SE-901 87 Umeaa (Sweden); Eriksson, D [Department of Physics, Umeaa University, SE-901 87 Umeaa (Sweden); Fodor, G [KFKI Research Institute for Particle and Nuclear Physics, H-1525, Budapest 114, P.O.B. 49 (Hungary); Racz, I [KFKI Research Institute for Particle and Nuclear Physics, H-1525, Budapest 114, P.O.B. 49 (Hungary)

    2007-05-15

    The second order perturbative field equations for slowly and rigidly rotating perfect fluid balls of Petrov type D are solved numerically. It is found that all the slowly and rigidly rotating perfect fluid balls up to second order, irrespective of Petrov type, may be matched to a possibly non-asymptotically flat stationary axisymmetric vacuum exterior. A subspace of the parameter space is identified for which the solutions can be matched to an asymptotically flat exterior vacuum region. The physical properties like equations of state, shapes and speeds of sound are determined for a number of solutions.

  1. Antioxidant effects of betulin on porcine chondrocyte behavior in gelatin/C6S/C4S/HA modified tricopolymer scaffold

    International Nuclear Information System (INIS)

    Lin, Wen-Yang; Lin, Feng-Huei; Sadhasivam, S.; Savitha, S.

    2010-01-01

    The antioxidant effects of betulin on porcine chondrocytes cultured in gelatin/C6S/C4S/HA modified tricopolymer scaffold for a period of 4 weeks was investigated. The porous structure of the scaffold and cell attachment was observed by scanning electron microscopy (SEM). Biochemical measures of necrosis, cell proliferation, sulfated glycosaminoglycans (sGAG) content and extracellular matrix related gene expressions were quantitatively evaluated. The cell proliferation data showed good cellular viability in tricopolymer scaffold and increased optical density for total DNA demonstrated that the cells continued to proliferate inside the scaffold. The sGAG production indicated chondrogenic differentiation. Chondrocytes treated with betulin expressed transcripts encoding type II collagen, aggrecan, and decorin. To conclude, the substantiated results supported cell proliferation, production of extracellular matrix proteins and down-regulation of matrix metalloproteases and cytokine, in betulin treated scaffolds.

  2. Antioxidant effects of betulin on porcine chondrocyte behavior in gelatin/C6S/C4S/HA modified tricopolymer scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Wen-Yang; Lin, Feng-Huei [Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan (China); Sadhasivam, S., E-mail: rahulsbio@yahoo.co.in [Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan (China); Savitha, S. [Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan (China)

    2010-05-10

    The antioxidant effects of betulin on porcine chondrocytes cultured in gelatin/C6S/C4S/HA modified tricopolymer scaffold for a period of 4 weeks was investigated. The porous structure of the scaffold and cell attachment was observed by scanning electron microscopy (SEM). Biochemical measures of necrosis, cell proliferation, sulfated glycosaminoglycans (sGAG) content and extracellular matrix related gene expressions were quantitatively evaluated. The cell proliferation data showed good cellular viability in tricopolymer scaffold and increased optical density for total DNA demonstrated that the cells continued to proliferate inside the scaffold. The sGAG production indicated chondrogenic differentiation. Chondrocytes treated with betulin expressed transcripts encoding type II collagen, aggrecan, and decorin. To conclude, the substantiated results supported cell proliferation, production of extracellular matrix proteins and down-regulation of matrix metalloproteases and cytokine, in betulin treated scaffolds.

  3. Expression of collagen type I and II, aggrecan and SOX9 genes in mesenchymal stem cells on different bioscaffolds

    Directory of Open Access Journals (Sweden)

    Mahdieh Ghiasi

    2015-06-01

    Conclusion: The use of natural fibrin glue scaffold can be considered as a suitable environment for proliferation and differentiation of adipose-derived mesenchymal stem cells in cartilage tissue engineering.

  4. Evaluation of ANSYS time history analysis results according to the input type

    International Nuclear Information System (INIS)

    Kim, In Yong; Kim, Tae Wan; Nam, Kung In; Park, Keun Bae

    1996-04-01

    This report discusses and analyzes the analysis reliability of dynamic analysis according to the type of input time history when using commercial FEM analysis code ANSYS. The dynamic analysis using ANSYS with displacement time history, and GT/STRUDL with displacement time history for the same model were carried out and compared. The ANSYS results with displacement time history were more conservative than that with acceleration time history, and showed an unstable characteristic depending on the input directions. The results of analysis using ANSYS with acceleration time history. To review the effect on the analysis for the NSSS structures, CEDM seismic analysis using ANSYS was done. The input time history is comprised of SSE, OBE, and BLPB cases. The comparisons are made by the acceleration floor response spectra of each case obtained after postprocessing of analysis results. The seismic analysis with displacement time history exhibited more conservative results than those with acceleration time history. In conclusion, a time history analysis using ANSYS with displacement time history may give overly conservative results. Hence displacement time history option in ANSYS requires a careful consideration, and it is recommended to use the acceleration time history option if possible. 6 tabs., 22 figs., 7 refs. (Author) .new

  5. Glomerular Podocytes Express Type 1 Adenylate Cyclase: Inactivation Results in Susceptibility to Proteinuria

    Science.gov (United States)

    Xiao, Zhijie; He, Liqun; Takemoto, Minoru; Jalanko, Hannu; Chan, Guy C.; Storm, Daniel R.; Betsholtz, Christer; Tryggvason, Karl; Patrakka, Jaakko

    2011-01-01

    Background/Aims The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1–/–). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1–/– mice. However, albumin overload resulted in severe albuminuria in Adcy1–/– mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. PMID:21196775

  6. Differential population synthesis of early-type galaxies. III. Synthesis results

    International Nuclear Information System (INIS)

    Pickles, A.J.

    1985-01-01

    Synthesis results are presented for 12 elliptical and five lenticular galaxies which cover nearly a 6 mag range of absolute magnitude in the Fornax cluster (V = 1430 km s -1 ). The results of age, metallicity, and mass-to-light ratio (M/L) determinations are presented differentially as functions of galactic luminosity and morphology. Bright elliptical galaxies are well represented by main-sequence turnoff colors of (V-R)/sub c/roughly-equal0.37 and B-Vroughly-equal0.70, in good agreement with O'Connell's results for bright Virgo ellipticals. The relatively young main-sequence turnoff ages, of 6-10 Gyr for ellipticals of all luminosities, indicate that substantial star formation activity occurred in these galaxies for a period of 6dagger10 Gyr after the epoch of globular cluster formation. There is strong evidence for small amounts of current star formation in at least the brightest ellipticals of all luminosities, indicate that substantial star formation in at least the brightest ellipticals, variation in the amount of which may account for significant dispersion in the cluster U-V versus V color-magnitude relation. A metallicity gradient in [Fe/H] of at least 0.16 dex per absolute magnitude is derived, with the brightest ellipticals being 2 to 3 times more metal-rich than solar. The mean metallicities and turnoff ages of the faintest ellipticals are probably dependent on environment. Distance-independent upper limits to galaxy M/L ratios derived from the syntheses conform well with M/L ratios derived from velocity dispersion measurements and give no evidence for unseen mass in the nuclei of early type galaxies of any luminosity

  7. Test results of Salmonella typing by the NRLs-Salmonella in the Member States of the EU and the EnterNet Laboratories - Collaborative study VI on typing of Salmonella

    NARCIS (Netherlands)

    Korver H; Raes M; Maas HME; Ward LR; Wannet WJB; Henken AM; PHLS-Colindale/London; MGB; LIS

    2002-01-01

    Test results of Salmonella sero- and phage typing and antimicrobial susceptibility testing by the National Reference Laboratories for Salmonella in the Member States of the European Union and the EnterNet Laboratories: Collaborative study VI (2001) for Salmonella. The sixth collaborative typing

  8. Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines

    International Nuclear Information System (INIS)

    Thirunavukkarasu, Kannan; Pei, Yong; Moore, Terry L.; Wang, He; Yu, Xiao-peng; Geiser, Andrew G.; Chandrasekhar, Srinivasan

    2006-01-01

    ADAMTS-4 (aggrecanase-1) is a metalloprotease that plays a role in aggrecan degradation in the cartilage extracellular matrix. In order to understand the regulation of ADAMTS-4 gene expression we have cloned and characterized a functional 4.5 kb human ADAMTS-4 promoter. Sequence analysis of the promoter revealed the presence of putative binding sites for nuclear factor of activated T cells (NFAT) and Runx family of transcription factors that are known to regulate chondrocyte maturation and differentiation. Using promoter-reporter assays and mRNA analysis we have analyzed the role of chondrocyte-expressed transcription factors NFATp and Runx2 and have shown that ADAMTS-4 is a potential downstream target of these two factors. Our results suggest that inhibition of the expression/function of NFATp and/or Runx2 may enable us to modulate aggrecan degradation in normal physiology and/or in degenerative joint diseases. The ADAMTS-4 promoter would serve as a valuable mechanistic tool to better understand the regulation of ADAMTS-4 expression by signaling pathways that modulate cartilage matrix breakdown

  9. Training in virtual reality: qualitative results from a comparison of technology types

    International Nuclear Information System (INIS)

    Sebok, Angelia; Nystad, Espen

    2005-08-01

    The study described in HWR-734 consisted of three experiments. The first experiment compared procedural and configuration learning using four display technology types; the second experiment compared these same four technology types in a retention and transfer of training condition, and the third experiment compared assembly learning using three types of displays. The purpose of the study was to determine if the technology types differed in their ability to support learning. Thus, several different types of learning tasks were included (i.e., procedures, configuration and assembly). For all types of learning, short term training effectiveness was evaluated: subjects were tested immediately after the training session, in the same conditions in which they had been trained. In addition, procedural learning was also evaluated in a retention and transfer of training condition, where subjects were tested 24 hours after the initial training, in a real-world talk-through condition. In the Procedural / Configuration knowledge conditions, four technology types were evaluated. These include a desktop monoscopic display (DM), a desktop stereoscopic display (DS), a large-screen stereoscopic display (LS-S), and a head-mounted display with orientation tracking. In the Assembly knowledge condition, three technology types were evaluated: a desktop monoscopic display (DM), a large-screen monoscopic display (LS-M), and a head-mounted display without orientation tracking (HMD-nt). Twenty-four employees at the Halden Boiling Water Reactor (HBWR) participated in the study. The study lasted for one week, so all subjects attended for multiple days. Prior to starting the experiment, subjects attended a briefing where they were given instructions on how to use the equipment. They were allowed 10 minutes practice to get familiar with each technology type before each experimental session. During and after the experimental sessions, data were collected. These included objective data, such as

  10. Experimental results of current distribution in Rutherford-type LHC cables

    CERN Document Server

    Verweij, A P

    2000-01-01

    Current distribution among the wires of multi-strand superconducting cables is an important item for accelerator magnets. A non-uniform distribution could cause additional field distortions in the magnet bore and can as well be one of the reasons of premature quenching. Since two years electrical measurements on superconducting Rutherford-type cables are performed at CERN as part of the reception tests for the Large Hadron Collider (LHC). Cable samples of 2.4 m length are tested at currents up to 32 kA, temperatures around 1.9 and 4.3 K, and fields up to 10 T, applied perpendicularly as well as parallel to the broad face of the cable. Last year, an array of 24 Hall probes was installed in the test set-up in order to measure the self-field of the cable samples along one cable pitch. Each of the probes measures the local field generated by the current in the strands close by, and the results of the all probes reflect therefore the distribution of the strand currents. Experiments are done varying the applied fie...

  11. Subjective sleep impairment in adults with type 1 or type 2 diabetes: Results from Diabetes MILES-The Netherlands

    NARCIS (Netherlands)

    Nefs, G.; Donga, E.; van Someren, E.J.W.; Bot, M.; Speight, J.; Pouwer, F.

    2015-01-01

    Aims: Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of

  12. Subjective sleep impairment in adults with type 1 or type 2 diabetes : Results from Diabetes MILES-The Netherlands

    NARCIS (Netherlands)

    Nefs, Giesje; Donga, Esther; van Someren, Eus; Bot, Mariska; Speight, Jane; Pouwer, François

    AIMS: Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of

  13. Omentin-1 prevents cartilage matrix destruction by regulating matrix metalloproteinases.

    Science.gov (United States)

    Li, Zhigang; Liu, Baoyi; Zhao, Dewei; Wang, BenJie; Liu, Yupeng; Zhang, Yao; Li, Borui; Tian, Fengde

    2017-08-01

    Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the extracellular matrix and pathological progression of osteoarthritis (OA). Omentin-1 is a newly identified anti-inflammatory adipokine. Little information regarding the protective effects of omentin-1 in OA has been reported before. In the current study, our results indicated that omentin-1 suppressed expression of MMP-1, MMP-3, and MMP-13 induced by the proinflammatory cytokine interleukin-1β (IL-1β) at both the mRNA and protein levels in human chondrocytes. Importantly, administration of omentin-1 abolished IL-1β-induced degradation of type II collagen (Col II) and aggrecan, the two major extracellular matrix components in articular cartilage, in a dose-dependent manner. Mechanistically, omentin-1 ameliorated the expression of interferon regulatory factor 1 (IRF-1) by blocking the JAK-2/STAT3 pathway. Our results indicate that omentin-1 may have a potential chondroprotective therapeutic capacity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Multi-virulence-locus sequence typing of Staphylococcus lugdunensis generates results consistent with a clonal population structure and is reliable for epidemiological typing.

    Science.gov (United States)

    Didi, Jennifer; Lemée, Ludovic; Gibert, Laure; Pons, Jean-Louis; Pestel-Caron, Martine

    2014-10-01

    Staphylococcus lugdunensis is an emergent virulent coagulase-negative staphylococcus responsible for severe infections similar to those caused by Staphylococcus aureus. To understand its potentially pathogenic capacity and have further detailed knowledge of the molecular traits of this organism, 93 isolates from various geographic origins were analyzed by multi-virulence-locus sequence typing (MVLST), targeting seven known or putative virulence-associated loci (atlLR2, atlLR3, hlb, isdJ, SLUG_09050, SLUG_16930, and vwbl). The polymorphisms of the putative virulence-associated loci were moderate and comparable to those of the housekeeping genes analyzed by multilocus sequence typing (MLST). However, the MVLST scheme generated 43 virulence types (VTs) compared to 20 sequence types (STs) based on MLST, indicating that MVLST was significantly more discriminating (Simpson's index [D], 0.943). No hypervirulent lineage or cluster specific to carriage strains was defined. The results of multilocus sequence analysis of known and putative virulence-associated loci are consistent with a clonal population structure for S. lugdunensis, suggesting a coevolution of these genes with housekeeping genes. Indeed, the nonsynonymous to synonymous evolutionary substitutions (dN/dS) ratio, the Tajima's D test, and Single-likelihood ancestor counting (SLAC) analysis suggest that all virulence-associated loci were under negative selection, even atlLR2 (AtlL protein) and SLUG_16930 (FbpA homologue), for which the dN/dS ratios were higher. In addition, this analysis of virulence-associated loci allowed us to propose a trilocus sequence typing scheme based on the intragenic regions of atlLR3, isdJ, and SLUG_16930, which is more discriminant than MLST for studying short-term epidemiology and further characterizing the lineages of the rare but highly pathogenic S. lugdunensis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Preferences for learning different types of genome sequencing results among young breast cancer patients: Role of psychological and clinical factors.

    Science.gov (United States)

    Kaphingst, Kimberly A; Ivanovich, Jennifer; Lyons, Sarah; Biesecker, Barbara; Dresser, Rebecca; Elrick, Ashley; Matsen, Cindy; Goodman, Melody

    2018-01-29

    The growing importance of genome sequencing means that patients will increasingly face decisions regarding what results they would like to learn. The present study examined psychological and clinical factors that might affect these preferences. 1,080 women diagnosed with breast cancer at age 40 or younger completed an online survey. We assessed their interest in learning various types of genome sequencing results: risk of preventable disease or unpreventable disease, cancer treatment response, uncertain meaning, risk to relatives' health, and ancestry/physical traits. Multivariable logistic regression was used to examine whether being "very" interested in each result type was associated with clinical factors: BRCA1/2 mutation status, prior genetic testing, family history of breast cancer, and psychological factors: cancer recurrence worry, genetic risk worry, future orientation, health information orientation, and genome sequencing knowledge. The proportion of respondents who were very interested in learning each type of result ranged from 16% to 77%. In all multivariable models, those who were very interested in learning a result type had significantly higher knowledge about sequencing benefits, greater genetic risks worry, and stronger health information orientation compared to those with less interest (p-values psychological factors. Shared decision-making approaches that increase knowledge about genome sequencing and incorporate patient preferences for health information and learning about genetic risks may help support patients' informed choices about learning different types of sequencing results. © Society of Behavioral Medicine 2018.

  16. Lack of the nucleoside transporter ENT1 results in the Augustine-null blood type and ectopic mineralization.

    Science.gov (United States)

    Daniels, Geoff; Ballif, Bryan A; Helias, Virginie; Saison, Carole; Grimsley, Shane; Mannessier, Lucienne; Hustinx, Hein; Lee, Edmond; Cartron, Jean-Pierre; Peyrard, Thierry; Arnaud, Lionel

    2015-06-04

    The Augustine-negative alias At(a-) blood type, which seems to be restricted to people of African ancestry, was identified half a century ago but remains one of the last blood types with no known genetic basis. Here we report that a nonsynonymous single nucleotide polymorphism in SLC29A1 (rs45458701) is responsible for the At(a-) blood type. The resulting p.Glu391Lys variation in the last extracellular loop of the equilibrative nucleoside transporter 1 (ENT1; also called SLC29a1) is known not to alter its ability to transport nucleosides and nucleoside analog drugs. Furthermore, we identified 3 individuals of European ancestry who are homozygous for a null mutation in SLC29A1 (c.589+1G>C) and thus have the Augustine-null blood type. These individuals lacking ENT1 exhibit periarticular and ectopic mineralization, which confirms an important role for ENT1/SLC29A1 in human bone homeostasis as recently suggested by the skeletal phenotype of aging Slc29a1(-/-) mice. Our results establish Augustine as a new blood group system and place SLC29A1 as a new candidate gene for idiopathic disorders characterized with ectopic calcification/mineralization. © 2015 by The American Society of Hematology.

  17. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    Science.gov (United States)

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  18. Laboratory results gained from cold worked type 316Ti under simulated PWR primary environment

    International Nuclear Information System (INIS)

    Devrient, B.; Kilian, R.; Koenig, G.; Widera, M.; Wermelinger, T.

    2015-01-01

    Beginning in 2005, intergranular stress corrosion cracking (IGSCC) of barrel bolts made from cold worked type 316Ti (German Material No. 1.4571 K) was observed in several S/KWU type PWRs. This mechanism was so far less understood for PWR primary conditions. Therefore an extended joint research program was launched by AREVA GmbH and VGB e.V. to clarify the specific conditions which contributed to the observed findings on barrel bolts. In the frame of this research program beneath the evaluation of the operational experience also laboratory tests on the general cracking behavior of cold worked type 316Ti material, which followed the same production line as for barrel bolt manufacturing in the eighties, with different cold work levels covering up to 30 % were performed to determine whether there is a specific susceptibility of cold worked austenitic stainless steel specimens to suffer IGSCC under simulated PWR primary conditions. All these slow strain rate tests on tapered specimens and component specimens came to the results that first, much higher cold work levels than used for the existing barrel bolts are needed for IGSCC initiation. Secondly, additional high active plastic deformation is needed to generate and propagate intergranular cracking. And thirdly, all specimens finally showed ductile fracture at the applied strain rates. (authors)

  19. The Mode of Inheritance of Scheuermann’s Disease

    Directory of Open Access Journals (Sweden)

    A. M. Zaidman

    2013-01-01

    Full Text Available The mode of Scheuermann’s disease inheritance and its phenotypic traits in probands and their relatives were studied in 90 pedigrees (90 probands and 385 relatives. The disorder was identified as a genetically related pathology inherited by autosomal dominant type, controlled by a mutant major gene, as a kyphotic deformity without signs of vertebral bodies’ anomaly and torsion. Morphological and biochemical studies showed disturbance in the structure of vertebral growth plate anterior aspects at the level of deformity, defects in proliferation and differentiation of chondrocytes, and change in proteoglycan spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes isolated from vertebral growth plates of patients with Scheuermann’s disease. The study results included disorder in the IHH gene expression and preservation of the expression of PAX1, two aggrecan isoforms, link protein, types I and II collagen, lumican, versican, growth hormone and growth factor receptor genes, and proliferation gene. Preservation of the SOX9 gene (transcription gene probably indicates posttranscriptional genetic disorders. The study is under way.

  20. Results of 15 years experiments in the PMK-2 integral-type facility for VVERs

    Energy Technology Data Exchange (ETDEWEB)

    Szabados, L.; Ezsoel, G.; Perneczky, L. [KFKI Atomic Energy Research Institute, Budapest (Hungary)

    2001-07-01

    Due to the specific features of the VVER-440/213-type reactors the transient behaviour of such a reactor system is different from the usual PWR system behaviour. To provide an experimental database for the transient behaviour of VVER systems the PMK integral-type facility, the scaled down model of the Paks NPP was designed and constructed in the early 1980's. Since the start-up of the facility 48 experiments have been performed. It was confirmed through the experiments that the facility is a suitable tool for the computer code validation experiments and to the identification of basic thermal-hydraulic phenomena occurring during plant accidents. High international interest was shown by the four Standard Problem Exercises of the IAEA and by the projects financed by the EU-PHARE. A wide range of small- and medium-size LOCA sequences have been studied to know the performance and effectiveness of ECC systems and to evaluate the thermal-hydraulic safety of the core. Extensive studies have been performed to investigate the one- and two-phase natural circulation, the effect of disturbances coming from the secondary circuit and to validate the effectiveness of accident management measures like bleed and feed. The VVER-specific case, the opening of the SG collector cover was also extensively investigated. Examples given in the report show a few results of experiments and the results of calculation analyses performed for validation purposes of codes like RELAP5, ATHLET and CATHARE. There are some other white spots in Cross Reference Matrices for VVER reactors and, therefore, further experiments are planned to perform tests primarily in further support of accident management measures at low power states of plants to facilitate the improved safety management of VVER-440-type reactors. (authors)

  1. Results of 15 years experiments in the PMK-2 integral-type facility for VVERs

    International Nuclear Information System (INIS)

    Szabados, L.; Ezsoel, G.; Perneczky, L.

    2001-01-01

    Due to the specific features of the VVER-440/213-type reactors the transient behaviour of such a reactor system is different from the usual PWR system behaviour. To provide an experimental database for the transient behaviour of VVER systems the PMK integral-type facility, the scaled down model of the Paks NPP was designed and constructed in the early 1980's. Since the start-up of the facility 48 experiments have been performed. It was confirmed through the experiments that the facility is a suitable tool for the computer code validation experiments and to the identification of basic thermal-hydraulic phenomena occurring during plant accidents. High international interest was shown by the four Standard Problem Exercises of the IAEA and by the projects financed by the EU-PHARE. A wide range of small- and medium-size LOCA sequences have been studied to know the performance and effectiveness of ECC systems and to evaluate the thermal-hydraulic safety of the core. Extensive studies have been performed to investigate the one- and two-phase natural circulation, the effect of disturbances coming from the secondary circuit and to validate the effectiveness of accident management measures like bleed and feed. The VVER-specific case, the opening of the SG collector cover was also extensively investigated. Examples given in the report show a few results of experiments and the results of calculation analyses performed for validation purposes of codes like RELAP5, ATHLET and CATHARE. There are some other white spots in Cross Reference Matrices for VVER reactors and, therefore, further experiments are planned to perform tests primarily in further support of accident management measures at low power states of plants to facilitate the improved safety management of VVER-440-type reactors. (authors)

  2. LINKING TYPE Ia SUPERNOVA PROGENITORS AND THEIR RESULTING EXPLOSIONS

    International Nuclear Information System (INIS)

    Foley, Ryan J.; Kirshner, Robert P.; Simon, Joshua D.; Burns, Christopher R.; Gal-Yam, Avishay; Hamuy, Mario; Morrell, Nidia I.; Phillips, Mark M.; Shields, Gregory A.; Sternberg, Assaf

    2012-01-01

    Comparing the ejecta velocities at maximum brightness and narrow circumstellar/interstellar Na D absorption line profiles of a sample of 23 Type Ia supernovae (SNe Ia), we determine that the properties of SN Ia progenitor systems and explosions are intimately connected. As demonstrated by Sternberg et al., half of all SNe Ia with detectable Na D absorption at the host-galaxy redshift in high-resolution spectroscopy have Na D line profiles with significant blueshifted absorption relative to the strongest absorption component, which indicates that a large fraction of SN Ia progenitor systems have strong outflows. In this study, we find that SNe Ia with blueshifted circumstellar/interstellar absorption systematically have higher ejecta velocities and redder colors at maximum brightness relative to the rest of the SN Ia population. This result is robust at a 98.9%-99.8% confidence level, providing the first link between the progenitor systems and properties of the explosion. This finding is further evidence that the outflow scenario is the correct interpretation of the blueshifted Na D absorption, adding additional confirmation that some SNe Ia are produced from a single-degenerate progenitor channel. An additional implication is that either SN Ia progenitor systems have highly asymmetric outflows that are also aligned with the SN explosion or SNe Ia come from a variety of progenitor systems where SNe Ia from systems with strong outflows tend to have more kinetic energy per unit mass than those from systems with weak or no outflows.

  3. The minor collagens in articular cartilage

    DEFF Research Database (Denmark)

    Luo, Yunyun; Sinkeviciute, Dovile; He, Yi

    2017-01-01

    Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components......, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also...... fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including...

  4. A collaborative European exercise on mRNA-based body fluid/skin typing and interpretation of DNA and RNA results

    DEFF Research Database (Denmark)

    van den Berge, M; Carracedo, A; Gomes, I

    2014-01-01

    The European Forensic Genetics Network of Excellence (EUROFORGEN-NoE) undertook a collaborative project on mRNA-based body fluid/skin typing and the interpretation of the resulting RNA and DNA data. Although both body fluids and skin are composed of a variety of cell types with different function...

  5. A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

    International Nuclear Information System (INIS)

    Purmessur, D.; Walter, B.A.; Roughley, P.J.; Laudier, D.M.; Hecht, A.C.; Iatridis, James

    2013-01-01

    Highlights: ► TNFα induced catabolic changes similar to human intervertebral disc degeneration. ► The metabolic shift induced by TNFα was sustained following removal. ► TNFα induced changes suggestive of cell senescence without affecting cell viability. ► Interventions are required to stimulate anabolism and increase cell proliferation. -- Abstract: This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in

  6. Emergent properties resulting from type-II band alignment in semiconductor nanoheterostructures.

    Science.gov (United States)

    Lo, Shun S; Mirkovic, Tihana; Chuang, Chi-Hung; Burda, Clemens; Scholes, Gregory D

    2011-01-11

    The development of elegant synthetic methodologies for the preparation of monocomponent nanocrystalline particles has opened many possibilities for the preparation of heterostructured semiconductor nanostructures. Each of the integrated nanodomains is characterized by its individual physical properties, surface chemistry, and morphology, yet, these multicomponent hybrid particles present ideal systems for the investigation of the synergetic properties that arise from the material combination in a non-additive fashion. Of particular interest are type-II heterostructures, where the relative band alignment of their constituent semiconductor materials promotes a spatial separation of the electron and hole following photoexcitation, a highly desirable property for photovoltaic applications. This article highlights recent progress in both synthetic strategies, which allow for material and architectural modulation of novel nanoheterostructures, as well as the experimental work that provides insight into the photophysical properties of type-II heterostructures. The effects of external factors, such as electric fields, temperature, and solvent are explored in conjunction with exciton and multiexciton dynamics and charge transfer processes typical for type-II semiconductor heterostructures.

  7. Chondrogenic differentiation of mesenchymal stem cells in a leakproof collagen sponge

    International Nuclear Information System (INIS)

    Chen Guoping; Akahane, Daisuke; Kawazoe, Naoki; Yamamoto, Katsuyuki; Tateishi, Tetsuya

    2008-01-01

    A three-dimensional culture of mesenchymal stem cells (MSCs) in a porous scaffold has been developed as a promising strategy for cartilage tissue engineering. The chondrogenic differentiation of MSCs derived from human bone marrow was studied by culturing the cells in a novel scaffold constructed of leakproof collagen sponge. All the surfaces of the collagen sponge except the top were wrapped with a membrane that has pores smaller than the cells to protect against cell leakage during cell seeding. The cells adhered to the collagen, distributed evenly, and proliferated to fill the spaces in the sponge. Cell seeding efficiency was greater than 95%. The MSCs cultured in the collagen sponge in the presence of TGF-β3 and BMP6 expressed a high level of genes encoding type II and type X collagen, sox9, and aggrecan. Histological examination by HE staining indicated that the differentiated cells showed a round morphology. The extracellular matrices were positively stained by safranin O and toluidine blue. Immunostaining with anti-type II collagen and anti-cartilage proteoglycan showed that type II collagen and cartilage proteoglycan were detected around the cells. These results suggest the chondrogenic differentiation of MSCs when cultured in the collagen sponge in the presence of TGF-β3 and BMP6

  8. Fibrocartilage tissue engineering: the role of the stress environment on cell morphology and matrix expression.

    Science.gov (United States)

    Thomopoulos, Stavros; Das, Rosalina; Birman, Victor; Smith, Lester; Ku, Katherine; Elson, Elliott L; Pryse, Kenneth M; Marquez, Juan Pablo; Genin, Guy M

    2011-04-01

    Although much is known about the effects of uniaxial mechanical loading on fibrocartilage development, the stress fields to which fibrocartilaginous regions are subjected to during development are mutiaxial. That fibrocartilage develops at tendon-to-bone attachments and in compressive regions of tendons is well established. However, the three-dimensional (3D) nature of the stresses needed for the development of fibrocartilage is not known. Here, we developed and applied an in vitro system to determine whether fibrocartilage can develop under a state of periodic hydrostatic tension in which only a single principal component of stress is compressive. This question is vital to efforts to mechanically guide morphogenesis and matrix expression in engineered tissue replacements. Mesenchymal stromal cells in a 3D culture were exposed to compressive and tensile stresses as a result of an external tensile hydrostatic stress field. The stress field was characterized through mechanical modeling. Tensile cyclic stresses promoted spindle-shaped cells, upregulation of scleraxis and type one collagen, and cell alignment with the direction of tension. Cells experiencing a single compressive stress component exhibited rounded cell morphology and random cell orientation. No difference in mRNA expression of the genes Sox9 and aggrecan was observed when comparing tensile and compressive regions unless the medium was supplemented with the chondrogenic factor transforming growth factor beta3. In that case, Sox9 was upregulated under static loading conditions and aggrecan was upregulated under cyclic loading conditions. In conclusion, the fibrous component of fibrocartilage could be generated using only mechanical cues, but generation of the cartilaginous component of fibrocartilage required biologic factors in addition to mechanical cues. These studies support the hypothesis that the 3D stress environment influences cell activity and gene expression in fibrocartilage development.

  9. Normalization of Phenotypic Data from a Clinical Data Warehouse: Case Study of Heterogeneous Blood Type Data with Surprising Results.

    Science.gov (United States)

    Cimino, James J

    2015-01-01

    Clinical data warehouses often contain analogous data from disparate sources, resulting in heterogeneous formats and semantics. We have developed an approach that attempts to represent such phenotypic data in its most atomic form to facilitate aggregation. We illustrate this approach with human blood antigen typing (ABO-Rh) data drawn from the National Institutes of Health's Biomedical Translational Research Information System (BTRIS). In applying the method to actual patient data, we discovered a 2% incidence of changed blood types. We believe our approach can be applied to any institution's data to obtain comparable patient phenotypes. The actual discrepant blood type data will form the basis for a future study of the reasons for blood typing variation.

  10. Homocysteine levels are associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

    International Nuclear Information System (INIS)

    Anan, Futoshi; Yonemochi, Hidetoshi; Nakagawa, Mikiko; Saikawa, Tetsunori; Masaki, Takayuki; Takahashi, Naohiko; Yoshimatsu, Hironobu; Eshima, Nobuoki

    2007-01-01

    Elevated total plasma homocysteine (tHcy) levels and cardiovascular autonomic dysfunction are associated with a high mortality in type 2 diabetic patients. We tested the hypothesis that hyperhomocysteinemia is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The study group consisted of 17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58±5 years, high tHcy group). The control group consisted of 23 age-matched type 2 diabetic patients with normal tHcy levels (≤15 mmol/l, age 58±9 years, normal tHcy group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed 123 I-MIBG myocardial uptake values were lower (p 123 I-MIBG was higher (p 123 I-MIBG at the delayed phase. Our results demonstrate that high levels of tHcy are associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. (orig.)

  11. Precise localization of multiple epiphyseal dysplasia and pseudoachondroplasia mutations by genetic and physical mapping of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, R.G.; Cekleniak, J.A. [Jefferson Medical College, Philadelphia, PA (United States); Cohn, D.H. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others

    1994-09-01

    Multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia resulting in peripheral joint deformities and premature osteoarthritis, and pseudoachondroplasia (PSACH), a more severe disorder associated with short-limbed dwarfism, have recently been mapped to the pericentromeric region of chromosome 19. Chondrocytes from some PSACH patients accumulate lamellar deposits in the endoplasmic reticulum that are immunologically cross-reactive with aggrecan. However, neither aggrecan nor any known candidate gene maps to the EDM1/PSACH region of chromosome 19. Genetic linkage mapping in two lage families had placed the disease locus between D19S215 (19p12) and D19S212 (19p13.1), an interval of about 3.5 Mb. With at least five potentially informative cross-overs within this interval, recombination mapping at greater resolution was undertaken. From cosmids assigned to the region by fluorescence in situ hybridization and contig assembly, dinucleotide repeat tracts were identified for use as polymorphic genetic markers. Linkage data from three new dinucleotide repeat markers from cosmids mapped between D19S212 and D19S215 limit the EDM1/PSACH locus to an interval spanning approximately 2 Mb.

  12. Predicted continuum spectra of type II supernovae - LTE results

    Science.gov (United States)

    Shaviv, G.; Wehrse, R.; Wagoner, R. V.

    1985-01-01

    The continuum spectral energy distribution of the flux emerging from type II supernovae is calculated from quasi-static radiative transfer through a power-law density gradient, assuming radiative equilibrium and LTE. It is found that the Balmer jump disappears at high effective temperatures and low densities, while the spectrum resembles that of a dilute blackbody but is flatter with a sharper cutoff at the short-wavelength end. A significant UV excess is found in all models calculated. The calculation should be considered exploratory because of significant effects which are anticipated to arise from departure from LTE.

  13. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study

    NARCIS (Netherlands)

    Sluijs, van der I.; Forouhi, N.G.; Beulens, J.W.; Schouw, van der Y.T.; Feskens, E.J.M.

    2012-01-01

    Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products. Objective: The objective was to investigate the prospective association of total dairy products and different

  14. Results on an integral inequality of the opial- type | Rauf | Global ...

    African Journals Online (AJOL)

    Abstract. We obtain integral inequalities which are Opial-type inequalities, mainly by using Jensen's inequality for the case of convex function. Keywords: Integral inequalities, Opial's inequality, Jensen's inequality and convex functions ...

  15. Increased BMR in overweight and obese patients with type 2 diabetes may result from an increased fat-free mass.

    Science.gov (United States)

    Sun, Min-xian; Zhao, Shi; Mao, Hong; Wang, Zhong-jing; Zhang, Xu-yan; Yi, Lan

    2016-02-01

    The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI≤28 kg/m(2), n=99), or obese (BMI ≥28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (PBMR was significantly lower than the predicted BMR (PBMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass.

  16. Application of different types of mandible resection in combined treatment of oral cancer patient (pt.): results and complications

    International Nuclear Information System (INIS)

    Matyakin, E.G.; Uvarov, A.A.; Kropotov, M.A.; Azizjan, R.I.

    1998-01-01

    Surgery is the main part of combined treatment of advanced oral cancer. Three types of mandible resection were applied in our center. Rim mandibulectomy leads to satisfactory cosmetic and functional results, in case of segmental mandibulectomy different methods of mandible restoration are applied. Middle mandibulotomy creates the optimum access to the operation field in patients with a large primary tumor of mobile tongue and a tumor thai is posteriorly located. Aims of the study: analyse of material to estimate the results and complications in cases of application of different types of mandible resection. Conclusions: Segmental mandibulectomy should be performed if erosion of alveolar ridge is detected. Rim manidibulectomy and segmental mandibylectomy with reconstructive surgery lead to good cosmetic and functional results. Usage of mini plates in reconstruction of mandibular arch decrease the number of postoperative complications even in patients after radiation therapy. Previous radiotherapy significantly increase the risk of the postoperative osteomyelitis of mandible

  17. Platelet-rich plasma loaded in situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation.

    Science.gov (United States)

    Lee, Hye-Rim; Park, Kyung Min; Joung, Yoon Ki; Park, Ki Dong; Do, Sun Hee

    2012-11-01

    The efficacy of three-dimensional (3D) culture on the proliferation and maturation of chondrocytes seeded into a hydrogel scaffold was assessed. Three types of hydrogel were prepared for the 3D culture of primary isolated chondrocytes. Chondrocyte proliferation was assessed using a live/dead viability/cytotoxicity assay and semiquantitative RT-PCR after 3D culture in hydrogel. Cylindrical defects in the center of rat xyphoids were used for the implantation of platelet-rich plasma (PRP)/hydrogel composites. Rats were killed at day 7 postoperatively and evaluated histochemically and immunohistologically. Xyphoid chondrocytes proliferated well with time in hydrogels. In the PRP-containing hydrogels, xyphoid defects displayed early formation of chondroid matrix with massive peripheral infiltration of spindle cells. These results were consistent with Safranin-O staining for proteoglycans and immunohistochemistry for type II collagen. Gene expression analyses in vitro revealed aggrecan, type II collagen, and ChM-1 and CB1 upregulation by PRP/hydrogel. PRP/hydrogel provided a suitable environment for hyaline cartilaginous regeneration, leading to anti-inflammation by significant increase of CB1 and inhibiting vascular ingrowth via considerable upregulation of ChM-1. The results provide a valuable reference for the clinical application of hydrogel scaffolds for hyaline cartilage regeneration, as well as the use of autologous PRP to improve cellular proliferation and maturation of xyphoid repair. Copyright © 2012 Wiley Periodicals, Inc.

  18. Adherence to medicamentous therapy of type 2 diabetes mellitus: results of patient questionnaires

    Directory of Open Access Journals (Sweden)

    Elena Viktorovna Surkova

    2009-03-01

    Full Text Available Aim. To assess the frequency and character of non-compliance with medicamentous therapy of type 2 diabetes mellitus based on the results of a questionnaire study. Materials and methods. A special qiuestionnaire form was filled by 745 patients (232 men of mean age 60.3?10.4 years, duration of the disease 6.4?5.5 years and mean HbA1c level 7.7?1.1%. Results. 52.8% of the patients reported non-compliance with medication. The most frequent profile of non-compliance was the change of time and occasional omission of therapeuticdoses (42.7 and 42.2% respectively, the main cause being mere forgetfulness (71.2%. Other factors (30.8% included poor understanding of medication schedule andfears of health hazard from the following of medical advice. Patients to whom monotherapy with glibomet was prescribed (n=277 showed a lower non-compliance rate and lowerHbA1c level despite the intake of fewer daily doses than patients taking other oral hypoglycemic agents (7.0?1.0 vs 7.3?1.3%, p

  19. Methicillin-resistant Staphylococcus aureus isolates with SCCmec type V and spa types t437 or t1081 associated to discordant susceptibility results between oxacillin and cefoxitin, Central Taiwan.

    Science.gov (United States)

    Ho, Cheng-Mao; Lin, Chien-Yu; Ho, Mao-Wang; Lin, Hsiao-Chuan; Chen, Chao-Jung; Lin, Lee-Chung; Lu, Jang-Jih

    2016-12-01

    Staphylococcus aureus isolates with discordant susceptibility results between oxacillin and cefoxitin obtained using automated microbiology systems are infrequently observed. From April 2013 to December 2014, 1956 methicillin-resistant S. aureus (MRSA) and 1761 methicillin-susceptible S. aureus isolates were obtained from different patients. Forty isolates (1.1% and 2% in case of S. aureus and MRSA, respectively) with discordant susceptibility results (oxacillin susceptible and cefoxitin resistant) and carrying mecA gene were obtained. Except 2 SCCmec type IV isolates, 38 MRSA isolates were all SCCmec type V (V T or non-V T ), which were further divided into V T (n=22) and non-V T (n=16). The most common spa type in V T and non-V T isolates were t437 (n=19) and t1081 (n=13), respectively. Only 55% of patients received effective antimicrobial agents; 2 mortalities were not attributable to MRSA infection. Using standard agar dilution, 17 MRSA isolates (0.46% and 0.87% in case of S. aureus and MRSA, respectively) had oxacillin MIC in the susceptible ranges (oxacillin-susceptible MRSA [OS-MRSA]); all carried SCCmec type V (V T , n=8; non-V T , n=9). The most common spa-MLST types of OS-MRSA in V T and non-V T were t437-ST59 (n=4) and t1081-ST45 (n=7), respectively. Concomitant testing by both cefoxitin- and oxacillin-based methods is a practical strategy for OS-MRSA detection in the clinical laboratories. Continuous monitoring of OS-MRSA isolates is necessary to elucidate their impact in clinical infectious diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Early Intra-Articular Complement Activation in Ankle Fractures

    Directory of Open Access Journals (Sweden)

    Hagen Schmal

    2014-01-01

    Full Text Available Cytokine regulation possibly influences long term outcome following ankle fractures, but little is known about synovial fracture biochemistry. Eight patients with an ankle dislocation fracture were included in a prospective case series and matched with patients suffering from grade 2 osteochondritis dissecans (OCD of the ankle. All fractures needed external fixation during which joint effusions were collected. Fluid analysis was done by ELISA measuring aggrecan, bFGF, IL-1β, IGF-1, and the complement components C3a, C5a, and C5b-9. The time periods between occurrence of fracture and collection of effusion were only significantly associated with synovial aggrecan and C5b-9 levels (P<0.001. Furthermore, synovial expressions of both proteins correlated with each other (P<0.001. Although IL-1β expression was relatively low, intra-articular levels correlated with C5a (P<0.01 and serological C-reactive protein concentrations 2 days after surgery (P<0.05. Joint effusions were initially dominated by neutrophils, but the portion of monocytes constantly increased reaching 50% at day 6 after fracture (P<0.02. Whereas aggrecan and IL-1β concentrations were not different in fracture and OCD patients, bFGF, IGF-1, and all complement components were significantly higher concentrated in ankle joints with fractures (P<0.01. Complement activation and inflammatory cell infiltration characterize the joint biology following acute ankle fractures.

  1. Test results on the dynamic testing of expansion type concrete anchors

    International Nuclear Information System (INIS)

    Barron, B.; Rice, R.; Stephen, R.M.

    1974-12-01

    Tests were performed to determine the structural response of commercially available expansion type anchors for the FFTF when subjected to dynamic loadings similar to machine vibrations and earthquakes. The specimens were subjected to tension, shear, and combined shear-tension loads

  2. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  3. [Deleterious Results of Safety Seeking Behaviours in Panic Disorder: Polydipsia and Diabetes Mellitus Type 2].

    Science.gov (United States)

    Kurt, Emel; Karabaş, Özer; Yorguner, Neşe; Wurz, Axel; Topçuoğlu, Volkan

    2016-01-01

    Panic disorder is an anxiety disorder that involves recurrent panic attacks, which emerge when a harmless stimulus is interpreted as "catastrophic". In an attempt to avoid the panic attack or prevent confrontation, the patient exhibits a dysfunctional attitude and behavior, such as evasion and safety-seeking behavior (SSB). Dysfunctional behavior leads to an increase in the recurrence of panic attacks and affects the patient's life in a negative way. According to the cognitive behavioral therapy model, SSB contributes to the continuation of unrealistic beliefs (e.g. physical experiences) regarding and prevents the patient from grasping new information that may potentially contradict the unrealistic cognitions. In this paper, we present a case with a primary diagnosis of panic disorder. Interestingly, this patient developed diabetes mellitus (DM) type 2 and psychogenic polydipsia (PPD) as a consequence of his SSB. PPD is a common occurrence in patients with psychiatric disorders, especially in schizophrenia. Up to now, no case of a panic disorder with either DM or PPD has been reported in the literature. While it is accepted that major depression poses a risk for DM type 2, panic disorder may also increase this risk. Treatment of the panic disorder with cognitive behavioral therapy (CBT) resulted in improvement of PPD and DM type 2. In conclusion, the role of SSB in medical disorders accompanied by psychiatric disorders should be kept in mind when treating these patients.

  4. Remarks on the Liouville type results for the compressible Navier–Stokes equations in RN

    International Nuclear Information System (INIS)

    Chae, Dongho

    2012-01-01

    In this paper, we prove Liouville type result for the stationary solutions to the compressible Navier–Stokes equations (NS) and the compressible Navier–Stokes–Poisson (NSP) equations and in R N , N ≥ 2. Assuming suitable integrability and the uniform boundedness conditions for the solutions we are led to the conclusion that v = 0. In the case of (NS) we deduce that the similar integrability conditions imply v = 0 and ρ = constant on R N . This shows that if we impose the the non-vacuum boundary condition at spatial infinity for (NS), v → 0 and ρ → ρ ∞ > 0, then v = 0, ρ = ρ ∞ are the solutions

  5. Mechanoactive scaffold induces tendon remodeling and expression of fibrocartilage markers.

    Science.gov (United States)

    Spalazzi, Jeffrey P; Vyner, Moira C; Jacobs, Matthew T; Moffat, Kristen L; Lu, Helen H

    2008-08-01

    Biological fixation of soft tissue-based grafts for anterior cruciate ligament (ACL) reconstruction poses a major clinical challenge. The ACL integrates with subchondral bone through a fibrocartilage enthesis, which serves to minimize stress concentrations and enables load transfer between two distinct tissue types. Functional integration thus requires the reestablishment of this fibrocartilage interface on reconstructed ACL grafts. We designed and characterized a novel mechanoactive scaffold based on a composite of poly-alpha-hydroxyester nanofibers and sintered microspheres; we then used the scaffold to test the hypothesis that scaffold-induced compression of tendon grafts would result in matrix remodeling and the expression of fibrocartilage interface-related markers. Histology coupled with confocal microscopy and biochemical assays were used to evaluate the effects of scaffold-induced compression on tendon matrix collagen distribution, cellularity, proteoglycan content, and gene expression over a 2-week period. Scaffold contraction resulted in over 15% compression of the patellar tendon graft and upregulated the expression of fibrocartilage-related markers such as Type II collagen, aggrecan, and transforming growth factor-beta3 (TGF-beta3). Additionally, proteoglycan content was higher in the compressed tendon group after 1 day. The data suggest the potential of a mechanoactive scaffold to promote the formation of an anatomic fibrocartilage enthesis on tendon-based ACL reconstruction grafts.

  6. Do sediment type and test durations affect results of laboratory-based, accelerated testing studies of permeable pavement clogging?

    Science.gov (United States)

    Nichols, Peter W B; White, Richard; Lucke, Terry

    2015-04-01

    Previous studies have attempted to quantify the clogging processes of Permeable Interlocking Concrete Pavers (PICPs) using accelerated testing methods. However, the results have been variable. This study investigated the effects that three different sediment types (natural and silica), and different simulated rainfall intensities, and testing durations had on the observed clogging processes (and measured surface infiltration rates) of laboratory-based, accelerated PICP testing studies. Results showed that accelerated simulated laboratory testing results are highly dependent on the type, and size of sediment used in the experiments. For example, when using real stormwater sediment up to 1.18 mm in size, the results showed that neither testing duration, nor stormwater application rate had any significant effect on PICP clogging. However, the study clearly showed that shorter testing durations generally increased clogging and reduced the surface infiltration rates of the models when artificial silica sediment was used. Longer testing durations also generally increased clogging of the models when using fine sediment (<300 μm). Results from this study will help researchers and designers better anticipate when and why PICPs are susceptible to clogging, reduce maintenance and extend the useful life of these increasingly common stormwater best management practices. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Patch test results of hand eczema patients : relation to clinical types

    NARCIS (Netherlands)

    Boonstra, M B; Christoffers, W A; Coenraads, P J; Schuttelaar, M L A

    BACKGROUND: Allergic contact dermatitis is a well-known cause of hand eczema, although the influence of contact allergens on different clinical types of hand eczema remains still unclear. OBJECTIVE: To identify most common positive tested allergens among hand eczema patients and to define the

  8. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Manuel Mata

    2017-01-01

    Full Text Available Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI. The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  9. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study.

    Science.gov (United States)

    Mata, Manuel; Milian, Lara; Oliver, Maria; Zurriaga, Javier; Sancho-Tello, Maria; de Llano, Jose Javier Martin; Carda, Carmen

    2017-01-01

    Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo , but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs) to regenerate cartilage in vitro and in vivo . hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  10. Relationship between socioeconomic status and type 2 diabetes: results from Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012

    OpenAIRE

    Hwang, Jongnam; Shon, Changwoo

    2014-01-01

    Objective To examine the relationship between socioeconomic status (SES) and type 2 diabetes using the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012. Design A pooled sample cross-sectional study. Setting A nationally representative population survey data. Participants A total of 14 330 individuals who participated in the KNHANES 2010–2012 were included in our analysis. Primary outcome Prevalence of type 2 diabetes. Results The relationship between SES and type 2 d...

  11. Improving the results of transarterial embolization of type 2 endoleaks with the embolic polymer Onyx.

    Science.gov (United States)

    Wojtaszek, Mikolaj; Wnuk, Emilia; Maciag, Rafal; Solonynko, Bohdan; Korzeniowski, Krzysztof; Lamparski, Krzysztof; Rowinski, Olgierd

    2016-01-01

    Type 2 endoleaks (T2E) occur in 10 to 20% of patients after endovascular abdominal aortic aneurysm repair (EVAR) and remain a significant clinical issue. To evaluate the efficacy and clinical outcomes of transarterial treatment of persistent type II endoleaks after EVAR using the liquid embolic Onyx. From February 2012 to August 2015 transarterial T2E embolization was attempted in 22 patients (21 men, median age: 73, range: 62-88 years). Indications for treatment included an increase in the diameter of the aneurysm sac above 5 mm and a persistent endoleak observed for more than 6 months. Mean time from EVAR to endoleak treatment was 43 months (range: 2-125 months). Primary technical success was achieved in 17 (77.3%) patients and secondary technical success in 81.8%, with 0% in-hospital mortality. The mean procedure time was 95 ±48 min, with an average fluoroscopy time of 54 ±25 min. The mean amount of Onyx used was 7.5 ±6.6 ml. Clinical success was seen in 17/21 patients with follow-up imaging (80.9%). Mean follow-up time was 17 months (range: 3-38 months). Onyx has been shown to effectively stabilize previous aneurysm growth as a result of the T2E in the majority of our patients. Transarterial embolization of T2E can be significantly improved as compared to previously reported results by using liquid embolic polymers such as Onyx.

  12. Use of the LUS in sequence allele designations to facilitate probabilistic genotyping of NGS-based STR typing results.

    Science.gov (United States)

    Just, Rebecca S; Irwin, Jodi A

    2018-05-01

    Some of the expected advantages of next generation sequencing (NGS) for short tandem repeat (STR) typing include enhanced mixture detection and genotype resolution via sequence variation among non-homologous alleles of the same length. However, at the same time that NGS methods for forensic DNA typing have advanced in recent years, many caseworking laboratories have implemented or are transitioning to probabilistic genotyping to assist the interpretation of complex autosomal STR typing results. Current probabilistic software programs are designed for length-based data, and were not intended to accommodate sequence strings as the product input. Yet to leverage the benefits of NGS for enhanced genotyping and mixture deconvolution, the sequence variation among same-length products must be utilized in some form. Here, we propose use of the longest uninterrupted stretch (LUS) in allele designations as a simple method to represent sequence variation within the STR repeat regions and facilitate - in the nearterm - probabilistic interpretation of NGS-based typing results. An examination of published population data indicated that a reference LUS region is straightforward to define for most autosomal STR loci, and that using repeat unit plus LUS length as the allele designator can represent greater than 80% of the alleles detected by sequencing. A proof of concept study performed using a freely available probabilistic software demonstrated that the LUS length can be used in allele designations when a program does not require alleles to be integers, and that utilizing sequence information improves interpretation of both single-source and mixed contributor STR typing results as compared to using repeat unit information alone. The LUS concept for allele designation maintains the repeat-based allele nomenclature that will permit backward compatibility to extant STR databases, and the LUS lengths themselves will be concordant regardless of the NGS assay or analysis tools

  13. Raman and infrared results on YBa2Cu3Osub(7-x) type materials

    International Nuclear Information System (INIS)

    Burns, G.; Dacol, F.H.; Freitas, P.; Plaskett, T.S.; Koenig, W.

    1987-01-01

    We report both Raman and infrared results on the same semiconducting YBa 2 Cu 3 Osub(7-x) material. With the appropriate heat treatment, this material can be reversibly changed from an orthorhombic superconductor x approx. = 0.0) to a semiconductor (x > 0.5). In the semiconducting material it is easier to measure the phonon features using either technique, and we observe almost the number of modes allowed. By simultaneously considering the modes observed by both techniques, using group theory to sort out the modes in both phases, and using projection operators to determine the symmetry adapted vectors, we arrive at an understanding of some of the modes. We find few differences when comparing our results to other measurements in the superconducting phase. The two general conclusions that we arrive at are: 1) splittings of the modes due to lowering the symmetry from tetragonal to the superconducting orthorhombic phase are not observed; 2) no frequency renormalizations, of the type that have been discussed theoretically, are observed. (author)

  14. Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.

    Science.gov (United States)

    Smith, L T; Wertelecki, W; Milstone, L M; Petty, E M; Seashore, M R; Braverman, I M; Jenkins, T G; Byers, P H

    1992-08-01

    Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules.

  15. Type inference for correspondence types

    DEFF Research Database (Denmark)

    Hüttel, Hans; Gordon, Andy; Hansen, Rene Rydhof

    2009-01-01

    We present a correspondence type/effect system for authenticity in a π-calculus with polarized channels, dependent pair types and effect terms and show how one may, given a process P and an a priori type environment E, generate constraints that are formulae in the Alternating Least Fixed......-Point (ALFP) logic. We then show how a reasonable model of the generated constraints yields a type/effect assignment such that P becomes well-typed with respect to E if and only if this is possible. The formulae generated satisfy a finite model property; a system of constraints is satisfiable if and only...... if it has a finite model. As a consequence, we obtain the result that type/effect inference in our system is polynomial-time decidable....

  16. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.

    Science.gov (United States)

    Seehusen, Frauke; Al-Azreg, Seham A; Raddatz, Barbara B; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.

  17. The VIRTUE Registry of type B thoracic dissections--study design and early results

    DEFF Research Database (Denmark)

    2011-01-01

    Endovascular procedures for repair of Type B aortic dissection have become increasingly common and are often considered to be first line therapy for acute complicated dissections. The long term durability of these repairs is largely undefined.......Endovascular procedures for repair of Type B aortic dissection have become increasingly common and are often considered to be first line therapy for acute complicated dissections. The long term durability of these repairs is largely undefined....

  18. Participants' preference for type of leaflet used to feed back the results of a randomised trial: a survey

    Directory of Open Access Journals (Sweden)

    Houston Helen

    2010-12-01

    Full Text Available Abstract Background Hundreds of thousands of volunteers take part in medical research, but many will never hear from researchers about what the study revealed. There is a growing demand for the results of randomised trials to be fed back to research participants both for ethical research practice and for ensuring their co-operation in a trial. This study aims to determine participants' preferences for type of leaflet (short versus long used to summarise the findings of a randomised trial; and to test whether certain characteristics explained participants' preferences. Methods 553 participants in a randomised trial about General Practitioners' access to Magnetic Resonance Imaging for patients presenting with suspected internal derangement of the knee were asked in the final follow-up questionnaire whether they would like to be fed back the results of the trial. Participants who agreed to this were included in a postal questionnaire survey asking about their preference, if any, between a short and a long leaflet and what it was about the leaflet that they preferred. Multinomial logistic regression was used to test whether certain demographics of responding participants along with treatment group explained whether a participant had a preference for type of leaflet or no preference. Results Of the participants who returned the final follow-up questionnaire, 416 (88% agreed to receive the results of the trial. Subsequently 132 (32% participants responded to the survey. Most participants preferred the longer leaflet (55% and the main reasons for this were the use of technical information (94% and diagrams (89%. There was weak evidence to suggest that gender might explain whether participants have a preference for type of leaflet or not (P = 0.084. Conclusions Trial participants want to receive feed back about the results and appear to prefer a longer leaflet. Males and females might require information to be communicated to them differently and should

  19. The progress and results of a demonstration test of a cavern-type disposal facility

    International Nuclear Information System (INIS)

    Akiyama, Yoshihiro; Terada, Kenji; Oda, Nobuaki; Yada, Tsutomu; Nakajima, Takahiro

    2011-01-01

    The cavern-type disposal facilities for low-level waste (LLW) with relatively high radioactivity levels mainly generated from power reactor decommissioning and for part of transuranic (TRU) waste mainly from spent fuel reprocessing are designed to be constructed in a cavern 50 to 100 meters below ground, and to employ an engineered barrier system (EBS) of a combination of bentonite and cement materials in Japan. In order to advance the feasibility study for these disposal, a government-commissioned research project named Demonstration Test of Cavern-Type Disposal Facility started in fiscal 2005, and since fiscal 2007 a full-scale mock-up test facility has been constructed under actual subsurface environment. The main objective of the test is to establish construction methodology and procedures which ensure the required quality of the EBS on-site. By fiscal 2009 some parts of the facility have been constructed, and the test has demonstrated both practicability of the construction and achievement of the quality. They are respectively taken as low-permeability of less than 5x10 13 m/s and low-diffusivity of less than 1x10 -12 m 2 /s at the time of completion of construction. This paper covers the project outline and the test results obtained by the construction of some parts of a bentonite and cement materials. (author)

  20. Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture

    DEFF Research Database (Denmark)

    Mehlhorn, A T; Schmal, H; Kaiser, S

    2006-01-01

    cultured in osteogenic medium after TGF-beta-mediated chondroinduction. Gene expression of col2a1, aggrecan, COMP, alkaline phosphatase (AP), and correlating protein synthesis was analyzed. After short-term stimulation with TGF-beta, MSCs maintained a chondrogenic phenotype. Chondrogenic gene expression...

  1. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

    Full Text Available Abstract Background Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don’s chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids that is in clinical use in Germany. Methods Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. Results After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids

  2. Cell type-dependent induction of DNA damage by 1800 MHz radiofrequency electromagnetic fields does not result in significant cellular dysfunctions.

    Directory of Open Access Journals (Sweden)

    Shanshan Xu

    Full Text Available BACKGROUND: Although IARC clarifies radiofrequency electromagnetic fields (RF-EMF as possible human carcinogen, the debate on its health impact continues due to the inconsistent results. Genotoxic effect has been considered as a golden standard to determine if an environmental factor is a carcinogen, but the currently available data for RF-EMF remain controversial. As an environmental stimulus, the effect of RF-EMF on cellular DNA may be subtle. Therefore, more sensitive method and systematic research strategy are warranted to evaluate its genotoxicity. OBJECTIVES: To determine whether RF-EMF does induce DNA damage and if the effect is cell-type dependent by adopting a more sensitive method γH2AX foci formation; and to investigate the biological consequences if RF-EMF does increase γH2AX foci formation. METHODS: Six different types of cells were intermittently exposed to GSM 1800 MHz RF-EMF at a specific absorption rate of 3.0 W/kg for 1 h or 24 h, then subjected to immunostaining with anti-γH2AX antibody. The biological consequences in γH2AX-elevated cell type were further explored with comet and TUNEL assays, flow cytometry, and cell growth assay. RESULTS: Exposure to RF-EMF for 24 h significantly induced γH2AX foci formation in Chinese hamster lung cells and Human skin fibroblasts (HSFs, but not the other cells. However, RF-EMF-elevated γH2AX foci formation in HSF cells did not result in detectable DNA fragmentation, sustainable cell cycle arrest, cell proliferation or viability change. RF-EMF exposure slightly but not significantly increased the cellular ROS level. CONCLUSIONS: RF-EMF induces DNA damage in a cell type-dependent manner, but the elevated γH2AX foci formation in HSF cells does not result in significant cellular dysfunctions.

  3. Transforming growth factor β-induced expression of chondroitin sulfate proteoglycans is mediated through non-Smad signaling pathways.

    Science.gov (United States)

    Jahan, Naima; Hannila, Sari S

    2015-01-01

    The expression of chondroitin sulfate proteoglycans (CSPGs) by reactive astrocytes is a major factor contributing to glial scarring and regenerative failure after spinal cord injury, but the molecular mechanisms underlying CSPG expression remain largely undefined. One contributing factor is transforming growth factor β (TGFβ), which is upregulated after injury and has been shown to induce expression of CSPGs in vitro. TGFβ typically mediates its effects through the Smad2/3 signaling pathway, and it has been suggested that this pathway is responsible for CSPG expression. However, there is evidence that TGFβ can also activate non-Smad signaling pathways. In this study, we report that TGFβ-induced expression of three different CSPGs--neurocan, brevican, and aggrecan--is mediated through non-Smad signaling pathways. We observed significant increases in TGFβ-induced expression of neurocan, brevican, and aggrecan following siRNA knockdown of Smad2 or Smad4, which indicates that Smad signaling is not required for the expression of these CSPGs. In addition, we show that neurocan, aggrecan, and brevican levels are significantly reduced when TGFβ is administered in the presence of either the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin, but not the MEK1/2 inhibitor U0126. This suggests that TGFβ mediates this effect through non-Smad-dependent activation of the PI3K-Akt-mTOR signaling pathway, and targeting this pathway may therefore be an effective means of reducing CSPG expression in the injured CNS. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels.

    Science.gov (United States)

    Nicodemus, G D; Skaalure, S C; Bryant, S J

    2011-02-01

    While designing poly(ethylene glycol) hydrogels with high moduli suitable for in situ placement is attractive for cartilage regeneration, the impact of a tighter crosslinked structure on the organization and deposition of the matrix is not fully understood. The objectives of this study were to characterize the composition and spatial organization of new matrix as a function of gel crosslinking and study its impact on chondrocytes in terms of anabolic and catabolic gene expression and catabolic activity. Bovine articular chondrocytes were encapsulated in hydrogels with three crosslinking densities (compressive moduli 60, 320 and 590 kPa) and cultured for 25 days. Glycosaminoglycan production increased with culture time and was greatest in the gels with lowest crosslinking. Collagens II and VI, aggrecan, link protein and decorin were localized to pericellular regions in all gels, but their presence decreased with increasing gel crosslinking. Collagen II and aggrecan expression were initially up-regulated in gels with higher crosslinking, but increased similarly up to day 15. Matrix metalloproteinase (MMP)-1 and MMP-13 expression were elevated (∼25-fold) in gels with higher crosslinking throughout the study, while MMP-3 was unaffected by gel crosslinking. The presence of aggrecan and collagen degradation products confirmed MMP activity. These findings indicate that chondrocytes synthesized the major cartilage components within PEG hydrogels, however, gel structure had a significant impact on the composition and spatial organization of the new tissue and on how chondrocytes responded to their environment, particularly with respect to their catabolic expression. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Participants' preference for type of leaflet used to feed back the results of a randomised trial: a survey.

    Science.gov (United States)

    Brealey, Stephen; Andronis, Lazaros; Dennis, Laura; Atwell, Christine; Bryan, Stirling; Coulton, Simon; Cox, Helen; Cross, Ben; Fylan, Fiona; Garratt, Andrew; Gilbert, Fiona; Gillan, Maureen; Hendry, Maggie; Hood, Kerenza; Houston, Helen; King, David; Morton, Veronica; Robling, Michael; Russell, Ian; Wilkinson, Clare

    2010-12-01

    Hundreds of thousands of volunteers take part in medical research, but many will never hear from researchers about what the study revealed. There is a growing demand for the results of randomised trials to be fed back to research participants both for ethical research practice and for ensuring their co-operation in a trial. This study aims to determine participants' preferences for type of leaflet (short versus long) used to summarise the findings of a randomised trial; and to test whether certain characteristics explained participants' preferences. 553 participants in a randomised trial about General Practitioners' access to Magnetic Resonance Imaging for patients presenting with suspected internal derangement of the knee were asked in the final follow-up questionnaire whether they would like to be fed back the results of the trial. Participants who agreed to this were included in a postal questionnaire survey asking about their preference, if any, between a short and a long leaflet and what it was about the leaflet that they preferred. Multinomial logistic regression was used to test whether certain demographics of responding participants along with treatment group explained whether a participant had a preference for type of leaflet or no preference. Of the participants who returned the final follow-up questionnaire, 416 (88%) agreed to receive the results of the trial. Subsequently 132 (32%) participants responded to the survey. Most participants preferred the longer leaflet (55%) and the main reasons for this were the use of technical information (94%) and diagrams (89%). There was weak evidence to suggest that gender might explain whether participants have a preference for type of leaflet or not (P = 0.084). Trial participants want to receive feed back about the results and appear to prefer a longer leaflet. Males and females might require information to be communicated to them differently and should be the focus of further research. The trial is registered

  6. Radiation therapy for wet type age-related macular degeneration. Long term follow-up results

    Energy Technology Data Exchange (ETDEWEB)

    Sasai, Keisuke; Hiraoka, Masahiro; Mandai, Michiyo; Takahashi, Masayo; Honda, Yoshihito [Kyoto Univ. (Japan). Faculty of Medicine

    1998-12-01

    Between April, 1994 and July, 1995, 33 patients with occult type choroidal neovascularization (CNV) with or without the classical type CNV of the wet type age-related macular degeneration ARMD were treated with radiation therapy (10 Gy/5 fx/1 week or 20 Gy/10 fx/2 weeks). This phase I/II study showed that radiation therapy seems to be useful for CNV during the first 12 months. Some eyes which initially showed good response to irradiation began to lose their visual acuity. However, the dose of 20 Gy in 10 fractions seemed useful to maintain the visual acuity better than 0.1 in this long term follow-up study (24 months). (author)

  7. Comparison of rosuvastatin and atorvastatin for lipid lowering in patients with type 2 diabetes mellitus: results from the URANUS study

    Directory of Open Access Journals (Sweden)

    Berne Christian

    2005-06-01

    Full Text Available Abstract Objective The Use of Rosuvastatin versus Atorvastatin iN type 2 diabetes mellitUS (URANUS study compared rosuvastatin with atorvastatin for the reduction of low-density lipoprotein cholesterol (LDL-C in patients with type 2 diabetes. Methods After a 6-week dietary run-in, patients aged ≥ 18 years with type 2 diabetes and LDL-C ≥ 3.3 mmol/L were randomised to double-blind treatment with rosuvastatin 10 mg (n = 232 or atorvastatin 10 mg (n = 233 for 4 weeks. Doses were then titrated up to a maximum of rosuvastatin 40 mg or atorvastatin 80 mg over 12 weeks to achieve the 1998 European LDL-C goal ( Results Rosuvastatin reduced LDL-C levels significantly more than atorvastatin during the fixed-dose and titration periods (p Conclusion At the start dose and following dose titration, rosuvastatin was significantly more effective than atorvastatin at reducing LDL-C and achieving European LDL-C goals in patients with type 2 diabetes.

  8. Abdominal visceral fat accumulation is associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

    International Nuclear Information System (INIS)

    Anan, Futoshi; Masaki, Takayuki; Takahashi, Naohiko; Yoshimatsu, Hironobu; Yonemochi, Hidetoshi; Nakagawa, Mikiko; Saikawa, Tetsunori; Eshima, Nobuoki

    2007-01-01

    We tested the hypothesis that increased abdominal visceral accumulation (VFA) is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The study group consisted of 24 type 2 diabetic patients with high VFA (≥100 cm 2 , age 60 ± 8 years, high VFA group). The control group consisted of 19 age-matched type 2 diabetic patients with normal VFA ( 2 , age 60 ± 7 years, normal VFA group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed 123 I-MIBG myocardial uptake values were lower (p 123 I-MIBG was higher (p 123 I-MIBG during the delayed phase. Our results demonstrate that the level of VFA is associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. (orig.)

  9. Macro creatine kinases: results of isoenzyme electrophoresis and differentiation of the immunoglobulin-bound type by radioassay

    International Nuclear Information System (INIS)

    Bohner, J.; Stein, W.; Steinhart, R.; Wurzburg, U.; Eggstein, M.

    1982-01-01

    In 2.9% of sera from 1253 unselected patients we detected two different types of macromolecular creatine kinases (CK;EC 2.7.3.2). One macro type was represented by immunoglobulin-linked CK; in sera containing macro CK-BB isoenzyme, 125 I-labeled CK-BB was bound with high affinity to the immunoglobulin fraction. Furthermore, during electrophoresis, macro CK-BB mostly migrated between CK-MB and CK-MM, and was fixed to Protein A from Staphlococcus aureus. We therefore propose radioelectrophoresis as a specific, highly sensitive, and simple method for detecting this type of macro CK. This form occurs predominantly in elderly women, is not correlated to any specific disease, and persists in blood over a long period of time. In contrast, a second type (macro-CK type 2) never bound radiolabeled CK isoenzymes, and was not adsorbed to protein A. Electrophoretic migration of this macro-CK type 2 was generally cathodic to CK-MM. We observed this type in severely ill patients, frequently those suffering from malignant tumors. Clinical observations and biochemical data suggest that macro-CK type 2 is of mitochondrial origin

  10. Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

    Science.gov (United States)

    Arakaki, Kazunobu; Kitamura, Nobuto; Kurokawa, Takayuki; Onodera, Shin; Kanaya, Fuminori; Gong, Jian-Ping; Yasuda, Kazunori

    2011-02-01

    We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

  11. Sensitivity analysis for thermo-hydraulics model of a Westinghouse type PWR. Verification of the simulation results

    Energy Technology Data Exchange (ETDEWEB)

    Farahani, Aref Zarnooshe [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Dept. of Nuclear Engineering, Science and Research Branch; Yousefpour, Faramarz [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Hoseyni, Seyed Mohsen [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Dept. of Basic Sciences; Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Young Researchers and Elite Club

    2017-07-15

    Development of a steady-state model is the first step in nuclear safety analysis. The developed model should be qualitatively analyzed first, then a sensitivity analysis is required on the number of nodes for models of different systems to ensure the reliability of the obtained results. This contribution aims to show through sensitivity analysis, the independence of modeling results to the number of nodes in a qualified MELCOR model for a Westinghouse type pressurized power plant. For this purpose, and to minimize user error, the nuclear analysis software, SNAP, is employed. Different sensitivity cases were developed by modification of the existing model and refinement of the nodes for the simulated systems including steam generators, reactor coolant system and also reactor core and its connecting flow paths. By comparing the obtained results to those of the original model no significant difference is observed which is indicative of the model independence to the finer nodes.

  12. Polarimetric survey of main-belt asteroids⋆. III. Results for 33 X-type objects

    Science.gov (United States)

    Cañada-Assandri, M.; Gil-Hutton, R.; Benavidez, P.

    2012-06-01

    Aims: We present results of a polarimetric survey of main-belt asteroids at Complejo Astronómico El Leoncito (Casleo), San Juan, Argentina. The aims of this survey are to increase the database of asteroid polarimetry, to estimate diversity in polarimetric properties of asteroids that belong to different taxonomic classes, and to search for objects that exhibit anomalous polarimetric properties. Methods: The data were obtained with the Torino and CASPROF polarimeters at the 2.15 m telescope. The Torino polarimeter is an instrument that allows the simultaneous measurement of polarization in five different bands, and the CASPROF polarimeter is a two-hole aperture polarimeter with rapid modulation. Results: The survey began in 2003, and up to 2009 data of a sample of more than 170 asteroids were obtained. In this paper the results for 33 X-type objects are presented, several of them are being polarimetrically observed for the first time. Using these data we found polarization curves and polarimetric parameters for different groups among this taxonomic class and that there are objects with very different albedo in the sub-classes of the X taxonomic complex. Based on observations carried out at the Complejo Astronómico El Leoncito, operated under agreement between the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina and the National Universities of La Plata, Córdoba, and San Juan.Table 1 is only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/542/A11

  13. Experimental study of tissue-engineered cartilage allograft with RNAi chondrocytes in vivo

    Directory of Open Access Journals (Sweden)

    Wang ZH

    2014-05-01

    Full Text Available Zhenghui Wang,1 Xiaoli Li,2 Xi-Jing He,3 Xianghong Zhang,1 Zhuangqun Yang,4 Min Xu,1 Baojun Wu,1 Junbo Tu,5 Huanan Luo,1 Jing Yan11Department of Otolaryngology – Head and Neck Surgery, 2Department of Dermatology, 3Department of Orthopedics, The Second Hospital, Xi’an Jiaotong University, 4Department of Plastic and Burns Surgery, The First Hospital, Xi’an Jiaotong University, 5Department of Oral and Maxillofacial Plastic Surgery, The Stomatological Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaPurpose: To determine the effects of RNA interference (RNAi on chondrocyte proliferation, function, and immunological rejection after allogenic tissue-engineered cartilage transplantation within bone matrix gelatin scaffolds.Methods: Seven million rat normal and RNAi chondrocytes were harvested and separately composited with fibrin glue to make the cell suspension, and then transplanted subcutaneously into the back of Sprague Dawley rats after being cultured for 10 days in vitro. Untransplanted animals served as the control group. The allograft and immunological response were examined at 1, 2, 4, 8, and 12 months postoperatively with hematoxylin and eosin histochemical staining, immunohistochemical staining (aggrecan, type II collagen, class I and II major histocompatibility complex, and flow cytometry for peripheral blood cluster of differentiation 4+ (CD4+ and CD8+ T-cells.Results: There was no infection or death in the rats except one, which died in the first week. Compared to the control group, the RNAi group had fewer eukomonocytes infiltrated, which were only distributed around the graft. The ratio of CD4+/CD8+ T-cells in the RNAi group was significantly lower than the normal one (P<0.05. There were many more positively stained chondrocytes and positively stained areas around the cells in the RNAi group, which were not found in the control group.Conclusion: The aggrecanase-1 and aggrecanase-2 RNAi for chondrocytes

  14. Hypoxia-inducible factor (HIF)-1α and CCN2 form a regulatory circuit in hypoxic nucleus pulposus cells: CCN2 suppresses HIF-1α level and transcriptional activity.

    Science.gov (United States)

    Tran, Cassie M; Fujita, Nobuyuki; Huang, Bau-Lin; Ong, Jessica R; Lyons, Karen M; Shapiro, Irving M; Risbud, Makarand V

    2013-05-03

    The objective of the study was to investigate if hypoxia-inducible factor (HIF)-1α and connective tissue growth factor (CCN2) form a regulatory network in hypoxic nucleus pulposus (NP) cells. A decrease in CCN2 expression and proximal promoter activity was observed in NP cells after hypoxic culture. Analysis of both human and mouse CCN2 promoters using the JASPAR core database revealed the presence of putative hypoxia response elements. Transfection experiments showed that both promoter activities and CCN2 expression decreases in hypoxia in a HIF-1α-dependent fashion. Interestingly, deletion analysis and mutation of the hypoxia responsive elements individually or in combination resulted in no change in promoter activity in response to hypoxia or in response to HIF-1α, suggesting an indirect mode of regulation. Notably, silencing of endogenous CCN2 increased HIF-1α levels and its target gene expression, suggesting a role for CCN2 in controlling basal HIF-1α levels. On the other hand, treatment of cells with rCCN2 resulted in a decrease in the ability of HIF-1α transactivating domain to recruit co-activators and diminished target gene expression. Last, knockdown of CCN2 in NP cells results in a significant decrease in GAG synthesis and expression of AGGRECAN and COLLAGEN II. Immunohistochemical staining of intervertebral discs of Ccn2 null embryos shows a decrease in aggrecan. These findings reveal a negative feedback loop between CCN2 and HIF-1α in NP cells and demonstrate a role for CCN2 in maintaining matrix homeostasis in this tissue.

  15. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    Science.gov (United States)

    Piai, Juliana Francis; da Silva, Marta Alves; Martins, Albino; Torres, Ana Bela; Faria, Susana; Reis, Rui L.; Muniz, Edvani Curti; Neves, Nuno M.

    2017-05-01

    Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O3 exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  16. Forensic typing of autosomal SNPs with a 29 SNP-multiplex--results of a collaborative EDNAP exercise.

    Science.gov (United States)

    Sanchez, J J; Børsting, C; Balogh, K; Berger, B; Bogus, M; Butler, J M; Carracedo, A; Court, D Syndercombe; Dixon, L A; Filipović, B; Fondevila, M; Gill, P; Harrison, C D; Hohoff, C; Huel, R; Ludes, B; Parson, W; Parsons, T J; Petkovski, E; Phillips, C; Schmitter, H; Schneider, P M; Vallone, P M; Morling, N

    2008-06-01

    We report the results of an inter-laboratory exercise on typing of autosomal single nucleotide polymorphisms (SNP) for forensic genetic investigations in crime cases. The European DNA Profiling Group (EDNAP), a working group under the International Society for Forensic Genetics (ISFG), organised the exercise. A total of 11 European and one US forensic genetic laboratories tested a subset of a 52 SNP-multiplex PCR kit developed by the SNPforID consortium. The 52 SNP-multiplex kit amplifies 52 DNA fragments with 52 autosomal SNP loci in one multiplex PCR. The 52 SNPs are detected in two separate single base extension (SBE) multiplex reactions with 29 and 23 SNPs, respectively, using SNaPshot kit, capillary electrophoresis and multicolour fluorescence detection. For practical reasons, only the 29 SBE multiplex reaction was carried out by the participating laboratories. A total of 11 bloodstains on FTA cards including a sample of poor quality and a negative control were sent to the laboratories together with the essential reagents for the initial multiplex PCR and the multiplex SBE reaction. The total SNP locus dropout rate was 2.8% and more than 50% of the dropouts were observed with the poor quality sample. The overall rate of discrepant SNP allele assignments was 2.0%. Two laboratories reported 60% of all the discrepancies. Two laboratories reported all 29 SNP alleles in all 10 positive samples correctly. The results of the collaborative exercise were surprisingly good and demonstrate that SNP typing with SBE, capillary electrophoresis and multicolour detection methods can be developed for forensic genetics.

  17. Chondrocyte behavior on nanostructured micropillar polypropylene and polystyrene surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Prittinen, Juha [Department of Applied Physics, University of Eastern Finland, Kuopio (Finland); Jiang, Yu [Department of Chemistry, University of Eastern Finland, Joensuu (Finland); Ylärinne, Janne H. [Department of Applied Physics, University of Eastern Finland, Kuopio (Finland); Pakkanen, Tapani A. [Department of Chemistry, University of Eastern Finland, Joensuu (Finland); Lammi, Mikko J., E-mail: mikko.lammi@uef.fi [Department of Applied Physics, University of Eastern Finland, Kuopio (Finland); Qu, Chengjuan [Department of Applied Physics, University of Eastern Finland, Kuopio (Finland)

    2014-10-01

    This study was aimed to investigate whether patterned polypropylene (PP) or polystyrene (PS) could enhance the chondrocytes' extracellular matrix (ECM) production and phenotype maintenance. Bovine primary chondrocytes were cultured on smooth PP and PS, as well as on nanostructured micropillar PP (patterned PP) and PS (patterned PS) for 2 weeks. Subsequently, the samples were collected for fluorescein diacetate-based cell viability tests, for immunocytochemical assays of types I and II collagen, actin and vinculin, for scanning electronic microscopic analysis of cell morphology and distribution, and for gene expression assays of Sox9, aggrecan, procollagen α{sub 1}(II), procollagen α{sub 1}(X), and procollagen α{sub 2}(I) using quantitative RT-PCR assays. After two weeks of culture, the bovine primary chondrocytes had attached on both patterned PP and PS, while practically no adhesion was observed on smooth PP. However, the best adhesion of the cells was on smooth PS. The cells, which attached on patterned PP and PS surfaces synthesized types I and II collagen. The chondrocytes' morphology was extended, and an abundant ECM network formed around the attached chondrocytes on both patterned PP and PS. Upon passaging, no significant differences on the chondrocyte-specific gene expression were observed, although the highest expression level of aggrecan was observed on the patterned PS in passage 1 chondrocytes, and the expression level of procollagen α{sub 1}(II) appeared to decrease in passaged chondrocytes. However, the expressions of procollagen α{sub 2}(I) were increased in all passaged cell cultures. In conclusion, the bovine primary chondrocytes could be grown on patterned PS and PP surfaces, and they produced extracellular matrix network around the adhered cells. However, neither the patterned PS nor PP could prevent the dedifferentiation of chondrocytes. - Highlights: • Methods to avoid chondrocyte dedifferentiation would be useful for cartilage

  18. Sequence and chromosomal localization of the mouse brevican gene

    DEFF Research Database (Denmark)

    Rauch, U; Meyer, H; Brakebusch, C

    1997-01-01

    Brevican is a brain-specific proteoglycan belonging to the aggrecan family. Phage clones containing the complete mouse brevican open reading frame of 2649 bp and the complete 3'-untranslated region of 341 bp were isolated from a mouse brain cDNA library, and cosmid clones containing the mouse...

  19. Clinical Trial and In Vitro Study for the Role of Cartilage and Synovia in Acute Articular Infection

    DEFF Research Database (Denmark)

    Langenmair, E. R.; Kubosch, E. J.; Salzmann, G. M.

    2015-01-01

    concentrations were also found in the in vitro model without chondrocytes (p chondrocytes. In contrast, FasL levels increased steadily in vitro......, reaching higher levels without chondrocytes (p chondrocytes. The cartilage-metabolismmarkers aggrecan and bFGF were at higher concentrations in intact joints, but also synthesized by SFB...

  20. Comparison of Leishmania typing results obtained from 16 European clinical laboratories in 2014.

    Science.gov (United States)

    Van der Auwera, Gert; Bart, Aldert; Chicharro, Carmen; Cortes, Sofia; Davidsson, Leigh; Di Muccio, Trentina; Dujardin, Jean-Claude; Felger, Ingrid; Paglia, Maria Grazia; Grimm, Felix; Harms, Gundel; Jaffe, Charles L; Manser, Monika; Ravel, Christophe; Robert-Gangneux, Florence; Roelfsema, Jeroen; Töz, Seray; Verweij, Jaco J; Chiodini, Peter L

    2016-12-08

    Leishmaniasis is endemic in southern Europe, and in other European countries cases are diagnosed in travellers who have visited affected areas both within the continent and beyond. Prompt and accurate diagnosis poses a challenge in clinical practice in Europe. Different methods exist for identification of the infecting Leishmania species. Sixteen clinical laboratories in 10 European countries, plus Israel and Turkey, conducted a study to assess their genotyping performance. DNA from 21 promastigote cultures of 13 species was analysed blindly by the routinely used typing method. Five different molecular targets were used, which were analysed with PCR-based methods. Different levels of identification were achieved, and either the Leishmania subgenus, species complex, or actual species were reported. The overall error rate of strains placed in the wrong complex or species was 8.5%. Various reasons for incorrect typing were identified. The study shows there is considerable room for improvement and standardisation of Leishmania typing. The use of well validated standard operating procedures is recommended, covering testing, interpretation, and reporting guidelines. Application of the internal transcribed spacer 1 of the rDNA array should be restricted to Old World samples, while the heat-shock protein 70 gene and the mini-exon can be applied globally. This article is copyright of The Authors, 2016.

  1. Hardy type inequalities with kernels: The current status and some new results

    Czech Academy of Sciences Publication Activity Database

    Kufner, Alois; Persson, L. E.; Samko, N.

    2017-01-01

    Roč. 290, č. 1 (2017), s. 57-65 ISSN 0025-584X Institutional support: RVO:67985840 Keywords : Hardy operators with kernels * Hardy type inequalities * new scales of characterizations Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.742, year: 2016 http://dx.doi.org/10.1002/mana.201500363

  2. Some Fixed Point Results for Caristi Type Mappings in Modular Metric Spaces with an Application

    Directory of Open Access Journals (Sweden)

    Duran Turkoglu

    2016-08-01

    Full Text Available In this paper we give Caristi type fixed point theorem in complete modular metric spaces. Moreover we give a theorem which can be derived from Caristi type. Also an application for the bounded solution of funcional equations is investigated.

  3. [THE COMPARATIVE ANALYSIS OF RESULTS OF DETECTION OF CARCINOGENIC TYPES OF HUMAN PAPILLOMA VIRUS BY QUALITATIVE AND QUANTITATIVE TESTS].

    Science.gov (United States)

    Kuzmenko, E T; Labigina, A V; Leshenko, O Ya; Rusanov, D N; Kuzmenko, V V; Fedko, L P; Pak, I P

    2015-05-01

    The analysis of results of screening (n = 3208; sexually active citizen aged from 18 to 59 years) was carried out to detect oncogene types of human papilloma virus in using qualitative (1150 females and 720 males) and quantitative (polymerase chain reaction in real-time (843 females and 115 males) techniques. The human papilloma virus of high oncogene type was detected in 65% and 68.4% of females and in 48.6% and 53% of males correspondingly. Among 12 types of human papilloma virus the most frequently diagnosed was human papilloma virus 16 independently of gender of examined and technique of analysis. In females, under application of qualitative tests rate of human papilloma virus 16 made up to 18.3% (n = 280) and under application of quantitative tests Rte of human papilloma virus made up to 14.9% (n = 126; p ≤ 0.05). Under examination of males using qualitative tests rate of human papilloma virus 16 made up to 8.3% (n = 60) and under application of qualitative tests made up to 12.2% (n = 14; p ≥ 0.05). Under application of qualitative tests rate of detection on the rest ofoncogene types of human papilloma virus varied in females from 3.4% to 8.4% and in males from 1.8% to 5.9%. Under application of qualitative tests to females rate of human papilloma virus with high viral load made up to 68.4%, with medium viral load - 2.85% (n = 24) and with low viral load -0.24% (n = 2). Under application of quantitative tests in males rate of detection of types of human papilloma virus made up to 53% and at that in all high viral load was established. In females, the most of oncogene types of human papilloma virus (except for 31, 39, 59) are detected significantly more often than in males.

  4. In vitro cell quality of articular chondrocytes assigned for autologous implantation in dependence of specific patient characteristics

    DEFF Research Database (Denmark)

    Pestka, Jan M; Schmal, Hagen; Salzmann, Gian

    2011-01-01

    OBJECTIVE: Autologous chondrocyte implantation (ACI) is a well-established therapeutic option for the treatment of cartilage defects of the knee joint. Since information concerning the cellular aspects of ACI is still limited, the aim of the present study was to investigate relevant differences...... between chondrocyte quality after in vitro cultivation and possible correlations with patient-specific factors. DESIGN: Cell quality of 252 consecutive ACI patients was assessed after chondrocyte in vitro expansion by determination of the expression of cartilage relevant surface marker CD44 and cartilage......, aggrecan or collagen type II nor cell density or viability after proliferation seemed to correlate with the grade of joint degeneration, defect aetiology or patient gender. However, chondrocytes harvested from the knee joints of patients at less than 20 years of age showed significantly higher expression...

  5. Klebsiella Typing

    DEFF Research Database (Denmark)

    Hansen, D S; Skov, R; Benedí, J.V.

    2002-01-01

    OBJECTIVE: To compare pulsed-field gel electrophoresis (PFGE) typing and O:K-serotyping of Klebsiella in two different epidemiological settings. METHODS: One hundred and four bacteremia isolates without known epidemiological relation and 47 isolates from an outbreak in a neonatal intensive care...... unit (NICU) were K-typed by countercurrent immunoelectrophoresis (CCIE), O-typed by an inhibition enzyme-linked immunosorbent assay method, and typed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme XbaI. RESULTS: Typing data for the 104 bacteremia isolates were compared...... with regard to typability, number of types, maximum number of isolates per type, and the Discriminative Index (DI). O-typing combined with K-typing (DI 0.98) as O:K-serotyping (DI 0.99) gave a very discriminative typing system, whereas O-typing alone was not very discriminative (DI 0.76). PFGE (DI 1...

  6. Homocysteine levels are associated with the results of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

    Energy Technology Data Exchange (ETDEWEB)

    Anan, Futoshi; Yonemochi, Hidetoshi; Nakagawa, Mikiko; Saikawa, Tetsunori [Oita University, Department of Cardiovascular Science, Faculty of Medicine, Hasama, Oita (Japan); Masaki, Takayuki; Takahashi, Naohiko; Yoshimatsu, Hironobu [Oita University, Department of Internal Medicine I, Oita (Japan); Eshima, Nobuoki [Oita University, Department of Biostatistics, School of Medicine, Oita (Japan)

    2007-01-15

    Elevated total plasma homocysteine (tHcy) levels and cardiovascular autonomic dysfunction are associated with a high mortality in type 2 diabetic patients. We tested the hypothesis that hyperhomocysteinemia is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The study group consisted of 17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58{+-}5 years, high tHcy group). The control group consisted of 23 age-matched type 2 diabetic patients with normal tHcy levels ({<=}15 mmol/l, age 58{+-}9 years, normal tHcy group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed {sup 123}I-MIBG myocardial uptake values were lower (p<0.005 and p<0.01, respectively) and the percent washout rate of {sup 123}I-MIBG was higher (p<0.001) in the high tHcy group than in the normal tHcy group. The fasting plasma insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index values (p<0.0001) were higher in the high tHcy group than in the normal tHcy group. Multiple regression analysis revealed that the level of tHcy was independently predicted by the HOMA index values and the myocardial uptake of {sup 123}I-MIBG at the delayed phase. Our results demonstrate that high levels of tHcy are associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. (orig.)

  7. Real-time PCR for type-specific identification of herpes simplex in clinical samples: evaluation of type-specific results in the context of CNS diseases.

    Science.gov (United States)

    Meylan, Sylvain; Robert, Daniel; Estrade, Christine; Grimbuehler, Valérie; Péter, Olivier; Meylan, Pascal R; Sahli, Roland

    2008-02-01

    HSV-1 and HSV-2 cause CNS infections of dissimilar clinico-pathological characteristics with prognostic and therapeutic implications. To validate a type-specific real-time PCR that uses MGB/LNA Taqman probes and to review the virologico-clinical data of 25 eligible patients with non-neonatal CNS infections. This real-time PCR was evaluated against conventional PCR (26 CSF and 20 quality controls), and LightCycler assay (51 mucocutaneous, 8 CSF and 32 quality controls) and culture/immunofluorescence (75 mucocutaneous) to assess typing with independent methods. Taqman real-time PCR detected 240 HSV genomes per ml CSF, a level appropriate for the management of patients, and provided unambiguous typing for the 104 positive (62 HSV-1 and 42 HSV-2) out the 160 independent clinical samples tested. HSV type diagnosed by Taqman real-time PCR predicted final diagnosis (meningitis versus encephalitis/meningoencephalitis, p<0.001) in 24/25 patients at time of presentation, in contrast to clinical evaluation. Our real-time PCR, as a sensitive and specific means for type-specific HSV diagnosis, provided rapid prognostic information for patient management.

  8. Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

    Science.gov (United States)

    Yin, Yuxin; Lan, James H; Nguyen, David; Valenzuela, Nicole; Takemura, Ping; Bolon, Yung-Tsi; Springer, Brianna; Saito, Katsuyuki; Zheng, Ying; Hague, Tim; Pasztor, Agnes; Horvath, Gyorgy; Rigo, Krisztina; Reed, Elaine F; Zhang, Qiuheng

    2016-01-01

    Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT), HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS) of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP) registry donors using long-range PCR by next generation sequencing (NGS) approach on buccal swab DNA. Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C) from promotor to 3' UTR. Class II genes (DRB1, DQB1) were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML) format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing. Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%), 92 rare alleles (0.091%) and 42 exon novelties (0.042%). Long

  9. Application of High-Throughput Next-Generation Sequencing for HLA Typing on Buccal Extracted DNA: Results from over 10,000 Donor Recruitment Samples.

    Directory of Open Access Journals (Sweden)

    Yuxin Yin

    Full Text Available Unambiguous HLA typing is important in hematopoietic stem cell transplantation (HSCT, HLA disease association studies, and solid organ transplantation. However, current molecular typing methods only interrogate the antigen recognition site (ARS of HLA genes, resulting in many cis-trans ambiguities that require additional typing methods to resolve. Here we report high-resolution HLA typing of 10,063 National Marrow Donor Program (NMDP registry donors using long-range PCR by next generation sequencing (NGS approach on buccal swab DNA.Multiplex long-range PCR primers amplified the full-length of HLA class I genes (A, B, C from promotor to 3' UTR. Class II genes (DRB1, DQB1 were amplified from exon 2 through part of exon 4. PCR amplicons were pooled and sheared using Covaris fragmentation. Library preparation was performed using the Illumina TruSeq Nano kit on the Beckman FX automated platform. Each sample was tagged with a unique barcode, followed by 2×250 bp paired-end sequencing on the Illumina MiSeq. HLA typing was assigned using Omixon Twin software that combines two independent computational algorithms to ensure high confidence in allele calling. Consensus sequence and typing results were reported in Histoimmunogenetics Markup Language (HML format. All homozygous alleles were confirmed by Luminex SSO typing and exon novelties were confirmed by Sanger sequencing.Using this automated workflow, over 10,063 NMDP registry donors were successfully typed under high-resolution by NGS. Despite known challenges of nucleic acid degradation and low DNA concentration commonly associated with buccal-based specimens, 97.8% of samples were successfully amplified using long-range PCR. Among these, 98.2% were successfully reported by NGS, with an accuracy rate of 99.84% in an independent blind Quality Control audit performed by the NDMP. In this study, NGS-HLA typing identified 23 null alleles (0.023%, 92 rare alleles (0.091% and 42 exon novelties (0.042%.Long

  10. Type classes for mathematics in type theory

    OpenAIRE

    Spitters, Bas; Van der Weegen, Eelis

    2011-01-01

    The introduction of first-class type classes in the Coq system calls for re-examination of the basic interfaces used for mathematical formalization in type theory. We present a new set of type classes for mathematics and take full advantage of their unique features to make practical a particularly flexible approach formerly thought infeasible. Thus, we address both traditional proof engineering challenges as well as new ones resulting from our ambition to build upon this development a library...

  11. Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells.

    Science.gov (United States)

    Lin, Hui; Ma, Xuan; Wang, Bai-Chuan; Zhao, Lei; Liu, Jian-Xiang; Pu, Fei-Fei; Hu, Yi-Qiang; Hu, Hong-Zhi; Shao, Zeng-Wu

    2017-11-15

    Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca 2+ ] i ) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca 2+ ] i . In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The effect of desulfation of chondroitin sulfate on interactions with positively charged growth factors and upregulation of cartilaginous markers in encapsulated MSCs.

    Science.gov (United States)

    Lim, Jeremy J; Temenoff, Johnna S

    2013-07-01

    Sulfated glycosaminoglycans (GAGs) are known to interact electrostatically with positively charged growth factors to modulate signaling. Therefore, regulating the degree of sulfation of GAGs may be a promising approach to tailor biomaterial carriers for controlled growth factor delivery and release. For this study, chondroitin sulfate (CS) was first desulfated to form chondroitin, and resulting crosslinked CS and chondroitin hydrogels were examined in vitro for release of positively charged model protein (histone) and for their effect on cartilaginous differentiation of encapsulated human mesenchymal stem cells (MSCs). Desulfation significantly increased the release of histone from chondroitin hydrogels (30.6 ± 2.3 μg released over 8 days, compared to natively sulfated CS with 20.2 ± 0.8 μg), suggesting that sulfation alone plays a significant role in modulating protein interactions with GAG hydrogels. MSCs in chondroitin hydrogels significantly upregulated gene expression of collagen II and aggrecan by day 21 in chondrogenic medium (115 ± 100 and 23.1 ± 7.9 fold upregulation of collagen II and aggrecan, respectively), compared to CS hydrogels and PEG-based swelling controls, indicating that desulfation may actually enhance the response of MSCs to soluble chondrogenic cues, such as TGF-β1. Thus, desulfated chondroitin materials present a promising biomaterial tool to further investigate electrostatic GAG/growth factor interactions, especially for repair of cartilaginous tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Cierny-Mader Type III chronic osteomyelitis: the results of patients treated with debridement, irrigation, vancomycin beads and systemic antibiotics

    Science.gov (United States)

    Karaduman, Mert

    2007-01-01

    Cierny-Mader (C-M) Type III osteomyelitis is defined as a localised lesion with both medullary and cortical involvement that is stable mechanically after debridement. The treatment of C-M Type III osteomyelitisis is difficult and requires a precise protocol to achieve a disease-free long-term follow-up. We report here the results of our study on 26 patients (19 men and 7 women; average age: 34.7 years) with C-M Type III osteomylelitis who were treated with radical debridement, irrigation, vancomycin-impregnated custom-made beads and culture-specific systemic antibiotics. Those patients with metaphyseal involvement were treated with deroofing of the cortex and debridement by means of a “trough” (16 patients); those with diaphyseal involvement were treated with both intramedullary reaming and debridement from a trough (ten patients). Antibiotic cement rods were used as an additional therapy in five patients with diaphyseal involvement. Recurrence developed in three patients and was attributed to inadequate debridement; all three patients were treated again in the same manner with success. The mean follow-up is currently 3.6 years (range: 2–6 years). All of the patients have normal clinical, radiographic and laboratory parameters, and all are ambulatory and have returned to their pretreatment level of activity or better. We conclude that C-M Type III chronic osteomyelitis can be safely treated with this protocol. PMID:17375299

  14. Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling

    Science.gov (United States)

    Potempa, Krzysztof; Graham, Christine M.; Moreira-Teixeira, Lucia; McNab, Finlay W.; Howes, Ashleigh; Stavropoulos, Evangelos; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; O’Garra, Anne

    2016-01-01

    Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response. Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection. Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFNαβ receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes. Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection. A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2. Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice. These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes. PMID:26918359

  15. Host-Parasite Interactions in Individuals with Type 1 and 2 Diabetes Result in Higher Frequency of Ascaris lumbricoides and Giardia lamblia in Type 2 Diabetic Individuals

    Directory of Open Access Journals (Sweden)

    Eleuza Rodrigues Machado

    2018-01-01

    Full Text Available Host-parasite interactions in diabetic patients might influence diabetes complications and intestinal parasitosis. The aim was to investigate the occurrence of enteroparasites in individuals with diabetes types 1 and 2. A descriptive study was designed to estimate frequencies of parasites and to compare them in individuals with diabetes types 1 and 2 from two Health Centers and one hospital in the Federal District of Brazil. Patients were allocated to the study by convenience. Three fecal samples of 156 diabetic individuals (120 type 1 and 36 type 2 were analyzed using two parasitological methods. Enteroparasites or commensals frequency in diabetics was 64%. Diabetics infected with up to six species of intestinal parasites or commensals were found. Frequencies of Ascaris lumbricoides and Giardia lamblia were higher in individuals with type 2 diabetes. The lower frequency of A. lumbricoides found in type 1 diabetes may be related to a strong Th2 response to parasites. Autoimmune response developed in type 1 diabetic individuals characterized by the production of Th1 cytokines could explain low frequency of G. lamblia. High frequency of parasites found in type 2 diabetes emphasizes the importance of periodic parasitological examinations in these individuals.

  16. Several types of types in programming languages

    OpenAIRE

    Martini, Simone

    2015-01-01

    Part 2: Regular Submissions; International audience; Types are an important part of any modern programming language, but we often forget that the concept of type we understand nowadays is not the same it was perceived in the sixties. Moreover, we conflate the concept of " type " in programming languages with the concept of the same name in mathematical logic, an identification that is only the result of the convergence of two different paths, which started apart with different aims. The paper...

  17. Study on natural convection in core barrel. Experimental and numerical results for band type spacer pads

    International Nuclear Information System (INIS)

    Hayashi, Kenji; Kawamata, Nobuhiro; Kamide, Hideki

    2003-03-01

    In a fast reactor an Inter-Wrapper Flow (IWF) is one of significant phenomena for decay heat removal under natural circulation condition, when a direct reactor auxiliary cooling system (DRACS) is adopted for decay heat removal system. Cold coolant provided by dipped heat exchangers (DHX) of DRACS can penetrate into the core barrel (region between the subassemblies) and it makes natural convection int he core barrel. Such IWF will depend on a spacer pad geometry of subassemblies. Water experiment, TRIF (Test Rig for Inter-wrapper Flow), was carried out for IWF in a reactor core. The test section modeled a 1/12th sector of the core and upper plenum of reactor vessel. Experimental parameters were the spacer pad geometry and flow path geometries connecting the upper plenum and core barrel. Numerical simulation using AQUA code was also performed to confirm applicability of a simulation method. An experimental series using a button type spacer pad had been carried out. Here a band type spacer pad was examined. Temperatures at subassembly wall were measured with parameter of the flow path geometries; one was a connection pipe between the upper plenum and core barrel and the other was flow hole in core former plates between the outermost subassemblies and the core barrel. It was found that these flow paths were effective to remove heat in the core in case of the band type spacer pad. A general purpose three dimensional analysis code, AQUA, was applied to the experimental analysis. Each subassembly and inter wrapper gap region were modeled by slab mesh geometry. Pressure loss coefficient at the pacer pad was set based on the geometry. The numerical simulation results were in good agreement with measured temperature profiles in the core. (author)

  18. Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.

    OpenAIRE

    Smith, L T; Wertelecki, W; Milstone, L M; Petty, E M; Seashore, M R; Braverman, I M; Jenkins, T G; Byers, P H

    1992-01-01

    Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently ide...

  19. Condom use with different types of sexual partners in Ukraine: results of 2007 survey

    Directory of Open Access Journals (Sweden)

    Barska, Julia

    2012-07-01

    Full Text Available BACKGROUND: Use of condoms is recommended in all risky sexual contacts, as long as a couple becomes monogamous and tests for HIV and other STDs. This research aims to examine whether people in Ukraine follow this recommendation.MATERIAL AND METHODS: Associations between condom use at last sexual intercourse and type of sexual partner were explored separately for men and women based on data of 2007 survey by using regression models adjusted for knowledge about and attitude to STDs and HIV, contraception and pregnancy, risky behaviour and socio-demographic characteristics.RESULTS: Generally, 37.2% of men and 25.2% of women reported using condom at last sexual contact. Overall, use of condoms increased with less intimacy between partners: 22.6% of men and 19.2% of women used condoms with their spouses, 62.8% and 52.4% ― with girl-/boy-friends, somewhat less – 56.6% and 35.3% ― with casual acquaintance, respectively, and 71.4% of men – with commercial sex workers; in multivariate analysis direction of associations remained the same. Moreover, risky sexual behaviour for both genders, and drugs ever-use and alcohol consumption during last sex for men reduces odds of using condoms. Also, men demonstrating correct knowledge of ways of horizontal transmission of HIV and women aware about ways of prevention of HIV transmission had higher odds of using condoms, as well as women confident in their ability to buy condoms. For socio-demographic characteristics, having children, younger age and dwelling in non-Western regions and cities were positively associated with using condoms.DISCUSSION AND CONCLUSIONS: Although condom use in Ukraine is not prevalent enough, there is a tendency to more frequent use of them with high-risk sexual partners. At the same time, people practicing other types of risky behaviour use condoms less, too.

  20. Associations of Circulating Lymphocyte Subpopulations with Type 2 Diabetes: Cross-Sectional Results from the Multi-Ethnic Study of Atherosclerosis (MESA.

    Directory of Open Access Journals (Sweden)

    Nels C Olson

    Full Text Available Distinct lymphocyte subpopulations have been implicated in the regulation of glucose homeostasis and obesity-associated inflammation in mouse models of insulin resistance. Information on the relationships of lymphocyte subpopulations with type 2 diabetes remain limited in human population-based cohort studies.Circulating levels of innate (γδ T, natural killer (NK and adaptive immune (CD4+ naive, CD4+ memory, Th1, and Th2 lymphocyte subpopulations were measured by flow cytometry in the peripheral blood of 929 free-living participants of the Multi-Ethnic Study of Atherosclerosis (MESA. Cross-sectional relationships of lymphocyte subpopulations with type 2 diabetes (n = 154 and fasting glucose and insulin concentrations were evaluated by generalized linear models.Each standard deviation (SD higher CD4+ memory cells was associated with a 21% higher odds of type 2 diabetes (95% CI: 1-47% and each SD higher naive cells was associated with a 22% lower odds (95% CI: 4-36% (adjusted for age, gender, race/ethnicity, and BMI. Among participants not using diabetes medication, higher memory and lower naive CD4+ cells were associated with higher fasting glucose concentrations (p<0.05, adjusted for age, sex, and race/ethnicity. There were no associations of γδ T, NK, Th1, or Th2 cells with type 2 diabetes, glucose, or insulin.A higher degree of chronic adaptive immune activation, reflected by higher memory and lower naive CD4+ cells, was positively associated with type 2 diabetes. These results are consistent with a role of chronic immune activation and exhaustion augmenting chronic inflammatory diseases, and support the importance of prospective studies evaluating adaptive immune activation and type 2 diabetes.

  1. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib : Results of the European Study on Glycogen Storage Disease Type I

    NARCIS (Netherlands)

    Visser, G; Rake, JP; Fernandes, J; Labrune, P; Leonard, JV; Moses, S; Ullrich, K; Smit, GPA

    Objective: To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib. Method: As part of a collaborative European Study on GSD type I, a retrospective registry was established in

  2. The signs of differentiation of chondrocytes in the formation of early cartilage lesions in the elderly

    Directory of Open Access Journals (Sweden)

    Elena Vasil'evna Chetina

    2011-01-01

    Results. The activity of collagen type II cleavage was shown to be increased in the area of age-related OA-like cartilage lesions. This was accompanied by the high expression of collagenases of metalloproteinases (MMP 1, 14 (MT1-MMP, aggrecanases - desintegrin and MMP with thrombospondin type 1 motif (ADAMTS 5, the cytokines of interleukins (IL 1α/β and tumor necrosis factor-α (TNF-α, as well as the genes associated with chondrocyte hypertrophy of type X collagen (C0L10A1, MMP 13 and 9, Indian hedgehog (Ihh and cas-pase 3 in the immediate vicinity of a lesion area. At the same time, there was a high expression of growth factors associated with the proliferation phase of chondrocytes, namely: parathyroid hormone-related peptide (PTHrP, fibroblast growth factor-2 (FGF-2, transforming growth factor β1/2 (TGF-β1/2, as well as macromolecules of matrix of type II collagen (C0L2A1 and aggrecan in both the areas adjacent to the lesions and at a considerable distance from their center. However, these areas showed no higher collagen cleavage activity. Nether higher collagen cleavage, nor excess expression of the genes examined were observed in the absolutely intact cartilage areas. Conclusion. Our studies have indicated that the area of very early age-related OA-like focal cartilage lesions exhibits enhanced type II collagen cleavage that is attended by the expression of the genes associated with chondrocyte differentiation in the embryonic growth plate.

  3. Types and Automata

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Meineche Smidt, Erik

    A hierarchical type system for imperative programming languages gives rise to various computational problems, such as type equivalence, type ordering, etc. We present a particular class of finite automata which are shown to be isomorphic to type equations. All the relevant type concepts turn out...... to have well-known automata analogues, such as language equality, language inclusion, etc. This provides optimal or best known algorithms for the type system, by a process of translating type equations to automata, solving the analogous problem, and translating the result back to type equations. Apart...

  4. Study of Carbon Nano-Tubes Effects on the Chondrogenesis of Human Adipose Derived Stem Cells in Alginate Scaffold

    Directory of Open Access Journals (Sweden)

    Ali Valiani

    2014-01-01

    Full Text Available Background: Osteoarthritis is one of the most common diseases in middle-aged populations in the World and could become the fourth principal cause of disability by the year 2020. One of the critical properties for cartilage tissue engineering (TE is the ability of scaffolds to closely mimic the extracellular matrix and bond to the host tissue. Therefore, TE has been presented as a technique to introduce the best combination of cells and biomaterial scaffold and to stimulate growth factors to produce a cartilage tissue resembling natural articular cartilage. The aim of study is to improve differentiation of adipose derived stem cells (ADSCs into chondrocytes in order to provide a safe and modern treatment for patients suffering from cartilage damages. Methods: After functionalization, dispersions and sterilizing carbon nano-tubes (CNTs, a new type of nanocomposite gel was prepared from water-soluble CNTs and alginate. ADSCs seeded in 1.5% alginate scaffold and cultured in chondrogenic media with and without transforming growth factor-β1 (TGF-β1 for 7 and 14 days. The genes expression of sex determining region Y-box 9 (SOX9, types II and X collagens was assessed by real-time polymerase chain reaction and the amount of aggrecan (AGC and type I collagen was measured by ELISA. Results: Our findings showed that the expression of essential cartilage markers, SOX9, type II collagen and AGC, in differentiated ADSCs at the concentration of 1 μg/ml CNTs in the presence of TGF-β1 were significantly increased in comparison with the control group (P < 0.001. Meanwhile, type X collagen expression and also type I collagen production were significantly decreased (P < 0.001. Conclusions: The results showed that utilized three-dimensional scaffold had a brilliant effect in promoting gene expression of chondrogenesis.

  5. Hypoglycaemia in patients with type 1 and type 2 diabetes mellitus on insulin therapy. Results of the global HAT study in Argentina

    Directory of Open Access Journals (Sweden)

    José E. Costa Gil

    2017-12-01

    Full Text Available We describe the results of the HAT study in 433 Argentinean patients with type 1 diabetes (T1D and 823 with type 2 diabetes (T2D. HAT was an international non-interventional study assessing severe and non-severe hypoglycaemia in patients with T1D and T2D under insulin treatment through a two-part self-assessment questionnaire (retrospective and prospective. The annual incidence of at least one hypoglycaemic episode was 46 episode/patient/year in T1D and 14.2 in T2D (retrospective, 96.5 and 24.6 episode/patient/year in T1D and T2D, respectively (prospective. Hypoglycaemia affected quality of life (on a scale of 0-10 for fear of hypoglycaemia: 60% in T1D and 37.6% in T2D scored 5 to 10, daily life, occupational or academic performance (2.1% with T1D and 3.2% with T2D did not attend to their work after hypoglycaemia, and induced an increased use of health resources (T1D: 66.1% increased glucose monitoring, 60.5% food intake, 51% consultations, 3.5% hospital admissions; 60.5% reduced insulin and 20.9% exercises; T2D increased 46.2% glucose monitoring, 43.8% consultations, 38.6% food intake, 24.1% reduced and 13.9% skipped the insulin dose and 14.3% suspended exercises. Greater numbers of episodes were recorded in the prospective period. An instrument to assess hypoglycaemia in clinical practice and strategies to reduce their risk are required. It is also important to ask about the episodes and reinforce the education of patients and close relatives on hypoglycaemia prevention and treatment

  6. Gender disparities in diabetes and coronary heart disease medication among patients with type 2 diabetes: results from the DIANA study

    Directory of Open Access Journals (Sweden)

    Krämer Heike U

    2012-07-01

    Full Text Available Abstract Background Coronary heart disease (CHD is one of the most common long-term complications in people with type 2 diabetes. We analyzed whether or not gender differences exist in diabetes and CHD medication among people with type 2 diabetes. Methods The study was based on data from the baseline examination of the DIANA study, a prospective cohort study of 1,146 patients with type 2 diabetes conducted in South-West Germany. Information on diabetes and CHD medication was obtained from the physician questionnaires. Bivariate and multivariate analyses using logistic regression were employed in order to assess associations between gender and prescribed drug classes. Results In total, 624 men and 522 women with type 2 diabetes with a mean age of 67.2 and 69.7 years, respectively, were included in this analysis. Compared to women, men had more angiopathic risk factors, including smoking, alcohol consumption and worse glycemic control, and had more often a diagnosed CHD. Bivariate analyses showed higher prescription of thiazolidinediones and oral combination drugs as well as of angiotensin-converting enzyme (ACE inhibitors, calcium channel blockers and aspirin in men than in women. After full adjustment, differences between men and women remained significant only for ACE inhibitors (OR = 1.44; 95%-confidence interval (CI: 1.11 – 1.88 and calcium channel blockers (OR = 1.42, 95%-CI: 1.05 – 1.91. Conclusions These findings contribute to current discussions on gender differences in diabetes care. Men with diabetes are significantly more likely to receive oral combination drugs, ACE inhibitors and calcium channel blockers in the presence of coronary heart disease, respectively. Our results suggest, that diabetic men might be more thoroughly treated compared to women. Further research is needed to focus on reasons for these differences mainly in treatment of cardiovascular diseases to improve quality of care.

  7. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Damm, Peter; Jovanovic, Lois

    2011-01-01

    hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c ≤ 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks...... with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal...... of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine...

  8. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Damm, Peter; Jovanovic, Lois

    2011-01-01

    hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c = 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks...... with prandial insulin aspart. The results are expected mid-2011 with full publications expected later this year. Baseline characteristics show that basal insulin analogues are already frequently used in pregnant women with type 1 diabetes. This study will hopefully elucidate the safety and efficacy of the basal...... of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine...

  9. Uncontrolled non-heartbeating donors (types i-ii) with normothermic recirculation vs. heartbeating donors: evaluation of functional results and survival.

    Science.gov (United States)

    Miranda-Utrera, N; Medina-Polo, J; Pamplona-Casamayor, M; Passas-Martínez, J B; Rodríguez-Antolín, A; de la Rosa Kehrmann, F; Duarte-Ojeda, J M; Tejido-Sánchez, A; Villacampa Aubá, F; Andrés Belmonte, A

    2015-09-01

    Non-heartbeating donors (NHBD) are an alternative to heartbeating donors (HBD). Our objective was to compare functional results and kidney survival from NHBDs and HBDs. A retrospective study comparing the results of 236 normothermically preserved kidneys from type i and ii type NHBDs with the results of 250 from HBDs that were transplanted in our center between 2005 and 2012. Homogeneity between groups was tested and we evaluated the presence of delayed graft function (DGF) associated with pretransplant variables of the donor and recipient. Both groups show homogeneity in pretransplant characteristics in terms of: age, HLA incompatibilities, and recipient hemodialysis time. Average follow-up time was 33 months (range 0-87) for NHBDs and 38 months (range 0-90) for HBDs. 5.5% of NHBDs showed primary non-function (PNF) vs. 4% of HBDs (P=.42) and 80.9% of DGF vs. 46.8% of HBDs (P<.001). At the end of the follow-up, there were no statistically significant differences in the survival of grafts (92.8% for NHBD vs. 93.6% for HBD, P=.71) and recipients (99.1% NHBD vs. 98.6% HBD, P=.28). Although the DGF percentage was greater for NHBDs, final creatinine as well as graft and recipient survival were similar for both groups. Therefore, in our experience, kidneys from NHBDs have similar results to those from HBDs and are an excellent source of organs for transplantation. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Raviart–Thomas-type sources adapted to applied EEG and MEG: implementation and results

    International Nuclear Information System (INIS)

    Pursiainen, S

    2012-01-01

    This paper studies numerically electroencephalography and magnetoencephalography (EEG and MEG), two non-invasive imaging modalities in which external measurements of the electric potential and the magnetic field are, respectively, utilized to reconstruct the primary current density (neuronal activity) of the human brain. The focus is on adapting a Raviart–Thomas-type source model to meet the needs of EEG and MEG applications. The goal is to construct a model that provides an accurate approximation of dipole source currents and can be flexibly applied to different reconstruction strategies as well as to realistic computation geometries. The finite element method is applied in the simulation of the data. Least-squares fit interpolation is used to establish Cartesian source directions, which guarantee that the recovered current field is minimally dependent on the underlying finite element mesh. Implementation is explained in detail and made accessible, e.g., by using quadrature-free formulae and the Gaussian one-point rule in numerical integration. Numerical results are presented concerning, for example, the iterative alternating sequential inverse algorithm as well as resolution, smoothness and local refinement of the finite element mesh. Both spherical and pseudo-realistic head models, as well as real MEG data, are utilized in the numerical experiments. (paper)

  11. Depressive symptoms in youth with type 1 or type 2 diabetes: Results of the Pediatric Diabetes Consortium screening assessment of depression in diabetes study

    Science.gov (United States)

    To evaluate the frequency of depressive symptoms and the diagnosis and management of depression in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium T1D and T2D registries. The Children's Depression Inventory (CDI) 2 Self-Report (Short) version ...

  12. Spine deformities in patients with Ehlers-Danlos syndrome, type IV - late results of surgical treatment

    Directory of Open Access Journals (Sweden)

    Tesiorowski Maciej

    2010-11-01

    Full Text Available Abstract Background Spinal deformities in Ehlers-Danlos syndrome are usually progressive and may require operative treatment. There is limited number of studies describing late results of surgery in this disease. Methods This is a retrospective study of the records of 11 patients with Ehlers-Danlos syndrome type IV, treated surgically between 1990 and 2007. All patients underwent surgical treatment for spinal deformity. Duration of operation, type of instrumentation, intraoperative blood loss, complications and number of additional surgeries were noted. Radiographic measurement was performed on standing AP and lateral radiographs acquired before surgery, just after and at final follow up. Results The mean follow up period was 5.5 ± 2.9 years (range 1-10 years. The mean preoperative thoracic and lumbar curve were 109.5 ± 19.9° (range 83° - 142° and 75.6 ± 26.7° (range 40° - 108° respectively. Posterior spine fusion alone was performed on 6 patients and combined anterior and posterior fusion (one- or two stage on 5 cases. Posterior segmental spinal instrumentation was applied with use of hooks, screws and wires. The mean postoperative thoracic and lumbar curve improved to 79.3 ± 16.1° (range 56° - 105° and 58.5 ± 27.7° (range 10° - 95° respectively, with a slight loss of correction during follow up. The average thoracic and lumbar correction was 26.4 ± 14.9% (range 5.3 - 50.4% and 26.3 ± 21.2% (range 7.9 - 75%. Postoperatively, the mean kyphosis was 79.5 ± 40.3° (range 21° -170°, and lordosis was 50.8 ± 18.6° (range 20° -79°. Hyperkyphosis increased during follow up while lordosis remained stable. Mean Th12-L2 angle was -3.5 ±9.9° (range -19° - 15° postoperatively and did not change significantly during follow up. Conclusions Huge spinal deformities in patients with Ehlers-Danlos syndrome require complex and extensive surgery. There is a big risk of sagittal imbalance in this group.

  13. Commissioning and first results of scanning type EXAFS beamline (BL-09) at INDUS-2 synchrotron source

    Energy Technology Data Exchange (ETDEWEB)

    Poswal, A. K., E-mail: poswalashwini@gmail.com; Agrawal, A., E-mail: poswalashwini@gmail.com; Yadav, A. K., E-mail: poswalashwini@gmail.com; Nayak, C., E-mail: poswalashwini@gmail.com; Basu, S., E-mail: poswalashwini@gmail.com; Bhattachryya, D.; Jha, S. N.; Sahoo, N. K. [Atomic and Molecular Physics Division, Bhabha Atomic Research Centre, Mumbai -400085 (India); Kane, S. R.; Garg, C. K. [Indus Synchrotrons Utilization Division, Raja Ramanna Centre for Advanced Technology, Indore- 452013 (India)

    2014-04-24

    An Energy Scanning X-ray Absorption Fine Structure spectroscopy beamline has recently been installed and commissioned at BL-09 bending magnet port of INDUS-2 synchrotron source, Indore. The beamline uses an UHV compatible fixed exit double crystal monochromator (DCM) with two Si (111) crystals. Two grazing incidence cylindrical mirrors are also used in this beamline; the pre-mirror is used as a collimating mirror while the post mirror is used for vertical focusing and higher harmonic rejection. In this beamline it is possible to carry out EXAFS measurements both in transmission and fluorescence mode on various types of samples, using Ionization chamber detectors and solid state drift detector respectively. In this paper, results from first experiments of the Energy Scanning EXAFS beamline are presented.

  14. Listeria monocytogenes Circulating in Rabbit Meat Products and Slaughterhouses in Italy: Prevalence Data and Comparison Among Typing Results.

    Science.gov (United States)

    De Cesare, Alessandra; Parisi, Antonio; Mioni, Renzo; Comin, Damiano; Lucchi, Alex; Manfreda, Gerardo

    2017-03-01

    Rabbit meat has outstanding dietetic and nutritional properties. However, few data on microbiological hazards associated with rabbit productions are available. In this study, the presence of Listeria monocytogenes was determined in 430 rabbit carcasses, 256 rabbit meat cuts and products, and 599 environmental sponges collected from four Italian rabbit slaughterhouses over a period of 1 year. Prevalence of L. monocytogenes among the 1285 rabbit meat and environmental samples was 11%, with statistically significant differences between slaughterhouses. The highest prevalence (33.6%) was observed in rabbit meat cuts and products; the majority of positive environmental samples were collected from conveyor belts. Overall, 27.9% and 14.3% of rabbit cuts and carcasses, respectively, had L. monocytogenes counts higher than 1 colony-forming unit (CFU)/10 g. A selection of 123 isolates from positive samples was genotyped and serotyped to determine genetic profiles and diversity among L. monocytogenes isolates contaminating different slaughterhouses and classes of products investigated. Discriminatory power and concordance among the results obtained using multilocus variable-number tandem-repeat analysis (MLVA), multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), automated EcoRI ribotyping, and serotyping were assessed. The isolates selected for typing were classified into serotypes 1/2a (52.8%), 1/2c (32.5%), and 1/2b (14.6%). The majority of the isolates were classified as ST14 (34.1%), ST9 (35.5%), ST121 (17.9%), and ST224 (14.6%). The greatest discriminatory power was observed with the MLVA typing, followed by MLST, PFGE, and ribotyping. The best bidirectional concordance was achieved between PFGE and MLST. There was 100% correlation between both MLST and MLVA with serotype. Moreover, a high unidirectional correspondence was observed between MLVA and both MLST and PFGE, as well as between PFGE and both MLST and serotyping. The results of this

  15. Sprifermin (rhFGF18) modulates extracellular matrix turnover in cartilage explants ex vivo

    DEFF Research Database (Denmark)

    Reker, Ditte; Kjelgaard-Petersen, Cecilie Freja; Siebuhr, Anne Sofie

    2017-01-01

    (ECM) production. To gain further insight into the process of sprifermin in the cartilage tissue, this study aimed at investigating the ECM turnover of articular cartilage explants in a longitudinal manner. Methods: Bovine full-depth articular cartilage explants were stimulated with sprifermin...... by immuno-histochemical detection of proliferating cell nuclear antigen. ECM turnover was quantified by biomarker ELISAs; ProC2 reflecting type II collagen formation, CS846 reflecting aggrecan formation, active MMP9, C2M and AGNx2 reflecting matrix metalloproteinase activity, and AGNx1 reflecting......, active MMP9 was slightly decreased, and AGNx1 was slightly increased. Over the course of treatment, the temporal order of ECM turnover responses was AGNx1, then ProC2, followed by CS846 and MMP9. Pro-inflammatory activation of the explants diminished the ECM turnover responses otherwise observed under...

  16. Hydroxyapatite and Calcified Elastin Induce Osteoblast-like Differentiation in Rat Aortic Smooth Muscle Cells

    Science.gov (United States)

    Lei, Yang; Sinha, Aditi; Nosoudi, Nasim; Grover, Ankit; Vyavahare, Naren

    2014-01-01

    Vascular calcification can be categorized into two different types. Intimal calcification related to atherosclerosis and elastin-specific medial arterial calcification (MAC). Osteoblast-like differentiation of vascular smooth muscle cells (VSMCs) has been shown in both types; however, how this relates to initiation of vascular calcification is unclear. We hypothesize that the initial deposition of hydroxyapatite-like mineral in MAC occurs on degraded elastin first and that causes osteogenic transformation of VSMCs. To test this, rat aortic smooth muscle cells (RASMCs) were cultured on hydroxyapatite crystals and calcified aortic elastin. Using RT-PCR and specific protein assays, we demonstrate that RASMCs lose their smooth muscle lineage markers like alpha smooth muscle actin (SMA) and myosin heavy chain (MHC) and undergo chondrogenic/osteogenic transformation. This is indicated by an increase in the expression of typical chondrogenic proteins such as aggrecan, collagen type II alpha 1(Col2a1) and bone proteins such as runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, when calcified conditions are removed, cells return to their original phenotype. Our data supports the hypothesis that elastin degradation and calcification precedes VSMCs' osteoblast-like differentiation. PMID:24447384

  17. Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed chitosan scaffold.

    Science.gov (United States)

    Ye, Ken; Felimban, Raed; Traianedes, Kathy; Moulton, Simon E; Wallace, Gordon G; Chung, Johnson; Quigley, Anita; Choong, Peter F M; Myers, Damian E

    2014-01-01

    Infrapatellar fat pad adipose stem cells (IPFP-ASCs) have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGFβ3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft.

  18. Chondrogenesis of infrapatellar fat pad derived adipose stem cells in 3D printed chitosan scaffold.

    Directory of Open Access Journals (Sweden)

    Ken Ye

    Full Text Available Infrapatellar fat pad adipose stem cells (IPFP-ASCs have been shown to harbor chondrogenic potential. When combined with 3D polymeric structures, the stem cells provide a source of stem cells to engineer 3D tissues for cartilage repair. In this study, we have shown human IPFP-ASCs seeded onto 3D printed chitosan scaffolds can undergo chondrogenesis using TGFβ3 and BMP6. By week 4, a pearlescent, cartilage-like matrix had formed that penetrated the top layers of the chitosan scaffold forming a 'cap' on the scaffold. Chondrocytic morphology showed typical cells encased in extracellular matrix which stained positively with toluidine blue. Immunohistochemistry demonstrated positive staining for collagen type II and cartilage proteoglycans, as well as collagen type I. Real time PCR analysis showed up-regulation of collagen type II, aggrecan and SOX9 genes when IPFP-ASCs were stimulated by TGFβ3 and BMP6. Thus, IPFP-ASCs can successfully undergo chondrogenesis using TGFβ3 and BMP6 and the cartilage-like tissue that forms on the surface of 3D-printed chitosan scaffold may prove useful as an osteochondral graft.

  19. Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko

    2015-12-23

    Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

  20. Bone morphogenetic protein-7 promotes chondrogenesis in human amniotic epithelial cells.

    Science.gov (United States)

    Zhou, Junjie; Yu, Guangrong; Cao, Chengfu; Pang, Jinhui; Chen, Xianqi

    2011-06-01

    Bone morphogenetic proteins (BMPs) play important roles at multiple stages of chondrogenesis. This study was undertaken to investigate the potential role of bone morphogenetic protein-7 (BMP-7) in the differentiation of chondrocytes using tissue engineering techniques. The impact of BMP-7 on human amniotic epithelial cells (hAECs) was tested. The hAECs were treated either with recombinant human BMP-7 cDNA or with transforming growth factor beta 1 (TGF-β1) as a positive control for three weeks in vitro. Cartilaginous differentiation and proliferation were assayed by quantitative RT-PCR, histology, and in situ hybridization. Our results were such that hAECs treated with either BMP-7 or TGF-β1 expressed cartilage markers (aggrecan, Sox9, CEP-68, and type II and X collagens) within three weeks. Compared with a control vector, BMP-7 induced a decrease in type I collagen expression, while the transcription of the cartilage-specific type II collagen remained stable. In induction experiments, BMP-7 transgenic hAECs exhibited the largest amount of matrix synthesis. In conclusion, these data indicate that BMP-7 plays an important role in inducing the production of cartilage by hAECs in vitro. Cartilage differentiation and matrix maturation can be promoted by BMPs in a cartilage engineering paradigm. These properties make BMPs promising tools in the engineering of cartilaginous joint bio-prostheses and as candidate biological agents or genes for cartilage stabilisation.

  1. Best Proximity Points of Contractive-type and Nonexpansive-type Mappings

    Directory of Open Access Journals (Sweden)

    R. Kavitha

    2018-02-01

    Full Text Available The purpose of this paper is to obtain best proximity point theorems for multivalued nonexpansive-type and contractive-type mappings on complete metric spaces and on certain closed convex subsets of Banach spaces. We obtain a convergence result under some assumptions and we prove the existence of common best proximity points for a sequence of multivalued contractive-type mappings.

  2. A Mediterranean-type diet is associated with better metabolic profile in urban Polish adults: Results from the HAPIEE study

    Science.gov (United States)

    Grosso, Giuseppe; Stepaniak, Urszula; Micek, Agnieszka; Topor-Mądry, Roman; Stefler, Denes; Szafraniec, Krystyna; Bobak, Martin; Pająk, Andrzej

    2015-01-01

    Objective The aim of this study was to evaluate the relationship between adherence to a Mediterranean-type diet and metabolic syndrome (MetS) in the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) cohort study. Materials/methods A cross-sectional survey including 8821 adults was conducted in Krakow, Poland. Food intake was evaluated through a validated food frequency questionnaire and adherence to the dietary pattern was assessed using a score specifically developed for non-Mediterranean countries (MedTypeDiet score). Linear and logistic regression models were performed to estimate beta and odds ratios (ORs) and 95% confidence intervals (CIs), respectively. Results Significant associations between the MedTypeDiet score and waist circumference (β = − 0.307 ± 0.239 cm), systolic blood pressure (β = − 0.440 ± 0.428 mmHg), and triglycerides (β = − 0.021 ± 0.016 mmol/L) were observed. After multivariable adjustment, individuals in the highest quartile of the score were less likely to have MetS, central obesity, high triglycerides, and hypertension. Increase of one standard deviation of the score was associated with 7% less odds of having MetS (OR 0.93, 95% CI: 0.88, 0.97). When analyzing the relation of single components of the MedTypeDiet score, wine, dairy products, and the total unsaturated:saturated fatty acids ratio were associated with MetS. Conclusions Adherence to a Mediterranean-like diet may decrease the risk of MetS also among non-Mediterranean populations. PMID:25752843

  3. Result from systematic compilation of barrel bolt findings in S/KWU type PWRs in the context of computational analysis

    International Nuclear Information System (INIS)

    Kilian, R.; Devrient, B.; Koenig, G.; Stanislowski, M.; Widera, M.; Beusekom, R. van; Wermelinger, T.

    2015-01-01

    In 2005 intergranular stress corrosion cracking (IGSCC) of barrel bolts was observed in several S/KWU type PWRs. The bolts, known as star bolts, are made of SS type 316 Ti (German Material No. 1.4571 K) bars which are cold worked to adjust the required mechanical properties. This damage mechanism was so far less understood for PWR primary conditions. Therefore an extended joint research program was launched by AREVA GmbH and VGB e.V. to clarify the specific conditions which contributed to the observed findings on barrel bolts. A systematic analysis of the IGSCC affecting parameters as material, heats, environment and mechanical load was performed based on a plant data compilation from all six S/KWU PWRs with comparable core barrel design using barrel and baffle bolts made from type 316Ti. Using the outcome of this systematic data compilation additional computational fluid dynamics calculations in combination with radiolysis calculations were performed. The results showed that by a combination of reduced volume exchange by local flow conditions and radiolysis reactions forming oxidizing species as dissolved oxygen and/or hydrogen peroxide may locally affect the corrosion behavior of cold worked austenitic stainless steels. Therefore, small local volumes with oxidizing water chemistry conditions are assumed to lead to the IGSCC of cold worked type 316Ti. The comparison of the initial cold worked microstructure by TEM with the cold worked and in service irradiated microstructure (void formation, dislocation loop density, etc.) clearly reveals that neutron irradiation hardening in terms of IASCC (Irradiation-Assisted Stress Corrosion Cracking) is not the leading mechanism for these cases of barrel bolt cracking in the analyzed PWRs. (authors)

  4. Influence of chamber type integrated with computer-assisted semen analysis (CASA) system on the results of boar semen evaluation.

    Science.gov (United States)

    Gączarzewicz, D

    2015-01-01

    The objective of the study was to evaluate the effect of different types of chambers used in computer-assisted semen analysis (CASA) on boar sperm concentration and motility parameters. CASA measurements were performed on 45 ejaculates by comparing three commonly used chambers: Leja chamber (LJ), Makler chamber (MK) and microscopic slide-coverslip (SL). Concentration results obtained with CASA were verified by manual counting on a Bürker hemocytometer (BH). No significant differences were found between the concentrations determined with BH vs. LJ and SL, whereas higher (p0.05). The results obtained show that CASA assessment of boar semen should account for the effect of counting chamber on the results of sperm motility and concentration, which confirms the need for further study on standardizing the automatic analysis of boar semen.

  5. Polarimetric survey of main-belt asteroids. II. Results for 58 B- and C-type objects

    Science.gov (United States)

    Gil-Hutton, R.; Cañada-Assandri, M.

    2012-03-01

    Aims: We present results of a polarimetric survey of main-belt asteroids at Complejo Astronómico el Leoncito (CASLEO), San Juan, Argentina. The aims of this survey are to increase the database of asteroid polarimetry, to estimate diversity in polarimetric properties of asteroids that belong to different taxonomic classes, and to search for objects that exhibit anomalous polarimetric properties. Methods: The data were obtained with the Torino and CASPROF polarimeters at the 2.15m telescope. The Torino polarimeter is an instrument that allows simultaneous measurement of polarization in five different bands, and the CASPROF polarimeter is a two-hole aperture polarimeter with rapid modulation. Results: The survey began in 2003, and up to 2009 data on a sample of more than 170 asteroids were obtained. In this paper the results for 58 B- and C-type objects are presented, most of them polarimetrically observed for the first time. Using these data we find phase-polarization curves and polarimetric parameters for these taxonomic classes. Based on observations carried out at the Complejo Astronómico El Leoncito, operated under agreement between the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina and the National Universities of La Plata, Córdoba, and San Juan.Tables 1 and 2 are available in electronic form at CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/539/A115

  6. Functional Results of Unstable (Type 2 Distal Clavicle Fractures Treated with Superior Anterior Locking Plate

    Directory of Open Access Journals (Sweden)

    Rajesh Govindasamy

    2017-11-01

    Full Text Available Background: The treatment of distal clavicle fracture is always a challenge, as it is mostly unstable and has higherrate of delayed union, malunion, non-union and associated acromioclavicular arthritis. So the management of thesefractures remains controversial. The purpose of this study is to evaluate the functional results of Type 2 distal endclavicle fractures treated with superior anterior locking plate.Methods: From June 2011 to August 2015 a retrospective study of12 male patients (mean age of 41.3 years 11 withunilateral and 1 with bilateral distal clavicle fractures treated with superior anterior locking plate was done. They wereevaluated at regular intervals with mean follow up of 14 months(12-18 months.Those with minimum one year followup were included in our study. All were evaluated for the functioning of the shoulder joint by both Oxford shoulder scoreand Quick DASH scores, rate of bone union, complications and earliest time for return to work.Results: All fractures union seen within 6-8 weeks (mean time: 7.1 weeks.All had good shoulder range of motion. Theaverage oxford shoulder and Quick DASH score were 46.2 and 6.5.There were no major complications in our studyviz. non-union, plate failure, secondary fracture. But one patient had superficial wound infection. All patients returned towork within 3 months of postoperative period.Conclusion: Displaced distal clavicle fractures treated with superior anterior locking plates achieved excellent resultsin terms of bony union with rarely any complications and demonstrate promising results with this novel technique.

  7. Proliferation and differentiation of stem cells in contact with eluate from fibrin-rich plasma membrane

    Directory of Open Access Journals (Sweden)

    Fernanda Gimenez de Souza

    Full Text Available ABSTRACT Objective: To evaluate the ability of the eluate from fibrin-rich plasma (FRP membrane to induce proliferation and differentiation of isolated human adipose-derived stem cells (ASCs into chondrocytes. Method: FRP membranes were obtained by centrifugation of peripheral blood from two healthy donors, cut, and maintained in culture plate wells for 48 h to prepare the fibrin eluate. The SCATh were isolated from adipose tissue by collagenase digestion solution, and expanded in vitro. Cells were expanded and treated with DMEM-F12 culture, a commercial media for chondrogenic differentiation, and eluate from FRP membrane for three days, and labeled with BrdU for quantitative assessment of cell proliferation using the High-Content Operetta® imaging system. For the chondrogenic differentiation assay, the SCATh were grown in micromass for 21 days and stained with toluidine blue and aggrecan for qualitative evaluation by light microscopy. The statistical analysis was performed using ANOVA and Tukey's test. Results: There was a greater proliferation of cells treated with the eluate from FRP membrane compared to the other two treatments, where the ANOVA test showed significance (p < 0.001. The differentiation into chondrocytes was visualized by the presence of mucopolysaccharide in the matrix of the cells marked in blue toluidine and aggrecan. Conclusions: Treatment with eluate from FRP membrane stimulated cell proliferation and induced differentiation of the stem cells into chondrocytes, suggesting a potential application of FRP membranes in hyaline cartilage regeneration therapies.

  8. Effect of angiotensin-converting enzyme gene polymorphism at the results of losartan use in the patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    T. Yu. Poniatowskaya

    2015-03-01

    Odessa National Medical University   Summary The article presented is an original investigation where the effects of losartan in patients with hypertension and type 2 diabetes mellitus (T2DM have been evaluated. The effect of therapy has been estimated with the help of gene ACE allelic variant. The dependence of enalapril antihypertensive action and nephroprotective action of ACE polymorphism has been revealed. The results obtained show a different effect on ACE allele variants of lipid metabolism in patients with hypertension and T2DM and complications in the form of hypertriglyceridemia in the patients with DD-genotype.   Key words: type 2 diabetes mellitus, hypertension, I / D polymorphism of the gene ACE, pharmacogenetics, losartan.

  9. The use of fibrin and poly(lactic-co-glycolic acid hybrid scaffold for articular cartilage tissue engineering: an in vivo analysis

    Directory of Open Access Journals (Sweden)

    S Munirah

    2008-02-01

    Full Text Available Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid (PLGA hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2 solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.

  10. Periodic heat shock accelerated the chondrogenic differentiation of human mesenchymal stem cells in pellet culture.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    Full Text Available Osteoarthritis (OA is one of diseases that seriously affect elderly people's quality of life. Human mesenchymal stem cells (hMSCs offer a potential promise for the joint repair in OA patients. However, chondrogenic differentiation from hMSCs in vitro takes a long time (∼ 6 weeks and differentiated cells are still not as functionally mature as primary isolated chondrocytes, though chemical stimulations and mechanical loading have been intensively studied to enhance the hMSC differentiation. On the other hand, thermal stimulations of hMSC chondrogenesis have not been well explored. In this study, the direct effects of mild heat shock (HS on the differentiation of hMSCs into chondrocytes in 3D pellet culture were investigated. Periodic HS at 41 °C for 1 hr significantly increased sulfated glycosaminoglycan in 3D pellet culture at Day 10 of chondrogenesis. Immunohistochemical and Western Blot analyses revealed an increased expression of collagen type II and aggrecan in heat-shocked pellets than non heat-shocked pellets on Day 17 of chondrogenesis. In addition, HS also upregulated the expression of collagen type I and X as well as heat shock protein 70 on Day 17 and 24 of differentiation. These results demonstrate that HS accelerated the chondrogenic differentiation of hMSCs and induced an early maturation of chondrocytes differentiated from hMSCs. The results of this study will guide the design of future protocols using thermal treatments to facilitate cartilage regeneration with human mesenchymal stem cells.

  11. Description of a novel approach to engineer cartilage with porous bacterial nanocellulose for reconstruction of a human auricle.

    Science.gov (United States)

    Feldmann, Eva-Maria; Sundberg, J F; Bobbili, B; Schwarz, S; Gatenholm, P; Rotter, N

    2013-11-01

    In this study, we investigated the effects of human primary chondrocytes, derived from routine septorhino- and otoplasties on a novel nondegradable biomaterial. This biomaterial, porous bacterial nanocellulose, is produced by Gluconacetobacter xylinus. Porosity is generated by paraffin beads embedded during the fermentation process. Human primary chondrocytes were able to adhere to bacterial nanocellulose and produce cartilaginous matrix proteins such as aggrecan (after 14 days) and collagen type II (after 21 days) in the presence of differentiation medium. Cells were located within the pores and in a dense cell layer covering the surface of the biomaterial. Cells were able to re-differentiate, as cell shape and extra cellular matrix gene expression showed a chondrogenic phenotype in three-dimensional bacterial nanocellulose culture. Collagen type I and versican expression decreased during three-dimensional culture. Variations in pore sizes of 150-300 µm and 300-500 µm did not influence cartilaginous extra cellular matrix synthesis. Varying seeding densities from 9.95 × 10(2) to 1.99 × 10(3) cells/mm(2) and 3.98 × 10(3) cells/mm(2) did not result in differences in quality of extra cellular matrix neo-synthesis. Our results demonstrated that both nasal and auricular chondrocytes are equally suitable to synthesize new extra cellular matrix on bacterial nanocellulose. Therefore, we propose both cell sources in combination with bacterial nanocellulose as promising candidates for the special needs of auricular reconstruction.

  12. Results of 1-year Diet and Exercise Interventions for ER+/PR±/HER2- Breast Cancer Patients Correlated with Treatment Type.

    Science.gov (United States)

    Artene, Diana V; Bordea, Cristian I; Blidaru, Alexandru

    2017-01-01

    Many breast cancer patients gain weight during chemotherapy and antiestrogenic treatment increasing recurrence, oncologic specific and all-cause mortality risks. Patients and Methods: 165 ER+/PR±/HER2- breast cancer patients under antiestrogenic treatment were randomly assigned to follow an at-home diet based on food naturally high in proteins, calcium, probiotics and prebiotics (D), or this diet and 4' isometric exercises (D+Ex) for 1 year. We measured weight (W), body (BF) and visceral fat (VF) using a multi-frequency bioelectrical impedance scale on the 6th and 12th month and we correlated results with chemotherapy, surgery and antiestrogenic medication type. Results were analysed using the Friedman Test, then with Wilcoxon signed-rank tests if Friedman Test was significant. Results: Overall, the patients 1-year results show that both D+Ex and D patients obtained statistically significant weight loss and fat loss. D patients lost 3.3 kg, 3.2% BF and 1% visceral fat. D+Ex patients lost 6.5 kg, 3.3% BF and 2% visceral fat. D+Ex patients obtained statistically significance for W, BF and VF regardless of chemotherapy, surgery or antiestrogenic treatment type. D patients with mastectomy or with aromatase inhibitors lost W, BF and VF. D patients with conservatory surgery, adjuvant or both neoadjuvant and adjuvant chemotherapy and those on Tamoxifen only lost W. D patients with neoadjuvant chemotherapy also lost VF. This diet is effective for ER+/PR±/HER2- breast cancer patients on antiestrogenic medication. Adding at least a minimal exercise protocol improves patients chances of counteracting sarcopenic obesity. Celsius.

  13. Relationships between hole type penetrameter sensitivities and wire type penetrameter sensitivities

    International Nuclear Information System (INIS)

    Iwahashi, Y.; Ebata, M.; Ooka, K.; Hirayama, K.; Senda, T.

    1985-01-01

    Radiographic investigations were conducted using the two types of penetrameters (hole and wire types) to obtain the relationships between hole type penetrameter sensitivities and wire type penetrameter sensitivities. Furthermore, the effects of radiation sources and kinds of X-ray films on the relationships were investigated. As a result, the quantitative relationship were defined. It was also clarified that the kinds of X-ray films and radiation sources have a relatively little effect on the relationship

  14. Type 2 diabetes prevention in the "real world": one-year results of the GOAL Implementation Trial.

    Science.gov (United States)

    Absetz, Pilvikki; Valve, Raisa; Oldenburg, Brian; Heinonen, Heikki; Nissinen, Aulikki; Fogelholm, Mikael; Ilvesmäki, Vesa; Talja, Martti; Uutela, Antti

    2007-10-01

    "Real-world" implementation of lifestyle interventions is a challenge. The Good Ageing in Lahti Region (GOAL) Lifestyle Implementation Trial was designed for the primary health care setting, with lifestyle and risk reduction objectives derived from the major diabetes prevention efficacy trials. We report on the program's effectiveness as well as findings related to the program's reach, adoption, and implementation. A total of 352 middle-aged participants with elevated type 2 diabetes risk were recruited from the health care centers in Päijät-Häme Province in Finland. The intervention included six group counseling sessions, delivered by trained public health nurses. Measurement was conducted at baseline and 12 months. Clinical risk factors were measured by study nurses, and lifestyle outcomes were analyzed from self-reports. Lifestyle outcomes were compared with the outcomes achieved in relevant efficacy trials, and within-subject changes were tested for risk reduction. At baseline, mean BMI was >32 kg/m2, and 25% of the participants had impaired glucose tolerance. At 12 months, 20% of participants achieved at least four of five key lifestyle outcomes, with these results being comparable with the reference trials. However, physical activity and weight loss goals were achieved significantly less frequently (65 vs. 86% and 12 vs. 43%, respectively). Several clinical risk factors decreased, more so among men than women. This trial demonstrates that lifestyle counseling can be effective and is feasible in real-world settings for individuals with elevated risk of type 2 diabetes. To increase program impact, program exposure and treatment intensity need to be increased.

  15. Psychological and personality factors in type 2 diabetes mellitus, presenting the rationale and exploratory results from The Maastricht Study, a population-based cohort study

    DEFF Research Database (Denmark)

    van Dooren, Fleur E P; Denollet, Johan; Verhey, Frans R J

    2016-01-01

    BACKGROUND: Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits...... in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly....... Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex...

  16. Is type-D personality trait(s or state? An examination of type-D temporal stability in older Israeli adults in the community

    Directory of Open Access Journals (Sweden)

    Ada H. Zohar

    2016-02-01

    Full Text Available Background. Type D personality was suggested as a marker of poorer prognosis for patients of cardiovascular disease. It is defined by having a score of 10 or more on both sub-scales of the DS14 questionnaire, Social Inhibition (SI and Negative Affectivity (NA. As Type D was designed to predict risk, its temporal stability is of prime importance. Methods. Participants in the current study were 285 community volunteers, who completed the DS14, and other personality scales, at a mean interval of six years. Results. The prevalence of Type D did not change. The component traits of Type D showed rank order stability. Type D caseness temporal stability was improved by using the sub-scales product as a criterion. Logistic hierarchical regression predicting Type D classification from Time1 demonstrated that the best predictors were Time1 scores on NA and SI, with the character trait of Cooperation, and the alexithymia score adding some predictive power. Conclusions. The temporal stability of the component traits, and of the prevalence of Type D were excellent. Temporal stability of Type D caseness may be improved by using a product threshold, rather than the current rule. Research is required in order to formulate the optimal timing for Type D measurement for predictive purposes.

  17. Magnesium Intake, Quality of Carbohydrates, and Risk of Type 2 Diabetes: Results From Three U.S. Cohorts.

    Science.gov (United States)

    Hruby, Adela; Guasch-Ferré, Marta; Bhupathiraju, Shilpa N; Manson, JoAnn E; Willett, Walter C; McKeown, Nicola M; Hu, Frank B

    2017-12-01

    Magnesium intake is inversely associated with risk of type 2 diabetes in many observational studies, but few have assessed this association in the context of the carbohydrate quality of the diet. We hypothesized that higher magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of a poor carbohydrate-quality diet characterized by low cereal fiber or high glycemic index (GI) or glycemic load (GL). In the Nurses' Health Study (NHS; 1984-2012, n = 69,176), NHS2 (1991-2013, n = 91,471), and the Health Professionals' Follow-Up Study (1986-2012, n = 42,096), dietary intake was assessed from food frequency questionnaires every 4 years. Type 2 diabetes was ascertained by biennial and supplementary questionnaires. We calculated multivariate hazard ratios (HRs) of magnesium intake and incident diabetes, adjusted for age, BMI, family history of diabetes, physical activity, smoking, hypertension, hypercholesterolemia, GL, energy intake, alcohol, cereal fiber, polyunsaturated fats, trans fatty acids, and processed meat, and we considered the joint associations of magnesium and carbohydrate quality on diabetes risk. We documented 17,130 incident cases of type 2 diabetes over 28 years of follow-up. In pooled analyses across the three cohorts, those with the highest magnesium intake had 15% lower risk of type 2 diabetes compared with those with the lowest intake (pooled multivariate HR in quintile 5 vs. 1: 0.85 [95% CI 0.80-0.91], P magnesium intake was more strongly associated with lower risk of type 2 diabetes among participants with high GI or low cereal fiber than among those with low GI or high cereal fiber (both P interaction magnesium intake is associated with lower risk of type 2 diabetes, especially in the context of lower carbohydrate-quality diets. © 2017 by the American Diabetes Association.

  18. Type Inference with Inequalities

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff

    1991-01-01

    of (monotonic) inequalities on the types of variables and expressions. A general result about systems of inequalities over semilattices yields a solvable form. We distinguish between deciding typability (the existence of solutions) and type inference (the computation of a minimal solution). In our case, both......Type inference can be phrased as constraint-solving over types. We consider an implicitly typed language equipped with recursive types, multiple inheritance, 1st order parametric polymorphism, and assignments. Type correctness is expressed as satisfiability of a possibly infinite collection...

  19. Results of safety analysis on PWR type nuclear power plants with two and three loops

    International Nuclear Information System (INIS)

    1979-01-01

    The results of safety analysis on PWR type nuclear power plants with two and three loops are presented, which was conducted by the Resource and Energy Agency, in June, 1979. This analysis was made simulating the phenomenon relating to the pressurizer level gauge at the time of the TMI accident. The model plants were the Ikata nuclear power plant with two loops and the Takahama No. 1 nuclear power plant with three loops. The premise conditions for this safety analysis were as follows: 1) the main feed water flow is totally lost suddenly at the full power operation of the plants, and the feed water pump is started manually 15 minutes after the accident initiation, 2) the relief valve on the pressurizer is kept open even after the pressure drop in the primary cooling system, and the primary cooling water flows out into the containment vessel through the rupture disc of the pressurizer relief tank, and 3) the electric circuit, which sends out the signal of safety injection at the abnormal low pressure in the reactor vessel, is added from the view-point of starting the operation of the emergency core cooling system as early as possible. Relating to the analytical results, the pressure in the reactor vessels changes less, the water level in the pressurizers can be regulated, and the water level in the steam generators is recovered safely in both two and three-loop plants. It is recognized that the plants with both two- and three loops show the safe transient phenomena, and the integrity of the cores is kept under the premise conditions. The evaluation for each analyzed result was conducted in detail. (Nakai, Y.)

  20. Synthesis and Characterization of a Chondroitin Sulfate Based Hybrid Bio/Synthetic Biomimetic Aggrecan Macromolecule

    Science.gov (United States)

    Sarkar, Sumona

    Lower back pain resulting from intervertebral disc degeneration is one of the leading musculoskeletal disorders confronting our health system. In order to mechanically stabilize the disc early in the degenerative cascade and prevent the need for spinal fusion surgeries, we have proposed the development of a hybrid-bio/synthetic biomimetic proteoglycan macromolecule for injection into the disc in the early stages of degeneration. The goal of this thesis was to incorporate natural chondroitin sulfate (CS) chains into bottle brush polymer synthesis strategies for the fabrication of CS-macromolecules which mimic the proteoglycan structure and function while resisting enzymatic degradation. Both the "grafting-to" and "grafting-through" techniques of bottle brush synthesis were explored. CS was immobilized via a terminal primary amine onto a model polymeric backbone (polyacrylic acid) for investigation of the "grafting-to" strategy and an epoxy-amine step-growth polymerization technique was utilized for the "grafting-through" synthesis of CS-macromolecules with polyethylene glycol backbone segments. Incorporation of a synthetic polymeric backbone at the terminal amine of CS was confirmed via biochemical assays, 1H-NMR and FTIR spectroscopy, and CS-macromolecule size was demonstrated to be higher than that of natural CS via gel permeation chromatography, transmission electron microscopy and viscosity measurements. Further analysis of CS-macromolecule functionality indicated maintenance of natural CS properties such as high fixed charge density, high osmotic potential and low cytotoxicity with nucleus pulposus cells. These studies are the first attempt at the incorporation of natural CS into biomimetic bottle brush structures. CS-macromolecules synthesized via the methods developed in these studies may be utilized in the treatment and prevention of debilitating back pain as well as act as mimetics for other proteoglycans implicated in cartilage, heart valve, and nervous

  1. Fracture risk in women with type II diabetes. Results from a historical cohort with fracture follow-up

    DEFF Research Database (Denmark)

    Holm, Jakob Præst; Jensen, Thomas; Hyldstrup, Lars

    2018-01-01

    . Prevalent fractures (43.7 vs. 33.2%, p = 0.0010) and prevalent MOF (26.2 vs. 20.5% p = 0.038) were more common among patients with type II diabetes. The unadjusted incident fracture risk was increased with a higher relative risk of 42%. An elevated MOF hazard ratio was present (HR = 1.726, p = 0.......0006). Adjustment for prevalent osteoporosis and other possible confounders did not change this finding (HR = 1.558, p = 0.0207). CONCLUSIONS: An association between type II diabetes and an increased risk of MOF primarily driven by an increased hip fracture risk was documented. This finding was independent......PURPOSE: To examine the independent association between type II diabetes and fracture risk in a population of predominantly postmenopausal women referred to a specialist clinic for osteoporosis evaluation. METHODS: Type II diabetes associated fracture risk were evaluated among to 229 patients...

  2. Comparative study on the treatment of Rockwood type III acute acromioclavicular dislocation: Clinical results from the TightRope® technique vs. K-wire fixation.

    Science.gov (United States)

    Horst, K; Garving, C; Thometzki, T; Lichte, P; Knobe, M; Dienstknecht, T; Hofman, M; Pape, H-C

    2017-04-01

    The aim of this study was to address the inconsistency regarding the operative treatment of Rockwood type III acromioclavicular joint separation. We compared results after single- and double TightRope ® reduction with results after acromioclavicular transfixation via K-wires only and additional ligament augmentation in acute acromioclavicular (AC) joint separations graded Rockwood type III, and hypothesized that the TightRope ® technique leads to better clinical and radiological results. We conducted a retrospective clinical cohort study and included 42 consecutive patients (mean age 43 years [24-66]) diagnosed and operatively treated between 2004 and 2012 (mean follow-up was 54.6 months [15-118]). Specific shoulder scores as well as scores reflecting the patients' overall mental and physical health status were used. Radiological evaluation was also performed. The SF12 test revealed comparability between all subgroups. Specific shoulder tests and a visual analogue scale demonstrated comparable results. Radiographic measurements showed a significant reduction in the AC distance and CC distance after surgery in all subgroups. The early complication rate was 9.5% for all patients, while late complications occurred in 14.3% of all cases. Compared to the established methods, the operative TightRope ® procedures represent a safe alternative in Rockwood III injuries. All investigated techniques predominantly led to good and excellent clinical results in acute Rockwood type III AC joint instabilities. Avoidance of material removal and shorter hospital stays appear to speak in favour for the TightRope ® technique. IV. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.

    Science.gov (United States)

    Zhang, Zhuo; Leong, Daniel J; Xu, Lin; He, Zhiyong; Wang, Angela; Navati, Mahantesh; Kim, Sun J; Hirsh, David M; Hardin, John A; Cobelli, Neil J; Friedman, Joel M; Sun, Hui B

    2016-06-03

    Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan

  4. Molecular typing of methicillin-resistant Staphylococcus aureus: Comparison of PCR-based open reading frame typing, multilocus sequence typing, and Staphylococcus protein A gene typing.

    Science.gov (United States)

    Ogihara, Shinji; Saito, Ryoichi; Sawabe, Etsuko; Kozakai, Takahiro; Shima, Mari; Aiso, Yoshibumi; Fujie, Toshihide; Nukui, Yoko; Koike, Ryuji; Hagihara, Michio; Tohda, Shuji

    2018-04-01

    The recently developed PCR-based open reading frame typing (POT) method is a useful molecular typing tool. Here, we evaluated the performance of POT for molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) isolates and compared its performance to those of multilocus sequence typing (MLST) and Staphylococcus protein A gene typing (spa typing). Thirty-seven MRSA isolates were collected between July 2012 and May 2015. MLST, spa typing, and POT were performed, and their discriminatory powers were evaluated using Simpson's index analysis. The MRSA isolates were classified into 11, 18, and 33 types by MLST, spa typing, and POT, respectively. The predominant strains identified by MLST, spa typing, and POT were ST8 and ST764, t002, and 93-191-127, respectively. The discriminatory power of MLST, spa typing, and POT was 0.853, 0.875, and 0.992, respectively, indicating that POT had the highest discriminatory power. Moreover, the results of MLST and spa were available after 2 days, whereas that of POT was available in 5 h. Furthermore, POT is rapid and easy to perform and interpret. Therefore, POT is a superior molecular typing tool for monitoring nosocomial transmission of MRSA. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  5. Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device

    Directory of Open Access Journals (Sweden)

    Susanne Johansson

    2007-01-01

    Full Text Available The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector. CEA was expressed either in a membrane-bound form (wild-type CEA or in two truncated forms (CEA6 and CEA66 with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response.

  6. Sun protection attitudes and behaviours among first generation Australians with darker skin types: results from focus groups.

    Science.gov (United States)

    Bryant, Jamie; Zucca, Alison; Brozek, Irena; Rock, Vanessa; Bonevski, Billie

    2015-02-01

    Despite residing in a country that has the highest rates of skin cancer in the world, little is known about the knowledge, attitudes and sun protection practices of first generation Australian-born individuals with olive and darker skin types. Six focus groups with first generation Australian-born individuals of Asian, Mediterranean, Middle Eastern and Indian background were conducted. Participants had good knowledge of the dangers of skin cancer. Most correctly perceived darker skin types as protective and believed they were at low risk of skin cancer. Most participants could recall high profile mass media sun protection campaigns. Several participants suggested that greater representation of ethnic minorities and/or individuals with darker skin types would increase the personal relevance of campaigns. Beliefs that sun protection is not necessary on the basis of skin type highlights the need for further studies to explore fundamental differences in attitudes and practices between those with olive and darker skin and the general Australian population.

  7. Analytic two-loop results for self-energy- and vertex-type diagrams with one non-zero mass

    International Nuclear Information System (INIS)

    Fleischer, J.; Kotikov, A.V.; Veretin, O.L.

    1999-01-01

    For a large class of two-loop self-energy- and vertex-type diagrams with only one non-zero mass (m) and the vertices also with only one non-zero external momentum squared (q 2 ) the first few expansion coefficients are calculated by the large mass expansion. This allows us to 'guess' the general structure of these coefficients and to verify them in terms of certain classes of 'basis elements', which are essentially harmonic sums. Since for this case with only one non-zero mass the large mass expansion and the Taylor series in terms of q 2 are identical, this approach yields analytic expressions of the Taylor coefficients, from which the diagram can be easily evaluated numerically in a large domain of the complex q 2 -plane by well known methods. It is also possible to sum the Taylor series and present the results in terms of polylogarithms

  8. Cardiovascular responses in type A and type B men to a series of stressors.

    Science.gov (United States)

    Ward, M M; Chesney, M A; Swan, G E; Black, G W; Parker, S D; Rosenman, R H

    1986-02-01

    Fifty-six healthy adult males were administered the Type A Structured Interview and assessed as exhibiting either Type A (N = 42) or Type B (N = 14) behavior pattern. They were monitored for systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) responses during a series of six challenging tasks: Mental Arithmetic, Hypothesis Testing, Reaction Time, Video Game, Handgrip, and Cold Pressor. The results indicated that Type A subjects exhibited greater cardiovascular responses than did Type B subjects during some (Hypothesis Testing, Reaction Time, Video Game and Mental Arithmetic) but not all (Handgrip and Cold Pressor) of the tasks. These results are discussed in terms of previously reported findings on conditions that do and do not produce differences in Type A/B cardiovascular stress responses.

  9. Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands

    DEFF Research Database (Denmark)

    Pouwer, F; Geelhoed-Duijvestijn, P H L M; Tack, C J

    2010-01-01

    AIMS: Depression is common in diabetes, but the scope of the problem and associated correlates are not well established in specialist diabetes care. We aimed to determine the prevalence of depression among adult outpatients with Type 1 (T1DM) or Type 2 diabetes (T2DM) using both self...

  10. Resource consumption and costs in Dutch patients with Type 2 diabetes mellitus. Results from 29 general practices

    NARCIS (Netherlands)

    Redekop, WK; Koopmanschap, MA; Rutten, GEHM; Wolffenbuttel, BHR; Stolk, RP; Niessen, LW

    Aims The aims of this study were to estimate the costs incurred by Dutch patients with Type 2 diabetes, examine which patient and/or treatment characteristics are associated with costs, and estimate the medical and non-medical costs of patients with Type 2 diabetes in The Netherlands. Methods

  11. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    Visser, G.; Rake, J.P.; Labrune, P.; Leonard, J.V.; Moses, S.; Ullrich, K.; Wendel, U.; Groenier, K.H.; Smit, G.P.

    2002-01-01

    Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in

  12. Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands.

    NARCIS (Netherlands)

    Pouwer, F.; Geelhoed-Duijvestijn, P.H.; Tack, C.J.J.; Bazelmans, E.; Beekman, A.J.; Heine, R.J.; Snoek, F.J.

    2010-01-01

    AIMS: Depression is common in diabetes, but the scope of the problem and associated correlates are not well established in specialist diabetes care. We aimed to determine the prevalence of depression among adult outpatients with Type 1 (T1DM) or Type 2 diabetes (T2DM) using both self-report measures

  13. Prevalence of comorbid depression is high in out-patients with Type 1 or Type 2 diabetes mellitus. Results from three out-patient clinics in the Netherlands

    NARCIS (Netherlands)

    Pouwer, F.; Geelhoed-Duijvestijn, P.H.L.M.; Tack, C.J.; Bazelmans, E.; Beekman, A.T.F.; Heine, R.J.; Snoek, F.J.

    2010-01-01

    Aims Depression is common in diabetes, but the scope of the problem and associated correlates are not well established in specialist diabetes care. We aimed to determine the prevalence of depression among adult outpatients with Type 1 (T1DM) or Type 2 diabetes (T2DM) using both self-report measures

  14. Delta-like 1/fetal antigen-1 (Dlk1/FA1) is a novel regulator of chondrogenic cell differentiation via inhibition of the Akt kinase-dependent pathway

    DEFF Research Database (Denmark)

    Chen, Li; Qanie, Diyako; Jafari, Abbas

    2011-01-01

    Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects...... on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified......, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1...

  15. Clinical Results of 40 Consecutive Basal Thumb Prostheses and No CRPS Type I After Vitamin C Prophylaxis.

    Science.gov (United States)

    Zollinger, Paul E; Unal, Halil; Ellis, Maarten L; Tuinebreijer, Wim E

    2010-02-17

    Complex regional pain syndrome (CRPS) type I may occur as complication after any type of surgery for basal joint arthritis of the thumb. We investigated prospectively in an ongoing study our results after a fully standardized treatment with a total joint prosthesis under vitamin C prophylaxis.Patients with trapeziometacarpal arthritis stage II or III according to Dell, and no benefit from conservative treatment, were selected to undergo joint replacement with a semi-constrained hydroxyapatite coated prosthesis.First web opening and visual analogue scale (VAS) scores for pain, activities of daily living (ADL) and satisfaction were taken pre and postoperatively. Vitamin C 500 mg daily was started two days prior to surgery during 50 days as prevention for CRPS. Post-operative treatment was functional.We performed 40 implantations for trapeziometacarpal arthritis in 34 patients (mean age 60.8 years; 27 females, 7 males) with a mean follow-up of 44 months. Operations were performed in day care under regional (or general) anesthesia.First web opening increased with 15.4 degrees and there was a significant improvement for pain, ADL and satisfaction as well (p = 0.000). Patient satisfaction was strongly associated with the amount of pain reduction. According to the Veldman and IASP criteria, there were no cases of CRPS.The overall complication rate for this procedure is high. Literature reports 5 cases of CRPS after 38 operations with the same implant (13%). We advise vitamin C as prophylaxis against CRPS in trapeziometacarpal joint replacement.

  16. Efficacy of genital T cell responses to herpes simplex virus type 2 resulting from immunization of the nasal mucosa

    International Nuclear Information System (INIS)

    Milligan, Gregg N.; Dudley-McClain, Kristen L.; Chu Chinfun; Young, Christal G.

    2004-01-01

    Intravaginal (ivag) or intranasal (i.n.) immunization of C57BL/6J (B6) mice with a thymidine kinase-deficient strain (tk-) of herpes simplex virus type 2 (HSV-2) resulted in comparable protection of the genital epithelium and sensory ganglia against HSV-2 challenge. In contrast, protection of these sites was much reduced in i.n.-immunized compared to ivag-immunized B cell-deficient μMT mice. Fewer HSV-specific T cells were detected in the genital epithelium of i.n.-immunized compared to ivag-immunized μMT mice after HSV-2 challenge. Passive transfer of HSV-specific serum to immune μMT mice restored protection of these sites against HSV-2 challenge. These results suggest that protection of genital and neuronal sites may be conferred by i.n. immunization but may be more dependent on antibody-dependent mechanisms than the protection resulting from genital immunization. These results have implications for immunization strategies to elicit high levels of cell-mediated protection of the genital tract and sensory ganglia

  17. Viscoelastic response of a model endothelial glycocalyx

    International Nuclear Information System (INIS)

    Nijenhuis, Nadja; Spaan, Jos A E; Mizuno, Daisuke; Schmidt, Christoph F

    2009-01-01

    Many cells cover themselves with a multifunctional polymer coat, the pericellular matrix (PCM), to mediate mechanical interactions with the environment. A particular PCM, the endothelial glycocalyx (EG), is formed by vascular endothelial cells at their luminal side, forming a mechanical interface between the flowing blood and the endothelial cell layer. The glycosaminoglycan (GAG) hyaluronan (HA) is involved in the main functions of the EG, mechanotransduction of fluid shear stress and molecular sieving. HA, due to its length, is the only GAG in the EG or any other PCM able to form an entangled network. The mechanical functions of the EG are, however, impaired when any one of its components is removed. We here used microrheology to measure the effect of the EG constituents heparan sulfate, chondroitin sulfate, whole blood plasma and albumin on the high-bandwidth mechanical properties of a HA solution. Furthermore, we probed the effect of the hyaldherin aggrecan, a constituent of the PCM of chondrocytes, and very similar to versican (present in the PCM of various cells, and possibly in the EG). We show that components directly interacting with HA (chondroitin sulfate and aggrecan) can increase the viscoelastic shear modulus of the polymer composite

  18. Predictors of adherence with self-care guidelines among persons with type 2 diabetes: results from a logistic regression tree analysis.

    Science.gov (United States)

    Yamashita, Takashi; Kart, Cary S; Noe, Douglas A

    2012-12-01

    Type 2 diabetes is known to contribute to health disparities in the U.S. and failure to adhere to recommended self-care behaviors is a contributing factor. Intervention programs face difficulties as a result of patient diversity and limited resources. With data from the 2005 Behavioral Risk Factor Surveillance System, this study employs a logistic regression tree algorithm to identify characteristics of sub-populations with type 2 diabetes according to their reported frequency of adherence to four recommended diabetes self-care behaviors including blood glucose monitoring, foot examination, eye examination and HbA1c testing. Using Andersen's health behavior model, need factors appear to dominate the definition of which sub-groups were at greatest risk for low as well as high adherence. Findings demonstrate the utility of easily interpreted tree diagrams to design specific culturally appropriate intervention programs targeting sub-populations of diabetes patients who need to improve their self-care behaviors. Limitations and contributions of the study are discussed.

  19. Effect of chondrocyte-derived early extracellular matrix on chondrogenesis of placenta-derived mesenchymal stem cells.

    Science.gov (United States)

    Park, Yong-Beom; Seo, Sinji; Kim, Jin-A; Heo, Jin-Chul; Lim, Young-Cheol; Ha, Chul-Won

    2015-06-24

    The extracellular matrix (ECM) surrounding cells contains a variety of proteins that provide structural support and regulate cellular functions. Previous studies have shown that decellularized ECM isolated from tissues or cultured cells can be used to improve cell differentiation in tissue engineering applications. In this study we evaluated the effect of decellularized chondrocyte-derived ECM (CDECM) on the chondrogenesis of human placenta-derived mesenchymal stem cells (hPDMSCs) in a pellet culture system. After incubation with or without chondrocyte-derived ECM in chondrogenic medium for 1 or 3 weeks, the sizes and wet masses of the cell pellets were compared with untreated controls (hPDMSCs incubated in chondrogenic medium without chondrocyte-derived ECM). In addition, histologic analysis of the cell pellets (Safranin O and collagen type II staining) and quantitative reverse transcription-PCR analysis of chondrogenic markers (aggrecan, collagen type II, and SOX9) were carried out. Our results showed that the sizes and masses of hPDMSC pellets incubated with chondrocyte-derived ECM were significantly higher than those of untreated controls. Differentiation of hPDMSCs (both with and without chondrocyte-derived ECM) was confirmed by Safranin O and collagen type II staining. Chondrogenic marker expression and glycosaminoglycan (GAG) levels were significantly higher in hPDMSC pellets incubated with chondrocyte-derived ECM compared with untreated controls, especially in cells precultured with chondrocyte-derived ECM for 7 d. Taken together, these results demonstrate that chondrocyte-derived ECM enhances the chondrogenesis of hPDMSCs, and this effect is further increased by preculture with chondrocyte-derived ECM. This preculture method for hPDMSC chondrogenesis represents a promising approach for cartilage tissue engineering.

  20. Subset selection from Type-I and Type-II generalized logistic populations

    NARCIS (Netherlands)

    Laan, van der M.J.; Laan, van der P.

    1996-01-01

    We give an introduction to the logistic and generalized logistic distributions. We obtain exact results for the probability of correct selection from Type-I and Type-II generalized logistic populations which only differ in their location parameter. Some open problems are formulated.

  1. Results of the surgical correction of urinary stress incontinence according to the type of transobturator tape utilized

    Directory of Open Access Journals (Sweden)

    Bárbara Padilla-Fernández

    2013-09-01

    Full Text Available Objectives: To analyze the short and long term results of tapes of different materials used to treat stress urinary incontinence (SUI. A secondary objective was to evaluate the ability to adjust the tape after implantation. Materials and methods: Retrospective chart review of 355 patients with SUI operated between March 2003 and October 2011. Eight different types of transobturator tapes were used: Gynecare TVT-O®, Monarc®, SAFYRE®, Contasure KIM®, I-Stop®, DynaMesh®, Aris® Bandellete and Swing-band®. Results and complications were recorded. Results: The mean age at operation was 61 years. Correction of SUI was achieved in 87.88% of cases. The best results were obtained with Contasure KIM® (98.26 % continence. The tape was well tolerated and was elastic enough to be able to be adjusted 48-72 hours after implantation without deformation. Slings with macropores and over lock stiches on the superior and inferior borders presented the lower rates of postoperative urinary retention, pain, perior postoperative bleeding and urinary tract infections. Conclusions: Transobturator tension free tapes require a short operation time and have a low complication rate. The possibility of adjustment in the early postoperative period increases the success rate and reduces complications. Knotless meshes with macropores and over lock stiches appear to be better balanced, are quite resistant to stretching and deformation when readjusted after implantation and present a low infection rate.

  2. Type D (distressed) personality in primary care patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Nefs, Giesje; Pouwer, Francois; Pop, Victor J M

    2012-01-01

    D Scale-14 (DS14) in type 2 diabetes patients. METHODS: 1553 primary care patients with type 2 diabetes were assessed for demographic, clinical, lifestyle and psychological characteristics in 2007. A subgroup (n=1012) completed the DS14 again 1 year later. RESULTS: The two-factor model of the Type D...... or physiological risk factors, but Type D women had a more sedentary lifestyle (p=.003). Type D patients experienced less social support and more stressful life events, loneliness, and more depressed mood, anhedonia and anxiety (p0......OBJECTIVE: In cardiovascular research, Type D personality (high negative affectivity and social inhibition) has been associated with a more than 3-fold increased risk of adverse health outcomes. This study examined the validity and clinical correlates of the Type D construct as assessed by the Type...

  3. Niacin results in reduced monocyte adhesion in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Tavintharan, S; Woon, K; Pek, L T; Jauhar, N; Dong, X; Lim, S C; Sum, C F

    2011-03-01

    Patients with type 2 diabetes have increased expression of cell adhesion molecules (CAMs). CAMs and monocyte adhesion mediate essential processes in atherogenesis. It remains unclear if monocytes from patients on niacin have reduced adhesion function. We studied the variation of monocyte adhesion in patients with type 2 diabetes and low HDL-cholesterol, taking either extended release niacin (Niaspan®, Abbott Laboratories) or controls not on niacin. Biochemical parameters including adiponectin, CAMs and fresh monocytes from whole blood for adhesion assays, were studied at baseline and 12-weeks. Niacin 1500 mg daily raised HDL-cholesterol from 0.8 mmol/l (95% CI: 0.7-0.9) to 0.9 mmol/l (95% CI: 0.8-1.1), p=0.10, and significantly reduced PECAM-1 by 24.9% (95% CI: 10.9-39.0; p<0.05), increased adiponectin by 30.5% (95% CI: 14.1-47.0; p<0.05), with monocyte adhesion reduced by 9.2% (95%CI: 0.7-17.7; p<0.05) in endothelial cells treated in basal conditions, and 7.8% (95% CI: 3.1-12.5; p<0.05) after TNF-α stimulation. Monocytes isolated from patients on niacin had reduced adhesion to endothelial cells. Our findings suggest niacin has broad range of effects apart from lipid-modification, and these could be important in cardiovascular risk reduction. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Psychological and personality factors in type 2 diabetes mellitus, presenting the rationale and exploratory results from The Maastricht Study, a population-based cohort study.

    Science.gov (United States)

    van Dooren, Fleur E P; Denollet, Johan; Verhey, Frans R J; Stehouwer, Coen D A; Sep, Simone J S; Henry, Ronald M A; Kremers, Stef P J; Dagnelie, Pieter C; Schaper, Nicolaas C; van der Kallen, Carla J H; Koster, Annemarie; Pouwer, Frans; Schram, Miranda T

    2016-01-27

    Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice. We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level. Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83-3.60), 1.50 (0.72-3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23-3.10), 1.35 (0.93-1.94) and 1.70 (1.14-2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small. Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals

  5. A Kantorovich Type of Szasz Operators Including Brenke-Type Polynomials

    Directory of Open Access Journals (Sweden)

    Fatma Taşdelen

    2012-01-01

    convergence properties of these operators by using Korovkin's theorem. We also present the order of convergence with the help of a classical approach, the second modulus of continuity, and Peetre's -functional. Furthermore, an example of Kantorovich type of the operators including Gould-Hopper polynomials is presented and Voronovskaya-type result is given for these operators including Gould-Hopper polynomials.

  6. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nathella Pavan Kumar

    Full Text Available Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB, their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL and latent tuberculosis (LTB have not been well studied.To identify cytokine responses associated with pulmonary tuberculosis (TB, TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA.PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2; Type 2 (IL-4 and Type 17 (IL-17A and IL-17F cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially the suppression of cytokine responses in PTB.Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.

  7. Differentiation of human mesenchymal stromal cells cultured on collagen sponges for cartilage repair.

    Science.gov (United States)

    Sanjurjo-Rodríguez, Clara; Martínez-Sánchez, Adela Helvia; Hermida-Gómez, Tamara; Fuentes-Boquete, Isaac; Díaz-Prado, Silvia; Blanco, Francisco J

    2016-11-01

    The aim of this study was to evaluate proliferation and chondrogenic differentiation of human bone-marrow mesenchymal stromal cells (hBMSCs) cultured on collagen biomaterials. hBMSCs were seeded on five different collagen (Col) sponges: C1C2 (types I and II Col), C1C2HS (types I and II Col plus heparan sulphate (HS)), C1C2CHS (types I and II Col plus chondroitin sulphate (CHS)), C1-OLH3 (type I Col plus low molecular weight heparin) and C1CHS (type I Col plus CHS). The resulting constructs were analyzed by histological and immunohistochemical staining, molecular biology and electron microscopy. Col released into culture media was measured by a dye-binding method Results: hBMSCs on biomaterials C1C2, C1C2HS and C1C2CHS had more capacity to attach, proliferate and synthesize Col II and proteoglycans in the extracellular matrix (ECM) than on C1-OLH3 and C1CHS. The presence of aggrecan was detected only at the gene level. Total Col liberated by the cells in the supernatants in all scaffold cultures was detected. The level of Col I in the ECM was lower in C1-OLH3 and that of Col II was highest in C1C2 and C1C2HS. Electron microscopy showed differently shaped cells, from rounded to flattened, in all constructs. Col fibers in bundles were observed in C1C2CHS by transmission electron microscopy. The results show that Col I and Col II (C1C2, C1C2HS and C1C2CHS) biomaterials allowed cell proliferation and chondrogenic-like differentiation of hBMSCs at an early stage. Constructs cultured on C1C2HS and C1C2CHS showed better cartilage-like phenotype than the other ones.

  8. Effects of substrate type and arsenic dosage level on arsenic behavior in grassland microcosms. Part I. Preliminary results on 74As transport

    International Nuclear Information System (INIS)

    Draggan, S.

    1977-01-01

    Microcosm design is an important factor in interpreting results obtained from studies of the environmental effects, mobility and persistence of contaminants. The behavior of pentavalent arsenic and a radioarsenic tracer was studied in three substrate types exposed to differing levels of stable As dosage. Soil cores excised intact from a natural grassland ecosystem were considered to most reliably represent the natural system under study since they retained the soil structure, and closely simulated the abiotic and biotic complexity, of the grassland ecosystem. The behavior of 74 As in the components of intact soil core microcosms differed appreciably from that observed for the other microcosm types where soil underwent manipulation. These differences were explained primarily on the basis of differences in soil structure

  9. Abdominal visceral fat accumulation is associated with the results of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients

    Energy Technology Data Exchange (ETDEWEB)

    Anan, Futoshi [Oita Red Cross Hospital, Department of Cardiology, Oita (Japan); Oita University, Department of Internal Medicine I, Oita (Japan); Masaki, Takayuki; Takahashi, Naohiko; Yoshimatsu, Hironobu [Oita University, Department of Internal Medicine I, Oita (Japan); Yonemochi, Hidetoshi; Nakagawa, Mikiko; Saikawa, Tetsunori [Oita University, Department of Cardiovascular Science, Oita (Japan); Eshima, Nobuoki [Oita University, Department of Biostatistics, School of Medicine, Oita (Japan)

    2007-08-15

    We tested the hypothesis that increased abdominal visceral accumulation (VFA) is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The study group consisted of 24 type 2 diabetic patients with high VFA ({>=}100 cm{sup 2}, age 60 {+-} 8 years, high VFA group). The control group consisted of 19 age-matched type 2 diabetic patients with normal VFA (<100 cm{sup 2}, age 60 {+-} 7 years, normal VFA group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Early and delayed {sup 123}I-MIBG myocardial uptake values were lower (p < 0.005 and p < 0.0001, respectively) and the percent washout rate of {sup 123}I-MIBG was higher (p < 0.0005) in the high VFA group than in the normal VFA group. The fasting plasma insulin concentrations (p < 0.005) and the homeostasis model assessment (HOMA) index values (p < 0.0005) were higher in the high VFA group than in normal VFA group. Multiple regression analysis revealed that the level of VFA was independently predicted by the HOMA index values and the myocardial uptake of {sup 123}I-MIBG during the delayed phase. Our results demonstrate that the level of VFA is associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus. (orig.)

  10. The results of randomized controlled trial of low-dose radiation for wet-type age-related macular degeneration on a 1 year term basis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-06-01

    Evaluation of low dose radiation therapy to the wet-type age-related macular degeneration (AMD) located at the fovea centralis. Patients were irradiated with 10 fractions of 2 Gy external beam or just observed. Between the treated (39) and untreated (31) cases, there was no significant difference in gender, age, initial visual acuity, or size of the neovascular membrane. With the follow-up of 12 months, the visual acuity was significantly well preserved and the size of the neovascular membrane was decreased. These results indicate that low dose irradiation is effective for the wet-type AMD of the stage we treated in the present study. (author)

  11. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant.

    Science.gov (United States)

    Bartz, Christoph; Meixner, Miriam; Giesemann, Petra; Roël, Giulietta; Bulwin, Grit-Carsta; Smink, Jeske J

    2016-11-15

    Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don's chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany. Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential

  12. Results of a bone splint technique for the treatment of lower limb deformities in children with type I osteogenesis imperfecta

    Directory of Open Access Journals (Sweden)

    Dasheng Lin

    2013-01-01

    Full Text Available Background: Children with osteogenesis imperfecta (OI can suffer from frequent fractures and limb deformities, resulting in impaired ambulation. Osteopenia and thin cortices complicate orthopedic treatment in this group. This study evaluates the clinical results of a bone splint technique for the treatment of lower limb deformities in children with type I OI. The technique consists of internal plating combined with cortical strut allograft fixation. Materials and Methods: We prospectively followed nine children (five boys, four girls with lower limb deformities due to type I OI, who had been treated with the bone splint technique (11 femurs, four tibias between 2003 and 2006. The fracture healing time, deformity improvement, ambulation ability and complications were recorded to evaluate treatment effects. Results: At the time of surgery the average age in our study was 7.7 years (range 5-12 years. The average length of followup was 69 months (range 60-84 months. All patients had good fracture healing with an average healing time of 14 weeks (range 12-16 weeks and none experienced further fractures, deformity, or nonunion. The fixation remained stable throughout the procedure in all cases, with no evidence of loosening or breakage of screws and the deformity and mobility significantly improved after surgery. Of the two children confined to bed before surgery, one was able to walk on crutches and the other needed a wheelchair. The other seven patients could walk without walking aids or support like crutches. Conclusions: These findings suggest that the bone splint technique provides good mechanical support and increases the bone mass. It is an effective treatment for children with OI and lower limb deformities.

  13. Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

    Science.gov (United States)

    Han, Xiaorui; Leng, Xiaoming; Zhao, Man; Wu, Mei; Chen, Amei; Hong, Guoju; Sun, Ping

    2017-12-22

    Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration. © 2017 The Author(s).

  14. Study of differential properties of fibrochondrocytes and hyaline chondrocytes in growing rabbits.

    Science.gov (United States)

    Huang, L; Li, M; Li, H; Yang, C; Cai, X

    2015-02-01

    We aimed to build a culture model of chondrocytes in vitro, and to study the differential properties between fibrochondrocytes and hyaline chondrocytes. Histological sections were stained with haematoxylin and eosin so that we could analyse the histological structure of the fibrocartilage and hyaline cartilage. Condylar fibrochondrocytes and femoral hyaline chondrocytes were cultured from four, 4-week-old, New Zealand white rabbits. The production of COL2A1, COL1OA1, SOX9 and aggrecan was detected by real time-q polymerase chain reaction (RT-qPCR) and immunoblotting and the differences between them were compared statistically. Histological structures obviously differed between fibrocartilage and hyaline cartilage. COL2A1 and SOX9 were highly expressed within cell passage 2 (P2) of both fibrochondrocytes and hyaline chondrocytes, and reduced significantly after cell passage 4 (P4). The mRNA expressions of COL2A1 (p=0.05), COL10A1 (p=0.04), SOX9 (p=0.03), and aggrecan (p=0.04) were significantly higher in hyaline chondrocytes than in fibrochondrocytes, whereas the expression of COL1A1 (p=0.02) was the opposite. Immunoblotting showed similar results. We have built a simple and effective culture model of chondrocytes in vitro, and the P2 of chondrocytes is recommended for further studies. Condylar fibrocartilage and femoral hyaline cartilage have unique biological properties, and the regulatory mechanisms of endochondral ossification for the condyle should be studied independently in the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

    Directory of Open Access Journals (Sweden)

    I. V. Vorobyova

    2014-10-01

    Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

  16. The results of diagnostic and treatment of patients with diabetic retinopathy and age-related macular degeneration at a diabetes type 2.

    Directory of Open Access Journals (Sweden)

    I. V. Vorobyova

    2014-01-01

    Full Text Available Purpose: Explore the changing clinical and functional and morphological changes of the retina against application of angiogenesis inhibitor in patients with diabetes type 2 with comorbidity fundus: diabetic retinopathy (DR and agerelated macular degeneration (AMD.Patients and Methods. In the main study group included 22 patients (22 eyes with type 2 diabetes with combined fundus pathology DR and AMD. All patients before and after intravitreal injection of an angiogenesis inhibitor ranibizumab (Lucentis, Novartis was assessed visual acuity, macular thickness and macular morphology based on the results of OCT, the retinal sensitivity according to the data of microperimetry (MAIA. The control group study included 30 people (15 healthy and 15 with type 2 diabetes without DR.Results. When comparing the main group with the control group was revealed that visual acuity in the main group (0,27±0,05 was significantly lower than in the control group (0,8±0,01, p <0.05; retinal thickness was significantly higher in the control group, and the retinal sensitivity was significantly lower. On the background of intravitreal injection of ranibizumab all patients with DR and AMD had significantly increase in visual acuity on average by 37 % (from 0,27±0,05 before treatment to 0,37±0,05 after treatment, a significantly reduction of macular thickness in 9 out of 9 areas, including the fovea centralis, an average of 32.6 % and increase retinal sensitivity by 24 % (from 11,75±1,68 (dB to 14,58±1,68 (dB, (p <0.05. The correlations were found between visual acuity and retinal thickness, as well as between visual acuity and retinal sensitivity of the macula, before treatment r = –0,26, p <0.01 and r = 0,7 p <0.01, respectively, after treatment with r = –0,14, p <0.01 and r = 0,64, p <0.01, respectively. Conclusions. Intravitreal injection of angiogenesis inhibitor ranibizumab to patients with comorbidity fundus DR and AMD on a background of

  17. Role of type 1 and type 3 fimbriae in Klebsiella pneumoniae biofilm formation

    DEFF Research Database (Denmark)

    Schroll, C.; Barken, Kim Bundvig; Krogfelt, K.A.

    2010-01-01

    nosocomial infections. Most clinical K. pneumoniae isolates express two types of fimbrial adhesins, type 1 fimbriae and type 3 fimbriae. In this study, we characterized the role of type 1 and type 3 fimbriae in K. pneumoniae biofilm formation. Results: Isogenic fimbriae mutants of the clinical K. pneumoniae...... of planktonic cells. Type 1 fimbriae did not influence biofilm formation and the expression of type 1 fimbriae was found to be down-regulated in biofilm forming cells. In contrast, expression of type 3 fimbriae was found to strongly promote biofilm formation. Conclusion: By use of well defined isogenic mutants...... we found that type 3 fimbriae, but not type 1 fimbriae, strongly promote biofilm formation in K. pneumoniae C3091. As the vast majority of clinical K. pneumoniae isolates express type 3 fimbriae, this fimbrial adhesin may play a significant role in development of catheter associated K. pneumoniae...

  18. Theoretical models for Type I and Type II supernova

    International Nuclear Information System (INIS)

    Woosley, S.E.; Weaver, T.A.

    1985-01-01

    Recent theoretical progress in understanding the origin and nature of Type I and Type II supernovae is discussed. New Type II presupernova models characterized by a variety of iron core masses at the time of collapse are presented and the sensitivity to the reaction rate 12 C(α,γ) 16 O explained. Stars heavier than about 20 M/sub solar/ must explode by a ''delayed'' mechanism not directly related to the hydrodynamical core bounce and a subset is likely to leave black hole remnants. The isotopic nucleosynthesis expected from these massive stellar explosions is in striking agreement with the sun. Type I supernovae result when an accreting white dwarf undergoes a thermonuclear explosion. The critical role of the velocity of the deflagration front in determining the light curve, spectrum, and, especially, isotopic nucleosynthesis in these models is explored. 76 refs., 8 figs

  19. Object-Oriented Type Systems

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Palsberg, Jens

    a type system that generalizes and explains them. The theory is based on an idealized object-oriented language called BOPL (Basic Object Programming Language), containing common features of the above languages. A type system, type inference algorithm, and typings of inheritance and genericity......Object-Oriented Type Systems Jens Palsberg and Michael I. Schwartzbach Aarhus University, Denmark Type systems are required to ensure reliability and efficiency of software. For object-oriented languages, typing is an especially challenging problem because of inheritance, assignment, and late...... are provided for BOPL. Throughout, the results are related to the languages on which BOPL is based. This text offers advanced undergraduates and professional software developers a sound understanding of the key aspects of object-oriented type systems. All algorithms are implemented in a freely available...

  20. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    International Nuclear Information System (INIS)

    Piai, Juliana Francis; Alves da Silva, Marta; Martins, Albino; Torres, Ana Bela; Faria, Susana

    2017-01-01

    Highlights: • Chemical immobilization of chondroitin sulfate at the surface of nanofiber meshes. • CS-immobilized NFMs showed lower roughness and higher hydrophilicity. • CS-immobilized NFMs offer a highly effective substrate for hACs phenotypic stability. - Abstract: Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O_3 exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  1. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    Energy Technology Data Exchange (ETDEWEB)

    Piai, Juliana Francis [3B’s Research Group − Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães (Portugal); ICVS/3B’s − PT Government Associate Laboratory, Braga/Guimarães (Portugal); Grupo de Materiais Poliméricos e Compósitos, GMPC – Departamento de Química- Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900, Maringá, Paraná (Brazil); Alves da Silva, Marta; Martins, Albino; Torres, Ana Bela [3B’s Research Group − Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães (Portugal); ICVS/3B’s − PT Government Associate Laboratory, Braga/Guimarães (Portugal); Faria, Susana [Research Center Officinal Mathematical, Department of Mathematics for Science and Technology, University of Minho, Campus de Azurém, 4800-058 Guimarães (Portugal); and others

    2017-05-01

    Highlights: • Chemical immobilization of chondroitin sulfate at the surface of nanofiber meshes. • CS-immobilized NFMs showed lower roughness and higher hydrophilicity. • CS-immobilized NFMs offer a highly effective substrate for hACs phenotypic stability. - Abstract: Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O{sub 3} exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  2. Characterization of human adipose-derived stem cells and expression of chondrogenic genes during induction of cartilage differentiation

    Directory of Open Access Journals (Sweden)

    Adila A Hamid

    2012-01-01

    Full Text Available OBJECTIVES: Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction. MATERIALS AND METHODS: Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction. RESULTS: Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction. CONCLUSION: Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adiposederived stem cells was most prominent after one week of chondrogenic induction.

  3. Morphometric analysis of three normal facial types in mixed dentition using posteroanterior cephalometric radiographs: preliminary results

    Directory of Open Access Journals (Sweden)

    Renato Bigliazzi

    2017-08-01

    Full Text Available The aim of the present investigation was to evaluate the craniofacial features of subjects with normal occlusion with different vertical patterns in the mixed dentition using morphometric analysis (Thin-Plate Spline analysis - TPS applied to posteroanterior (PA films. The sample comprised 39 individuals (18 females and 21 males, all in mixed dentition, aged from 8.4 to 10 years with satisfactory occlusion and balanced profile and with no history of orthodontic or facial orthopedic treatment. The sample was divided into three groups (mesofacial, brachyfacial and dolichofacial according to the facial types proposed by Ricketts (1989. The average craniofacial configurations of each study group were obtained by orthogonal superimposition of Procrustes, thereby eliminating size differences and allowing only shape differences between groups to be analyzed by viewing the TPS deformation grid. Significant differences were found among the three facial types but were more remarkable between mesofacials and dolichofacials than between mesofacials and brachyfacials. TPS morphometric analysis proved efficient for accurate visualization of transverse and vertical differences among facial types even before pubertal growth spurt. These differences cannot be easily detected by traditional posteroanterior cephalometry.

  4. Hand functions in type 1 and type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Akpinar Pinar

    2017-01-01

    Full Text Available Introduction/Objective. Hand functions have an enormous impact on activities of daily living in patients with diabetes mellitus (DM, such as self-care, administering insulin injections, and preparing and eating meals. The aim of the study was to evaluate hand functions and grip strength in patients with type 1 and type 2 DM. Methods. This was an observational case-control study investigating the hand functions and grip strength in patients with type 1 and type 2 DM. The study comprised 41 patients with type 1 DM aged 25–50 years sex- and age-matched, 40 non-diabetic controls, and 91 patients with type 2 DM aged 40–65 years sex- and age-matched 60 non-diabetic controls. Patients with documented history of diabetic sensorimotor neuropathy and adhesive capsulitis were excluded. The Duruoz Hand Index was used to assess the functional hand disability. Grip strength was tested with a calibrated Jamar dynamometer. Results. The Duruoz Hand Index scores in patients with type 2 DM were significantly higher than in persons in the control group (p 0.05. Grip strength values of patients with type 1 DM were significantly lower compared to those in the control group (p < 0.05, whereas there was no significant difference between patients with type 2 DM and their control group. There was a negatively significant correlation between grip strength and the Duruoz Hand Index scores in patients with both type 1 and type 2 DM (p < 0.05. Conclusion. Patients with type 1 DM and type 2 DM have different degrees of hand disability as compared to healthy control groups.

  5. Sulphated glycosaminoglycans and proteoglycans in the developing vertebral column of juvenile Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Hannesson, Kirsten O; Ytteborg, Elisabeth; Takle, Harald; Enersen, Grethe; Bæverfjord, Grete; Pedersen, Mona E

    2015-08-01

    In the present study, the distribution of sulphated glycosaminoglycans (GAGs) in the developing vertebral column of Atlantic salmon (Salmo salar) at 700, 900, 1100 and 1400 d° was examined by light microscopy. The mineralization pattern was outlined by Alizarin red S and soft structures by Alcian blue. The temporal and spatial distribution patterns of different types of GAGs: chondroitin-4-sulphate/dermatan sulphate, chondroitin-6-sulphate, chondroitin-0-sulphate and keratan sulphate were addressed by immunohistochemistry using monoclonal antibodies against the different GAGs. The specific pattern obtained with the different antibodies suggests a unique role of the different GAG types in pattern formation and mineralization. In addition, the distribution of the different GAG types in normal and malformed vertebral columns from 15 g salmon was compared. A changed expression pattern of GAGs was found in the malformed vertebrae, indicating the involvement of these molecules during the pathogenesis. The molecular size of proteoglycans (PGs) in the vertebrae carrying GAGs was analysed with western blotting, and mRNA transcription of the PGs aggrecan, decorin, biglycan, fibromodulin and lumican by real-time qPCR. Our study reveals the importance of GAGs in development of vertebral column also in Atlantic salmon and indicates that a more comprehensive approach is necessary to completely understand the processes involved.

  6. The Role of an Aggrecan 32mer Fragment in Post-Traumatic Osteoarthritis

    Science.gov (United States)

    2017-10-01

    streptavidin-coated AlphaLISA donor beads and incubate for 30 minutes.  Read sample absorbance at 615nm on the PerkinElmer Enspire plate reader. 11...HRPO approval within the next six months. Nothing to report 15 Significant changes in use or care of human subjects, vertebrate animals ...human subjects, vertebrate animals , biohazards, and/or select agents during the reporting period. If required, were these changes approved by the

  7. The Preoperative Level of B-Type Natriuretic Peptides and the Results of Clinical and Functional Studies of Cardiosurgical Patients

    Directory of Open Access Journals (Sweden)

    I. A. Kozlov

    2009-01-01

    Full Text Available Objective: to study the plasma content of B-type natriuretic peptides in coronary heart disease patients prepared for surgery under extracorporeal circulation and to assess the association of the level of these biomarkers with the data of clinical and functional studies. Material and methods. The levels of active B-type natriuretic peptide were determined by immunofluoresence assay in the blood of 52 patients aged 57.8±1 years. The patients’ baseline clinical condition was in New York Heart Association (NYHA Functional Class I—IV. The left ventricular ejection fraction was 59.6±1.2%. The plasma concentration of the inactive N-terminal fragment of the BNP prohormone (NT-proBNP was estimated by electric chemiluminescence technique in 61 patients aged 54.6±1.18 years. The patients’ clinical condition was in NYHA Functional Class II—IV. The left ventricular ejection fraction was 51.5±1.6%. Results. The plasma content of B-type natriuretic peptide in the examinees was 48.5±5.9 pg/ml. The level of the biomarker correlated with the NYHA functional class (r=0.4; p=0.005, the electrocardiographic signs of postinfarct cardiosclerosis (r=0.29; p=0.04, and left ventricular ejection fraction (r=-0.41; p=0.003, and end-systolic volume (r=0.32; p=0.03. The plasma concentration of inactive NT-proBNP was 659.4±91.6 pg/ml. The level of the biomarker correlated with the NYHA functional class (r=0.4; p=0.002, the stage of circulatory insufficiency as described by I. D. Strazhesko and V. Kh. Vasilenko (r=0.49; p=0.001, and left ventricular ejection fraction (r=-0.45; p=0.001, and end-diastolic (r=0.39; p=0.002 and end-systolic (r=0.42; p=0.001 volumes. In patients with the values of the biomarker of less than 1000 pg/ml, the latter was related to age (r=0.3; p=0.047. Conclusion. The study of the level of B-type natriuretic peptides in cardiosurgical patients with coronary heart disease, prepared for surgery under extracorporeal circulation, suggests

  8. Occult CSF flow disturbance of patients with Alzheimer type dementia and vascular dementia; Results from Iotrolan CT-cisternography

    Energy Technology Data Exchange (ETDEWEB)

    Kono, Kazuhiko; Sugita, Yasuko; Funaki, Chiaki [Nagoya Univ. (Japan). Faculty of Medicine; and others

    1994-04-01

    We report results of Iotrolan CT-cisternography on 41 demented patients (13 males and 28 females) to find 'occult normal pressure hydrocephalus'. These patients were suspected to have CSF flow disturbance from clinical symptoms and simple brain CT scan findings. Their average age, duration of dementia, and score of Hasegawa's dementia scale (HDS) were 76.2 years, 5.9 years, 9.5/32.5,respectively. Before performing CT-cisternography, clinical diagnosis for their dementia were vascular dementia in 18 patients. Alzheimer type dementia in 12, suspect of NPH in 5, and other diagnoses in 6. From the results of cisternography, we found 13 patients with CSF flow disturbance (contrast material remained in the ventricle more than 48 hours after injection), and 17 patients with normal CSF flow. The former showed lower scores of HDS, higher urinary incontinence scores and smaller areas of the interhemispheric fissure on CT scan than the latter. But the former showed no significant difference from the latter in the average age, duration of dementia and width of the ventricles. (author).

  9. Analysis of simulation results of damaged nuclear fuel accidents at NPPs with shell-type nuclear reactors

    Directory of Open Access Journals (Sweden)

    Igor L. Kozlov

    2015-03-01

    Full Text Available Lessons from the accident at the Fukushima Daiichi NPP made it necessary to reevaluate and intensificate the work on modeling and analyzing various scenarios of severe accidents with damage to the nuclear fuel in the reactor, containment and spent nuclear fuel storage pool with the expansion of the primary initiating event causes group listing. Further development of computational tools for modeling the explosion prevention criteria as to steam and gas mixtures, considering the specific thermal-hydrodynamic conditions and mechanisms of explosive situations arrival at different stages of a severe accident development, is substantiated. Based on the analysis of the known shell-type nuclear reactors accidents results the explosion safety thermodynamic criteria are presented, the parameters defining the steam and gas explosions conditions are found, the need to perform the further verification and validation of deterministic codes serving to simulate general accident processes behavior as well as phase-to-phase interaction calculated dependencies is established. The main parameters controlling and defining the criteria explosion safety effective regulation areas and their optimization conditions are found.

  10. Identification of histological patterns in clinically affected and unaffected palm regions in dupuytren's disease.

    Directory of Open Access Journals (Sweden)

    Camilo-Andrés Alfonso-Rodríguez

    Full Text Available Dupuytren's disease is a fibro-proliferative disease characterized by a disorder of the extracellular matrix (ECM and high myofibroblast proliferation. However, studies failed to determine if the whole palm fascia is affected by the disease. The objective of this study was to analyze several components of the extracellular matrix of three types of tissues-Dupuytren's diseased contracture cords (DDC, palmar fascia clinically unaffected by Dupuytren's disease contracture (NPF, and normal forehand fascia (NFF. Histological analysis, quantification of cells recultured from each type of tissue, mRNA microarrays and immunohistochemistry for smooth muscle actin (SMA, fibrillar ECM components and non-fibrillar ECM components were carried out. The results showed that DDC samples had abundant fibrosis with reticular fibers and few elastic fibers, high cell proliferation and myofibroblasts, laminin and glycoproteins, whereas NFF did not show any of these findings. Interestingly, NPF tissues had more cells showing myofibroblasts differentiation and more collagen and reticular fibers, laminin and glycoproteins than NFF, although at lower level than DDC, with similar elastic fibers than DDC. Immunohistochemical expression of decorin was high in DDC, whereas versican was highly expressed NFF, with no differences for aggrecan. Cluster analysis revealed that the global expression profile of NPF was very similar to DDC, and reculturing methods showed that cells corresponding to DDC tissues proliferated more actively than NPF, and NPF more actively than NFF. All these results suggest that NPF tissues may be affected, and that a modification of the therapeutic approach used for the treatment of Dupuytren's disease should be considered.

  11. Identifying Barriers to Appropriate Use of Metabolic/Bariatric Surgery for Type 2 Diabetes Treatment: Policy Lab Results

    Science.gov (United States)

    Rubin, Jennifer K.; Hesketh, Rachel; Martin, Adam; Herman, William H.; Rubino, Francesco

    2016-01-01

    Despite increasing recognition of the efficacy, safety, and cost-effectiveness of bariatric/metabolic surgery in the treatment of type 2 diabetes, few patients who may be appropriate candidates and may benefit from this type of surgery avail themselves of this treatment option. To identify conceptual and practical barriers to appropriate use of surgical procedures, a Policy Lab was hosted at the 3rd World Congress on Interventional Therapies for Type 2 Diabetes on 29 September 2015. Twenty-six stakeholders participated in the Policy Lab, including academics, clinicians, policy-makers, industry leaders, and patient representatives. Participants were provided with a summary of available evidence about the cost-effectiveness of bariatric/metabolic surgery and the costs of increasing the use of bariatric/metabolic surgery, using U.K. and U.S. scenarios as examples of distinct health care systems. There was widespread agreement among this group of stakeholders that bariatric/metabolic surgery is a legitimate and cost-effective approach to the treatment of type 2 diabetes in obese patients. The following four building blocks were identified to facilitate policy changes: 1) communicating the scale of the costs and harms associated with rising prevalence of type 2 diabetes; 2) properly articulating the role of bariatric/metabolic surgery for certain population groups; 3) identifying new funding sources for bariatric/metabolic surgery; and 4) incorporating bariatric/metabolic surgery into the appropriate clinical pathways. Although more research is needed to identify specific clinical scenarios for the prioritization of bariatric/metabolic surgery, the case appears to be strong enough to engage relevant policy-makers and practitioners in a concerted discussion of how to better use metabolic surgical resources in conjunction with other interventions in good diabetes practice. PMID:27222554

  12. The results of correction of endothelial dysfunction in type 2 diabetes mellitus in patients with diabetic retinopathy and associated hypertension

    Directory of Open Access Journals (Sweden)

    L. K. Moshetova

    2013-01-01

    Full Text Available Purpose:Studying the dynamics of clinical functional and morphological status of the retina against the metabolic and antiischemic therapy of retinopathy in type 2 diabetes associated with hypertension based on indicators in the tear fluid and serum nitric oxide metabolites.Methods: Following a standard ophthalmologic examination of 50 patients, among which are the two groups are similar in age andsex. The main group (n = 37 with Cd 2, DR and DR I and II hypertension II, III stage, the average age was 62,2±1,2 years, antihypertensive therapy — an ACE inhibitor Prestarium (5 mg. Patients of the group were divided into two subgroups: the first subgroup (n = 19who underwent parabulbarnom Mildronate (10 injections, the second subgroup (n = 18, which the drug was administered intranasally Semaks (20 days. The control group (n = 13 healthy (n = 6, and patients with type 2 diabetes without DR and GB (n = 7. Quantitative determination of the stable NO metabolites was determined in biochemical method samples of serum and lacrimal fluid.Results: After completing a course of therapy for patients of the first subgroup marked decrease in retinal thickness (p ≤ 0,05 in f.centralis, temporal lobe, the upper and lower bands parafovea and temporal area perifovea, while in the second group — in 9 areas of the macular area (p ≤ 0.05. It is also noted a significant increase in sensitivity to light in the macular area in patients of both subgroups (MAIA. On the background of the treatment observed reduction of NOx in the lacrimal fluid and serum of patients in both clinical groups. Thus, reduction of NOx in the lacrimal fluid was statistically significant in the subgroup of patients receiving anti-ischemic therapy semaks (p <0,05. In both clinical subgroups after treatment revealed correlation between systolic blood pressure and the level of NOx in the serum (r = 0,4; p <0,05.Conclusion: The positive effect (p <0,05 antioxidant (Mildronat and

  13. Making Type Inference Practical

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Oxhøj, Nicholas; Palsberg, Jens

    1992-01-01

    We present the implementation of a type inference algorithm for untyped object-oriented programs with inheritance, assignments, and late binding. The algorithm significantly improves our previous one, presented at OOPSLA'91, since it can handle collection classes, such as List, in a useful way. Abo......, the complexity has been dramatically improved, from exponential time to low polynomial time. The implementation uses the techniques of incremental graph construction and constraint template instantiation to avoid representing intermediate results, doing superfluous work, and recomputing type information....... Experiments indicate that the implementation type checks as much as 100 lines pr. second. This results in a mature product, on which a number of tools can be based, for example a safety tool, an image compression tool, a code optimization tool, and an annotation tool. This may make type inference for object...

  14. Types of treatment collaboration between conventional and alternative practitioners-results from a research project at a Danish MS hospital.

    Science.gov (United States)

    Skovgaard, Lasse; Haahr, Niels; Bjerre, Liv; Launsø, Laila

    2010-12-23

    More than 50% of People with Multiple Sclerosis (PwMS) in Denmark use alternative treatment. Most of them combine alternative and conventional treatment, but PwMS often find that they engage in parallel courses of treatment between which there is no dialogue, coordination or synergy. For this reason the Danish Multiple Sclerosis Society conducted a research project to develop and examine different models for collaboration between conventional and alternative treatment providers. The empirical material consisted of 10 individual interviews with practitioners, a group interview with practitioners, a group interview with professional staff at the Danish Multiple Sclerosis hospital that provided the organisational framework for the project, interviews with 59 patients and written responses from participating treatment providers in connection with 29 practitioner-researcher seminars held during the period 2004-2010. Collaboration between researchers and the treatment team resulted in the development and examination of several models which describe the strengths and weaknesses of various types of collaboration. The models show that the various types of collaboration place different requirements on the degree of 1) mutual acknowledgement and understanding among practitioners and 2) flexibility and resources in the organizational framework. The analyses also point to the fact that the degree of patient activity must be considered in relation to a given type of collaboration. The relationship between integration and pluralism can contribute to a fruitful discussion in regards to the value of treatment collaboration. In addition to the many positive perspectives that characterise integration of different treatment modalities the project points to the importance of not overlooking the opportunities, values and potential inherent in a pluralistic ideal in the form of patients' own active efforts and the dynamism that can arise when the patient becomes a co-informant, co

  15. Generalized classification of welds according to defect type based on raidation testing results

    International Nuclear Information System (INIS)

    Adamenko, A.A.; Demidko, V.G.

    1980-01-01

    Constructed is a generalized classification of welds according to defect type, with respect to real danger of defect, which in the first approximation is proportional to relatively decrease of the thickness, and with respect to defect potential danger which can be determined by its pointing. According to this classification the welded joints are divided into five classes according to COMECON guides. The division into classes is carried out according to two-fold numerical criterium which is applicable in case of the presence of experimental data on three defect linear sizes. The above classification is of main importance while automatic data processing of the radiation testing

  16. 29 CFR 578.3 - What types of violations may result in a penalty being assessed?

    Science.gov (United States)

    2010-07-01

    ... assessed? 578.3 Section 578.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS MINIMUM WAGE AND OVERTIME VIOLATIONS-CIVIL MONEY PENALTIES § 578.3 What types... be assessed against any person who repeatedly or willfully violates section 6 (minimum wage) or...

  17. [Construction of injectable tissue engineered nucleus pulposus in vitro].

    Science.gov (United States)

    Tian, Huake; Wang, Jian; Chen, Chao; Liu, Jie; Zhou, Yue

    2009-02-01

    To investigate the feasibility of using thermo-sensitive chitosan hydrogen as a scaffold to construct tissue engineered injectable nucleus pulposus (NP). Three-month-old neonatal New Zealand rabbits (male or female) weighing 150-200 g were selected to isolate and culture NP cells. The thermo-sensitive chitosan hydrogel scaffold was made of chitosan, disodium beta-glycerophosphate and hydroxyethyl cellulose. Its physical properties and gross condition were observed. The tissue engineered NP was constructed by compounding the scaffold and rabbit NP cells. Then, the viability of NP cells in the chitosan hydrogel was observed 2 days after compound culture and the growth condition of NP cells on the scaffold was observed by SEM 7 days after compound culture. NP cells went through histology and immunohistochemistry detection and their secretion of aggrecan and expression of Col II mRNA were analyzed by RT-PCR 21 days after compound culture. The thermo-sensitive chitosan hydrogel was liquid at room temperature and solidified into gel at 37 degrees C (15 minutes) due to crosslinking reaction. Acridine orange-propidium iodide staining showed that the viability rate of NP cells in chitosan hydrogel was above 90%. Scanning electron microscope observation demonstrated that the NP cells were distributed in the reticulate scaffold, with ECM on their surfaces. The results of HE, toluidine blue, safranin O and histology and immunohistochemistry staining confirmed that the NP cells in chitosan hydrogel were capable of producing ECM. RT-PCR results showed that the secretion of Col II and aggrecan mRNA in NP cells cultured three-dimensionally by chitosan hydrogen scaffold were 0.631 +/- 0.064 and 0.832 +/- 0.052, respectively, showing more strengths of producing matrix than that of monolayer culture (0.528 +/- 0.039, 0.773 +/- 0.046) with a significant difference (P compound culture, and may be a potential NP cells carrier for tissue engineered NP.

  18. Discriminating the reaction types of plant type III polyketide synthases.

    Science.gov (United States)

    Shimizu, Yugo; Ogata, Hiroyuki; Goto, Susumu

    2017-07-01

    Functional prediction of paralogs is challenging in bioinformatics because of rapid functional diversification after gene duplication events combined with parallel acquisitions of similar functions by different paralogs. Plant type III polyketide synthases (PKSs), producing various secondary metabolites, represent a paralogous family that has undergone gene duplication and functional alteration. Currently, there is no computational method available for the functional prediction of type III PKSs. We developed a plant type III PKS reaction predictor, pPAP, based on the recently proposed classification of type III PKSs. pPAP combines two kinds of similarity measures: one calculated by profile hidden Markov models (pHMMs) built from functionally and structurally important partial sequence regions, and the other based on mutual information between residue positions. pPAP targets PKSs acting on ring-type starter substrates, and classifies their functions into four reaction types. The pHMM approach discriminated two reaction types with high accuracy (97.5%, 39/40), but its accuracy decreased when discriminating three reaction types (87.8%, 43/49). When combined with a correlation-based approach, all 49 PKSs were correctly discriminated, and pPAP was still highly accurate (91.4%, 64/70) even after adding other reaction types. These results suggest pPAP, which is based on linear discriminant analyses of similarity measures, is effective for plant type III PKS function prediction. pPAP is freely available at ftp://ftp.genome.jp/pub/tools/ppap/. goto@kuicr.kyoto-u.ac.jp. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  19. Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

    Science.gov (United States)

    Warzecha, Jörg; Göttig, Stephan; Brüning, Christian; Lindhorst, Elmar; Arabmothlagh, Mohammad; Kurth, Andreas

    2006-10-01

    Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed. MSCs when treated with either Shh or TGF-beta(1) showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.

  20. Status, results and usefulness of risk analyses for HTGR type reactors of different capacity accessory to planning

    International Nuclear Information System (INIS)

    Kroeger, W.; Mertens, J.

    1985-01-01

    As regards system-inherent risks, HTGR type reactors are evaluated with reference to the established light-water-moderated reactor types. Probabilistic HTGR risk analyses have shown modern HTGR systems to possess a balanced safety concept with a risk remaining distinctly below legally accepted values. Inversely, the development and optimization of the safety concepts have been (and are being) essentially co-determined by the probabilistic analyses, as it is technically sensible and economically necessary to render the specific safety-related HTGR properties eligible for licensing. (orig./HP) [de

  1. Chemical-free n-type and p-type multilayer-graphene transistors

    Energy Technology Data Exchange (ETDEWEB)

    Dissanayake, D. M. N. M., E-mail: nandithad@voxtel-inc.com [Voxtel Inc, Lockey Laboratories, University of Oregon, Eugene Oregon 97402 (United States); Eisaman, M. D. [Sustainable Energy Technologies Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Department of Electrical and Computer Engineering, Stony Brook University, Stony Brook, New York 11794 (United States); Department of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794 (United States)

    2016-08-01

    A single-step doping method to fabricate n- and p-type multilayer graphene (MG) top-gate field effect transistors (GFETs) is demonstrated. The transistors are fabricated on soda-lime glass substrates, with the n-type doping of MG caused by the sodium in the substrate without the addition of external chemicals. Placing a hydrogen silsesquioxane (HSQ) barrier layer between the MG and the substrate blocks the n-doping, resulting in p-type doping of the MG above regions patterned with HSQ. The HSQ is deposited in a single fabrication step using electron beam lithography, allowing the patterning of arbitrary sub-micron spatial patterns of n- and p-type doping. When a MG channel is deposited partially on the barrier and partially on the glass substrate, a p-type and n-type doping profile is created, which is used for fabricating complementary transistors pairs. Unlike chemically doped GFETs in which the external dopants are typically introduced from the top, these substrate doped GFETs allow for a top gate which gives a stronger electrostatic coupling to the channel, reducing the operating gate bias. Overall, this method enables scalable fabrication of n- and p-type complementary top-gated GFETs with high spatial resolution for graphene microelectronic applications.

  2. Mock-up test results of monoblock-type CFC divertor armor for JT-60SA

    Energy Technology Data Exchange (ETDEWEB)

    Higashijima, S. [Japan Atomic Energy Agency, 801-1 Mukoyama, Naka, Ibaraki 311-0193 (Japan)], E-mail: higashijima.satoru@jaea.go.jp; Sakurai, S.; Suzuki, S.; Yokoyama, K.; Kashiwa, Y.; Masaki, K.; Shibama, Y.K.; Takechi, M.; Shibanuma, K.; Sakasai, A.; Matsukawa, M.; Kikuchi, M. [Japan Atomic Energy Agency, 801-1 Mukoyama, Naka, Ibaraki 311-0193 (Japan)

    2009-06-15

    The JT-60 Super Advanced (JT-60SA) tokamak project starts under both the Japanese domestic program and the international program 'Broader Approach'. The maximum heat flux to JT-60SA divertor is estimated to {approx}15 MW/m{sup 2} for 100 s. Japan Atomic Energy Agency (JAEA) has developed a divertor armor facing high heat flux in the engineering R and D for ITER, and it is concluded that monoblock-type CFC divertor armor is promising for JT-60SA. The JT-60SA armor consists of CFC monoblocks, a cooling CuCrZr screw-tube, and a thin oxygen-free high conductivity copper (OFHC-Cu) buffer layer between the CFC monoblock and the screw-tube. CFC/OFHC-Cu and OFHC-Cu/CuCrZr joints are essential for the armor, and these interfaces are brazed. Needed improvements from ITER engineering R and D are good CFC/OFHC-Cu and OFHC-Cu/CuCrZr interfaces and suppression of CFC cracking. For these purposes, metalization inside CFC monoblock is applied, and we confirmed again that the mock-up has heat removal capability in excess of ITER requirement. For optimization of the fabrication method and understanding of the production yield, the mock-ups corresponding to quantity produced in one furnace at the same time is also produced, and the half of the mock-ups could remove 15 MW/m{sup 2} as required. This paper summarizes the recent progress of design and mock-up test results for JT-60SA divertor armor.

  3. Interspecies radioimmunoassay for the major structural proteins of primate type-D retroviruses

    International Nuclear Information System (INIS)

    Colcher, D.; Teramoto, Y.A.; Schlom, J.

    1977-01-01

    A competition radioimmunoassay has been developed in which type-D retroviruses from three primate species compete. The assay utilizes the major structural protein (36,000 daltons) of the endogenous squirrel monkey retrovirus and antisera directed against the major structural protein (27,000 daltons) of the Mason-Pfizer monkey virus isolated from rhesus monkeys. Purified preparations of both viruses grown in heterologous cells, as well as extracts of heterologous cells infected with squirrel monkey retrovirus or Mason-Pfizer monkey virus, compete completely in the assay. Addition of an endogenous virus of the langur monkey also results in complete blocking. No blocking in the assay is observed with type-C baboon viruses, woolly monkey virus, and gibbon virus. Various other type-C and type-B viruses also showed no reactivity. An interspecies assay has thus been developed that recognizes the type-D retroviruses from both Old World monkey (rhesus and langur) and New World monkey (squirrel) species

  4. Predictors of associated autoimmune diseases (AAID) in families with type 1 diabetes (T1D). Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

    Science.gov (United States)

    Wägner, Ana M; Santana, Ángelo; Hernández, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Didac

    2011-01-01

    Background Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAID) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAID in the Type 1 Diabetes Genetics Consortium (T1DGC) data set. Methods 3263 families with at least 2 siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD and anti-IA-2 were measured and HLA-genotyping was performed. Siblings with T1D with and without AAID were compared and a multivariate regression analysis was performed to find predictors of AAID. T1D-associated HLA haplotypes were defined as the 4 most susceptible and protective, respectively. Results AAID was present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, and there was a female predominance and more family history of AAID in the group with AAID, as well as more frequent anti-GAD and less frequent anti-IA2 positivity. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAID. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAID. Conclusions In patients with T1D, the presence of AAID is associated with female predominance, more frequent family history of AAID, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. PMID:21744463

  5. In Vivo Evaluation of Biocompatibility and Chondrogenic Potential of a Cell-Free Collagen-Based Scaffold

    Directory of Open Access Journals (Sweden)

    Giovanna Calabrese

    2017-11-01

    Full Text Available Injured articular cartilage has a limited innate regenerative capacity, due to the avascular nature and low cellularity of the tissue itself. Although several approaches have been proposed to repair the joint cartilage, none of them has proven to be effective. The absence of suitable therapeutic options has encouraged tissue-engineering approaches combining specific cell types and biomaterials. In the present work, we have evaluated the potential of a cell-free Collagen I-based scaffold to promote the augmentation of cartilage-like phenotype after subcutaneous implantation in the mouse. Forty female mice were grafted subcutaneously with scaffolds, while four additional mice without scaffold were used as negative controls. The effects of scaffold were evaluated at 1, 2, 4, 8, or 16 weeks after implantation. Immunohistochemical analysis shows the expression of typical cartilage markers, including type-II Collagen, Aggrecan, Matrilin-1 and Sox 9. These data are also confirmed by qRT-PCR that further show that both COL2A1 and COL1A1 increase over time, but the first one increases more rapidly, thus suggesting a typical cartilage-like address. Histological analysis shows the presence of some pericellular lacunae, after 8 and 16 weeks. Results suggest that this scaffold (i is biocompatible in vivo, (ii is able to recruit host cells (iii induce chondrogenic differentiation of host cells. Such evidences suggest that this cell-free scaffold is promising and represents a potential approach for cartilage regeneration.

  6. Potential Biomedical Application of Enzymatically Treated Alginate/Chitosan Hydrosols in Sponges—Biocompatible Scaffolds Inducing Chondrogenic Differentiation of Human Adipose Derived Multipotent Stromal Cells

    Directory of Open Access Journals (Sweden)

    Anna Zimoch-Korzycka

    2016-08-01

    Full Text Available Current regenerative strategies used for cartilage repair rely on biomaterial functionality as a scaffold for cells that may have potential in chondrogenic differentiation. The purpose of the research was to investigate the biocompatibility of enzymatically treated alginate/chitosan hydrosol sponges and their suitability to support chondrogenic differentiation of human adipose derived multipotent stromal cells (hASCs. The alginate/chitosan and enzyme/alginate/chitosan sponges were formed from hydrosols with various proportions and were used as a biomaterial in this study. Sponges were tested for porosity and wettability. The porosity of each sponge was higher than 80%. An equal dose of alginate and chitosan in the composition of sponges improved their swelling ability. It was found that equal concentrations of alginate and chitosan in hydrosols sponges assure high biocompatibility properties that may be further improved by enzymatic treatment. Importantly, the high biocompatibility of these biomaterials turned out to be crucial in the context of hydrosols’ pro-chondrogenic function. After exposure to the chondrogenic conditions, the hASCs in N/A/C and L/A/C sponges formed well developed nodules and revealed increased expression of collagen type II, aggrecan and decreased expression of collagen type I. Moreover, in these cultures, the reactive oxygen species level was lowered while superoxide dismutase activity increased. Based on the obtained results, we conclude that N/A/C and L/A/C sponges may have prospective application as hASCs carriers for cartilage repair.

  7. Interleukin-6 inhibits early differentiation of ATDC5 chondrogenic progenitor cells.

    Science.gov (United States)

    Nakajima, Shoko; Naruto, Takuya; Miyamae, Takako; Imagawa, Tomoyuki; Mori, Masaaki; Nishimaki, Shigeru; Yokota, Shumpei

    2009-08-01

    Interleukin (IL)-6 is a causative agent of systemic juvenile idiopathic arthritis (sJIA), a chronic inflammatory disease complicated with severe growth impairment. Recent trials of anti-IL-6 receptor monoclonal antibody, tocilizumab, indicated that tocilizumab blocks IL-6/IL-6 receptor-mediated inflammation, and induces catch-up growth in children with sJIA. This study evaluates the effects of IL-6 on chondrogenesis by ATDC5 cells, a clonal murine chondrogenic cell line that provides an excellent model for studying endochondral ossification at growth plate. ATDC5 cells were examined for the expression of IL-6 receptor and gp130 by fluorescence-activated cell sorting analysis. Recombinant murine IL-6 was added to ATDC5 cultures to observe cell differentiation, using a quantitative RT-PCR for the chondrogenic differentiation markers type II collagen, aggrecan, and type X collagen. To block IL-6, the anti-mouse IL-6 receptor monoclonal antibody MR16-1 was added. As a result, the cells expressed IL-6 receptor and gp130. The expression of chondrogenic differentiation marker gene was reduced by IL-6, but this was abrogated by MR16-1. We conclude that IL-6 inhibits early chondrogenesis of ATDC5 cells suggesting that IL-6 may affect committed stem cells at a cellular level during chondrogenic differentiation of growth plate chondrocytes, and that IL-6 may be a cellular-level factor in growth impairment in sJIA.

  8. Capital cost evaluation of liquid metal reactor by plant type - comparison of modular type with monolithic type -

    International Nuclear Information System (INIS)

    Mun, K. H.; Seok, S. D.; Song, K. D.; Kim, I. C.

    1999-01-01

    A preliminary economic comparison study was performed for KALIMER(Korea Advanced LIquid MEtal Reactor)between a modular plant type with 8 150MWe modules and a 1200MWe monolithic plant type. In both cases of FOAK (First-Of-A-Kind) Plant and NOAK (Nth-Of-A-Kind) Plant, the result says that the economics of monolithic plant is superior to its modular plant. In case of NOAK plant comparison, however, the cost difference is not significant. It means that modular plant can compete with monolithic plant in capital cost if it makes efforts of cost reduction and technical progress on the assumption that the same type of NOAK plant will be constructed continuously

  9. Early Results of the PETTICOAT Technique for the Management of Acute Type A Aortic Dissection.

    Science.gov (United States)

    Kotha, Vamshi Krishna; Pozeg, Zlatko I; Herget, Eric J; Moon, Michael C; Appoo, Jehangir J

    2017-08-01

    Conventional surgical techniques for acute Type A aortic dissection (ATAAD) generally fail to address residual dissection in the descending aorta. The persistence of a false lumen is associated with visceral malperfusion in the acute setting and adverse aortic remodeling in the chronic setting. Hybrid aortic arch repair techniques may improve perioperative and long-term mortality by expanding the true lumen and obliterating the false lumen. However, there is a limit to the extent of aortic coverage due to the concomitant risk of spinal cord ischemia. In Type B dissection, the PETTICOAT (Provisional Extension To Induce Complete Attachment) technique, which entails stent graft coverage of the primary intimal tear followed by bare metal stent placement distally, may improve true lumen caliber and promote false lumen thrombosis without increasing the risk of spinal cord ischemia, as intercostal branches remain perfused through the bare metal stents. The technique of hybrid arch with surgical creation of a Dacron landing zone covering a stent graft in the proximal descending aorta and bare metal stents in the thoraco-abdominal aorta is a promising concept in the treatment of ATAAD.

  10. Glimepiride versus pioglitazone combination therapy in subjects with type 2 diabetes inadequately controlled on metformin monotherapy: results of a randomized clinical trial.

    Science.gov (United States)

    Umpierrez, Guillermo; Issa, Maher; Vlajnic, Aleksandra

    2006-04-01

    To compare the effect of add-on glimepiride or pioglitazone in subjects with type 2 diabetes inadequately controlled on metformin monotherapy. Multicenter, randomized, parallel-group, open-label, forcedtitration study involving 203 adults with poorly controlled type 2 diabetes (A1C 7.5-10%) on metformin monotherapy. Subjects were randomized to receive glimepiride or pioglitazone, titrated to the maximum dose for 26 weeks. Subjects were evaluated for A1C changes, fasting plasma glucose (FPG), insulin, C-peptide, and lipid levels. Safety outcomes and diabetes-related healthcare resource utilization were also evaluated. Both treatment groups achieved similar and significant mean decreases from baseline to endpoint (week 26) in A1C (p = 0.0001) and FPG (p use of fasting C-peptide concentration > or = 0.27 nmol/L in the inclusion criteria was a potential limitation as it may have included those patients with an improved probability for glimepiride or pioglitazone response. In addition, a larger patient population would have provided a greater degree of data applicability. In patients with type 2 diabetes inadequately controlled on metformin monotherapy, add-on glimepiride or pioglitazone results in similar overall improvements in glycemic control. Compared with pioglitazone, glimepiride is associated with faster glycemic control, lower total and LDL cholesterol levels and reduced short-term healthcare costs.

  11. A study of HPV typing for the management of HPV-positive ASC-US cervical cytologic results.

    Science.gov (United States)

    Schiffman, Mark; Vaughan, Laurence M; Raine-Bennett, Tina R; Castle, Philip E; Katki, Hormuzd A; Gage, Julia C; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas

    2015-09-01

    In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with typing channel, using Kaplan-Meier methods. The 3-year CIN3+ risk for all HC2-positive women with ASC-US was 5.2%; this establishes the "benchmark" risk for colposcopic referral. Hierarchically, 3-year cumulative risks for each typing channel were 16.0% for HPV16, 7.4% for HPV18, 7.0% for HPV31, 7.1% for grouped HPV33/58, 4.3% for HPV52, 3.9% for HPV45, 2.7% for HPV51, 1.6% for HPV39/68/35, and 1.3% for HPV59/56/66. ASC-US linked to HPV16, HPV18, HPV31, or HPV33/58 warrants immediate colposcopy. Optimal management of women with HPV52 or HPV45 is uncertain. Risk of women with only HPV51, HPV39/68/35, or HPV59/56/66 might be low enough to recommend 1-year retesting permitting viral clearance. This strategy would defer colposcopy for 40% of women with HPV-positive ASC-US, half of whom would be cotest-negative at 1-year return. Approximately 10% of those with CIN3 diagnosable at enrollment would be delayed 1year instead. Cost-effectiveness analyses are needed. Published by Elsevier Inc.

  12. Effects of different computer typing speeds on acceleration and peak contact pressure of the fingertips during computer typing.

    Science.gov (United States)

    Yoo, Won-Gyu

    2015-01-01

    [Purpose] This study showed the effects of different computer typing speeds on acceleration and peak contact pressure of the fingertips during computer typing. [Subjects] Twenty-one male computer workers voluntarily consented to participate in this study. They consisted of 7 workers who could type 200-300 characteristics/minute, 7 workers who could type 300-400 characteristics/minute, and 7 workers who could type 400-500 chracteristics/minute. [Methods] This study was used to measure the acceleration and peak contact pressure of the fingertips for different typing speed groups using an accelerometer and CONFORMat system. [Results] The fingertip contact pressure was increased in the high typing speed group compared with the low and medium typing speed groups. The fingertip acceleration was increased in the high typing speed group compared with the low and medium typing speed groups. [Conclusion] The results of the present study indicate that a fast typing speed cause continuous pressure stress to be applied to the fingers, thereby creating pain in the fingers.

  13. Effects of two types of medical contrast media on routine chemistry results by three automated chemistry analyzers.

    Science.gov (United States)

    Park, Yu Jin; Rim, John Hoon; Yim, Jisook; Lee, Sang-Guk; Kim, Jeong-Ho

    2017-08-01

    The use of iodinated contrast media has grown in popularity in the past two decades, but relatively little attention has been paid to the possible interferential effects of contrast media on laboratory test results. Herein, we investigate medical contrast media interference with routine chemistry results obtained by three automated chemistry analyzers. Ten levels of pooled serum were used in the study. Two types of medical contrast media [Iopamiro (iopamidol) and Omnipaque (iohexol)] were evaluated. To evaluate the dose-dependent effects of the contrast media, iopamidol and iohexol were spiked separately into aliquots of serum for final concentrations of 1.8%, 3.6%, 5.5%, 7.3%, and 9.1%. The 28 analytes included in the routine chemistry panel were measured by using Hitachi 7600, AU5800, and Cobas c702 analyzers. We calculated the delta percentage difference (DPD) between the samples and the control, and examined dose-dependent trends. When the mean DPD values were compared with the reference cut-off criteria, the only uniformly interferential effect observed for all analyzers was in total protein with iopamidol. Two additional analytes that showed trends toward interferential effects only in few analyzers and exceeded the limits of the allowable error were the serum iron and the total CO 2 . The other combinations of analyzer and contrast showed no consistent dose-dependent propensity for change in any analyte level. Our study suggests that many of the analytes included in routine chemistry results, except total protein and serum iron, are not significantly affected by iopamidol and iohexol. These results suggest that it would be beneficial to apply a flexible medical evaluation process for patients requiring both laboratory tests and imaging studies, minimizing the need for strict regulations for sequential tests. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Evaluation of LABType® SSO HLA Typing using the Luminex Platform: Cord Blood Registry Typing for the Korean Population.

    Science.gov (United States)

    Roh, Eun-Youn; Song, Eun-Young; Chang, Jee-Young; Yoon, Jong-Hyun; Shin, Sue

    2016-08-01

    The performance of a new intermediate-resolution method using a PCR-Luminex platform and LABType® SSO A, B DRB1 kits as an HLA typing method for the cord blood (CB) registry of the Korean population was investigated. A total of 1,413 cord blood units (CBUs) were enrolled - 1,382 from Koreans and 31 from non-Koreans or mixed-ancestry individuals. HLA-A, -B, and -DRB1 typing was performed using the LABType® SSO typing kits. HLA typing with the DNA method and 2-digit results are mandatory for the public CB bank in Korea according to the "CB Act." The proportions of ambiguous results in the 2-digit assignment were 14.6% (206/1,413) and 14.8% (205/ 1,382) among the total subjects and the Korean donors, respectively. In the 2-digit resolution, 3 different HLA-A types (69 CBUs), 31 HLA-B types (124 CBUs), and 3 HLA-DRB1 types (13 CBUs) showed ambiguous results. The 'most probable type' to the ambiguous results based on the reported Korean HLA allele frequencies were able to be assigned. The most probable results were 100% consistent with the confirmed types as determined by the HD kits (DRB1) and additional PCR-SBT or PCR-SSP tests (A and B). Luminex technology is more automated and less labor intensive than the conventional SSO typing method, and the results are less affected by differences between inspectors. Although it is not satisfactory as a sole confirmation test and cannot be used as a replacement for the PCR-SBT test, the combination of Luminex technology with LABType® SSO kits and population frequency data provides a proper typing platform that can be used as a qualifying test for CB registries.

  15. Refinement Types for TypeScript

    OpenAIRE

    Vekris, Panagiotis; Cosman, Benjamin; Jhala, Ranjit

    2016-01-01

    We present Refined TypeScript (RSC), a lightweight refinement type system for TypeScript, that enables static verification of higher-order, imperative programs. We develop a formal core of RSC that delineates the interaction between refinement types and mutability. Next, we extend the core to account for the imperative and dynamic features of TypeScript. Finally, we evaluate RSC on a set of real world benchmarks, including parts of the Octane benchmarks, D3, Transducers, and the TypeScript co...

  16. Two thumbs and one index: A comparison of manual coordination in touch-typing and mobile-typing.

    Science.gov (United States)

    Cerni, Tania; Longcamp, Marieke; Job, Remo

    2016-06-01

    It has been extensively demonstrated that in touch-typing, manual alternation is performed faster than manual repetition (see i.e. Rumelhart & Norman, 1982), due to parallel activation of successive keystrokes. In this experiment, we tested whether the manual coordination patterns typical of touch-typing can be observed in mobile-typing. We recruited skilled touch-typists and divided them into two groups depending on their typing habits on the mobile device. The "one-hand" group typed with one index finger on the mobile, and therefore produced words exclusively through manual repetition. The "two-hands" group used two thumbs, and therefore produced words through a combination of mobile-typing repetitions and alternations. The two groups were tested in a typing to dictation task with both a standard keyboard and a mobile keyboard. Results showed that manual alternation and manual repetition patterns are similar in touch-typing and in mobile-typing. For the "two-hands" group, the mean interkeystroke intervals (IKIs) for touch-typing decreased as manual alterations in words increased in both touch- and mobile-typing. The "one-hand" group showed an opposite pattern in mobile-typing. Bigram frequency was correlated with IKIs per bigrams in both tasks and groups, but the correlation for the "one-hand" group in mobile-typing was different. Our results suggest that manual coordination processes are the same in touch-typing and in mobile-typing despite different effectors, provided that both hands are used to type. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Supplementary Material for: Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

    KAUST Repository

    Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

    2015-01-01

    Abstract Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis

  18. Parameters in pure type systems

    NARCIS (Netherlands)

    Bloo, C.J.; Kamareddine, F.; Laan, T.D.L.; Nederpelt, R.P.; Rajsbaum, S.

    2002-01-01

    In this paper we study the addition of parameters to typed ¿-calculus with definitions. We show that the resulting systems have nice properties and illustrate that parameters allow for a better fine-tuning of the strength of type systems as well as staying closer to type systems used in practice in

  19. Refining types using type guards in TypeScript

    NARCIS (Netherlands)

    de Wolff, Ivo Gabe; Hage, J.

    2017-01-01

    We discuss two adaptations of the implementation of type guards and narrowing in the TypeScript compiler. The first is an improvement on the original syntax-directed implementation, and has now replaced the original one in the TypeScript compiler. It is specifically suited for the scenario in which

  20. An investigation into the effect of type I and type II diabetes duration on employment and wages.

    Science.gov (United States)

    Minor, Travis

    2013-12-01

    Using data from the National Longitudinal Survey of Youth 1979, the current study examines the effect of type I and type II diabetes on employment status and wages. The results suggest that both the probability of employment and wages are negatively related to the number of years since the initial diagnosis of diabetes. Moreover, the effect of diabetes duration on the probability of employment appears to be nonlinear, peaking around 16 years for females and 10 years for males. A similar negative effect on wages is found only in male diabetics. Finally, the results suggest that failure to distinguish between type I and type II diabetics may lead to some counterintuitive results. Published by Elsevier B.V.

  1. Changes in expression of cartilaginous genes during chondrogenesis of Wharton's jelly mesenchymal stem cells on three-dimensional biodegradable poly(L-lactide-co-glycolide) scaffolds.

    Science.gov (United States)

    Paduszyński, Piotr; Aleksander-Konert, Ewelina; Zajdel, Alicja; Wilczok, Adam; Jelonek, Katarzyna; Witek, Andrzej; Dzierżewicz, Zofia

    2016-01-01

    In cartilage tissue regeneration, it is important to develop biodegradable scaffolds that provide a structural and logistic template for three-dimensional cultures of chondrocytes. In this study, we evaluated changes in expression of cartilaginous genes during in vitro chondrogenic differentiation of WJ-MSCs on PLGA scaffolds. The biocompatibility of the PLGA material was investigated using WJ-MSCs by direct and indirect contact methods according to the ISO 10993-5 standard. PLGA scaffolds were fabricated by the solvent casting/salt-leaching technique. We analyzed expression of chondrogenic genes of WJ-MSCs after a 21-day culture. The results showed the biocompatibility of PLGA and confirmed the usefulness of PLGA as material for fabrication of 3D scaffolds that can be applied for WJ-MSC culture. The in vitro penetration and colonization of the scaffolds by WJ-MSCs were assessed by confocal microscopy. The increase in cell number demonstrated that scaffolds made of PLGA copolymers enabled WJ-MSC proliferation. The obtained data showed that as a result of chondrogenesis of WJ-MSCs on the PLGA scaffold the expression of the key markers collagen type II and aggrecan was increased. The observed changes in transcriptional activity of cartilaginous genes suggest that the PLGA scaffolds may be applied for WJ-MSC differentiation. This primary study suggests that chondrogenic capacity of WJ-MSCs cultured on the PLGA scaffolds can be useful for cell therapy of cartilage.

  2. Chondrogenic potential of canine articular cartilage derived cells (cACCs

    Directory of Open Access Journals (Sweden)

    Nowak Urszula

    2016-01-01

    Full Text Available In the present paper, the potential of canine articular cartilage-derived cells (cACCs for chondrogenic differentiation was evaluated. The effectiveness of cACCs’ lineage commitment was analyzed after 14 days of culture in chondorgenic and non-chondrogenic conditions. Formation of proteoglycan-rich extracellular matrix was assessed using histochemical staining – Alcian Blue and Safranin-O, while elemental composition was determined by means of SEM-EDX. Additionally, ultrastructure of cACCs was evaluated using TEM. The expression of genes involved in chondrogenesis was monitored with quantitative Real Time PCR. Results obtained indicate that the potential of cACCs for cartilagous extracellular matrix formation may be maintained only in chondrogenic cultures. The formation of specific chondro-nodules was not observed in a non-chondrogenic culture environment. The analysis of cACCs’ ultrastructure, both in non-chondrogenic and chondrogenic cultures, revealed well-developed rough endoplasmatic reticulum and presence of mitochondria. The cACCs in chondrogenic medium shed an increased number of microvesicles. Furthermore, it was shown that the extracellular matrix of cACCs in chondrogenic cultures is rich in potassium and molybdenum. Additionally, it was determined that gene expression of collagen type II, aggrecan and SOX-9 was significantly increased during chondrogenic differentiation of cACCs. Results obtained indicate that the culture environment may significantly influence the cartilage phenotype of cACCs during long term culture.

  3. Type Classes for Lightweight Substructural Types

    Directory of Open Access Journals (Sweden)

    Edward Gan

    2015-02-01

    Full Text Available Linear and substructural types are powerful tools, but adding them to standard functional programming languages often means introducing extra annotations and typing machinery. We propose a lightweight substructural type system design that recasts the structural rules of weakening and contraction as type classes; we demonstrate this design in a prototype language, Clamp. Clamp supports polymorphic substructural types as well as an expressive system of mutable references. At the same time, it adds little additional overhead to a standard Damas-Hindley-Milner type system enriched with type classes. We have established type safety for the core model and implemented a type checker with type inference in Haskell.

  4. Type D personality, suboptimal health behaviors and emotional distress in adults with diabetes : Results from Diabetes MILES–The Netherlands

    NARCIS (Netherlands)

    Nefs, G.M.; Speight, J.; Pouwer, F.; Pop, V.J.M.; Bot, M.; Denollet, J.

    2015-01-01

    Aims Type D personality – defined as high negative affectivity (NA) and high social inhibition (SI) – has been associated with adverse cardiovascular prognosis. We explored the differential associations of Type D personality and its constituent components with health behaviors, emotional distress

  5. Healthcare resource use, direct and indirect costs of hypoglycemia in type 1 and type 2 diabetes, and nationwide projections. Results of the HYPOS-1 study.

    Science.gov (United States)

    Giorda, C B; Rossi, M C; Ozzello, O; Gentile, S; Aglialoro, A; Chiambretti, A; Baccetti, F; Gentile, F M; Romeo, F; Lucisano, G; Nicolucci, A

    2017-03-01

    To obtain an accurate picture of the total costs of hypoglycemia, including the indirect costs and comparing the differences between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). HYPOS-1 was a multicenter, retrospective cohort study which analyzed the data of 2229 consecutive patients seen at 18 diabetes clinics. Data on healthcare resource use and indirect costs by diabetes type were collected via a questionnaire. The domains of inpatient admission and hospital stay, work days lost, and third-party assistance were also explored. Resource utilization was reported as estimated incidence rates (IRs) of hypoglycemic episodes per 100 person-years and estimated costs as IRs per person-years. For every 100 patients with T1DM, 9 emergency room (ER) visits and 6 emergency medical service calls for hypoglycemia were required per year; for every 100 patients with T2DM, 3 ER visits and 1 inpatient admission were required, with over 3 nights spent in hospital. Hypoglycemia led to 58 work days per 100 person-years lost by the patient or a family member in T1DM versus 19 in T2DM. The costs in T1DM totaled €90.99 per person-year and €62.04 in T2DM. Direct and indirect costs making up the total differed by type of diabetes (60% indirect costs in T1DM versus 43% in T2DM). The total cost associated with hypoglycemia in Italy is estimated to be €107 million per year. Indirect costs meaningfully contribute to the total costs associated with hypoglycemia. As compared with T1DM, T2DM requires fewer ER visits and incurs lower indirect costs but more frequent hospital use. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  6. Personality types of entrepreneurs.

    Science.gov (United States)

    Müller, Günter F; Gappisch, Cathrin

    2005-06-01

    85 German entrepreneurs were psychometrically assessed on 12 primary trait characteristics. The sample consisted of 49 men and 36 women whose mean age was 45.6 yr. (SD= 10.3). Occupational domains were production (40%) and services (60%). The mean duration of entrepreneurship within these domains was 13.1 yr. (SD=9.3). By factor analysis five personality types of entrepreneurs could be identified: Creative Acquisitor, Controlled Perseverator, Distant Achiever, Rational Manager, and Egocentric Agitator. These types correspond with types found in research by Miner and with the Myer-Briggs Indicator. In addition, correlations between general type potential and both job and life satisfaction of entrepreneurs were found. The results are discussed with regard to intercultural stability of personality types and implications for research and application.

  7. Wild type measles virus attenuation independent of type I IFN

    Directory of Open Access Journals (Sweden)

    Horvat Branka

    2008-02-01

    Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

  8. Spontaneous complement activation on human B cells results in localized membrane depolarization and the clustering of complement receptor type 2 and C3 fragments

    DEFF Research Database (Denmark)

    Løbner, Morten; Leslie, Robert G Q; Prodinger, Wolfgang M

    2009-01-01

    While our previous studies have demonstrated that complement activation induced by complement receptors type 2 (CR2/CD21) and 1 (CR1/CD35) results in C3-fragment deposition and membrane attack complex (MAC) formation in human B cells, the consequences of these events for B-cell functions remain u...

  9. Early results of valve-sparing ascending aortic replacement in type A aortic dissection and aortic insufficiency

    Directory of Open Access Journals (Sweden)

    М. Л. Гордеев

    2016-08-01

    Full Text Available Aim: The study was designed to investigate predictors of effective valve-sparing ascending aortic replacement in patients with Stanford type A aortic dissection combined with aortic insufficiency and to analyze efficacy and safety of this kind of surgery.Methods: From January 2010 to December 2015, 49 patients with Stanford type A aortic dissection combined with aortic insufficiency underwent ascending aortic replacement. All patients were divided into 3 groups: valve-sparing procedures (group 1, n = 11, combined aortic valve and supracoronary ascending aortic replacement (group 2, n = 12, and Bentall procedure (group 3, n = 26. We assessed the initial status of patients, incidence of complications and efficacy of valve-sparing ascending aortic replacement.Results: The hospital mortality rate was 8.2% (4/49 patients. The amount of surgical correction correlated with the initial diameter of the aorta at the level of the sinuses of Valsalva. During the hospital period, none of patients from group 1 developed aortic insufficiency exceeding Grade 2 and the vast majority of patients had trivial aortic regurgitation. The parameters of cardiopulmonary bypass, cross-clamp time and circulatory arrest time did not correlate with the initial size of the ascending aorta and aortic valve blood flow impairment, neither did they influence significantly the incidence and severity of neurological complications. The baseline size of the ascending aorta and degree of aortic regurgitation did not impact the course of the early hospital period.Conclusions: Supracoronary ascending aortic replacement combined with aortic valve repair in ascending aortic dissection and aortic regurgitation is effective and safe. The initial size of the ascending aorta and aortic arch do not influence immediate results. The diameter of the aorta at the level of the sinuses of Valsalva and the condition of aortic valve leaflets could be considered as the limiting factors. Further long

  10. Types of treatment collaboration between conventional and alternative practitioners – results from a research project at a Danish MS hospital

    Directory of Open Access Journals (Sweden)

    Lasse Skovgaard

    2010-12-01

    Full Text Available Introduction: More than 50% of the People with Multiple Sclerosis (PwMS in Denmark use alternative treatment. Most of them combine alternative and conventional treatment, but PwMS often find that there is no dialogue, coordination or synergy between the parallel courses of treatment offered. For this reason the Danish Multiple Sclerosis Society conducted a research project to develop and examine different models for collaboration between conventional and alternative treatment providers. Materials and methods: Empirical material consist of individual interviews with practitioners, a group interview with practitioners, a group interview with professional staff at the Danish MS hospital that provided the organisational framework for the project, interviews with patients as well as written responses from participating treatment providers in connection with practitioner-researcher seminars held. Results: Collaboration between researchers and the treatment team resulted in the development examination of several models which describe the strengths and weaknesses of various types of collaboration. The models also show that the various types of collaboration place different requirements on the degree of 1 mutual acknowledgement and understanding among practitioners, 2 flexibility and resources in the organizational framework, and 3 patients' activities and own efforts, respectively.    Perspectives: The relationship between integration and pluralism can contribute to a fruitful discussion in regards to the value of treatment collaboration. In addition to the many positive perspectives the characterise integration of different treatment modalities the project points to the importance of not overlooking the opportunities, values and potential inherent in a pluralistic ideal in the form of patients' own active efforts and the dynamism that can arise when the patient becomes a co-informant, co-coordinator and/or co-integrator.

  11. Timanoplastia myringoplasty type 1 and in residency surgical results and audiometric

    Directory of Open Access Journals (Sweden)

    Buschle, Mauricio

    2010-12-01

    Full Text Available Introduction: The tympanoplasty aims to reconstruct the tympanic membrane, restoring protection to the middle ear and improve hearing. In this study we evaluated the surgical results and audiometric this surgery, performed in the service of Otorhinolaryngology, HC / UFPR by residents of the second year in the year 2008 and factors that may influence the results. Method: A retrospective study through review of medical records. Results: Among the 31 patients evaluated, there was closure of the perforation in 24 (80% and hearing improvement with reduction or closure of the conductive gap by 60% and 26.7% respectively. Discussion: The success rate of surgery was satisfactory and similar to that found in the literature, and factors such as age, presence of unilateral or bilateral pathology and size of perforation were not determinants of surgical success. Conclusion: Tympanoplasty performed by residents of the second year of residence showed satisfactory results regarding both surgical audiometric.

  12. The results of dosimetric type tests on the sample of LiF:Mg,Ti thermoluminescence dosimeters produced in Iran

    International Nuclear Information System (INIS)

    Jafarizadeh, M.; Hosseini Pooya, S. M.; Firoozi, B.; Kamali Shoroodani, A. R.; Mohammadi, Kh.

    2011-01-01

    In this investigation, the standard type tests performed on the LiF:Mg,Ti chip samples which have been produced in Iran. The dosimetry tests are consisting of sensitivity, homogeneity, linearity, reproducibility, minimum measurable dose, self and residual doses. The obtained results show that some of the tests such as sensitivity, minimum measurable dose, self and residual doses fulfill the criteria given by IEC 61066 and ASTM E668 standards; however, the remaining tests show some discrepancies in comparison with the standards. Also the sensitivity was measured to be 0.92 of that of commercially available TLD-100 (Harshaw) sample. So, the produced LiF:Mg,Ti dosimeter can be used in a routine personal/environmental and medical dosimetry with considering its precision.

  13. Types for DSP Assembler Programs

    DEFF Research Database (Denmark)

    Larsen, Ken

    2006-01-01

    for reuse, and a procedure that computes point-wise vector multiplication. The latter uses a common idiom of prefetching memory resulting in out-of-bounds reading from memory. I present two extensions to the baseline type system: The first extension is a simple modification of some type rules to allow out......-ofbounds reading from memory. The second extension is based on two major modifications of the baseline type system: • Abandoning the type-invariance principle of memory locations and using a variation of alias types instead. • Introducing aggregate types, making it possible to have different views of a block...... of memory, thus enabling type checking of programs that directly manage and reuse memory. I show that both the baseline type system and the extended type system can be used to give type annotations to handwritten DSP assembler code, and that these annotations precisely and succinctly describe...

  14. Self-Esteem of Rural Teens: Results for Three Family Types.

    Science.gov (United States)

    Hall, Anita M.; Rowe, George P.

    1991-01-01

    A total of 108 (of 200) adolescents completed the Coopersmith Self-Esteem Inventory and family characteristics questionnaire. Results showed that it is not the structure of the family but the degree of discord within the family that influences self-esteem. (Author/JOW)

  15. Effect of Dynamic Culture and Periodic Compression on Human Mesenchymal Stem Cell Proliferation and Chondrogenesis.

    Science.gov (United States)

    Guo, Ting; Yu, Li; Lim, Casey G; Goodley, Addison S; Xiao, Xuan; Placone, Jesse K; Ferlin, Kimberly M; Nguyen, Bao-Ngoc B; Hsieh, Adam H; Fisher, John P

    2016-07-01

    We have recently developed a bioreactor that can apply both shear and compressive forces to engineered tissues in dynamic culture. In our system, alginate hydrogel beads with encapsulated human mesenchymal stem cells (hMSCs) were cultured under different dynamic conditions while subjected to periodic, compressive force. A customized pressure sensor was developed to track the pressure fluctuations when shear forces and compressive forces were applied. Compared to static culture, dynamic culture can maintain a higher cell population throughout the study. With the application of only shear stress, qRT-PCR and immunohistochemistry revealed that hMSCs experienced less chondrogenic differentiation than the static group. The second study showed that chondrogenic differentiation was enhanced by additional mechanical compression. After 14 days, alcian blue staining showed more extracellular matrix formed in the compression group. The upregulation of the positive chondrogenic markers such as Sox 9, aggrecan, and type II collagen were demonstrated by qPCR. Our bioreactor provides a novel approach to apply mechanical forces to engineered cartilage. Results suggest that a combination of dynamic culture with proper mechanical stimulation may promote efficient progenitor cell expansion in vitro, thereby allowing the culture of clinically relevant articular chondrocytes for the treatment of articular cartilage defects.

  16. Devitalisation of human cartilage by high hydrostatic pressure treatment: Subsequent cultivation of chondrocytes and mesenchymal stem cells on the devitalised tissue

    Science.gov (United States)

    Hiemer, B.; Genz, B.; Jonitz-Heincke, A.; Pasold, J.; Wree, A.; Dommerich, S.; Bader, R.

    2016-01-01

    The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair. PMID:27671122

  17. Preliminary results of effect of environment on the low cycle fatigue behaviour of type 316 stainless steel and 9% Cr ferritic steel

    International Nuclear Information System (INIS)

    Wood, D.S.; Slattery, G.F.; Wynn, J.; Connaughton, M.D.; Lambert, M.E.

    1976-06-01

    Strain controlled fatigue tests on Type 316 steel at 625 0 C and 9% Cr steel at 525 0 C have been performed in air and in helium containing 200 μ atm H 2 and 1 μ atm H 2 O. In rapid cycling the endurance of Type 316 steel in this helium mixture was found to be about five times longer than in air. When a hold time was introduced into the tension part of the cycle however the endurance in the two environments was found to be virtually identical. Fractomicrographic examinations have been performed which have helped to explain some of these findings which are attributed to differences in oxidation behaviour at the crack tip. In the case of the 90% Cr steel the endurance in the helium mixture was found to be only slightly better than in air. The implications of these results are considered in relation to thermal shock effects on sodium cooled fast reactor components. (author)

  18. L1CAM in Early-Stage Type I Endometrial Cancer: Results of a Large Multicenter Evaluation

    NARCIS (Netherlands)

    Zeimet, A.G.; Reimer, D.; Huszar, M.; Winterhoff, B.; Puistola, U.; Azim, S.A.; Muller-Holzner, E.; Ben-Arie, A.; Kempen, L.C.L.T. van; Petru, E.; Jahn, S.; Geels, Y.P.; Massuger, L.F.A.G.; Amant, F.; Polterauer, S.; Lappi-Blanco, E.; Bulten, J.; Meuter, A.; Tanouye, S.; Oppelt, P.; Stroh-Weigert, M.; Reinthaller, A.; Mariani, A.; Hackl, W.; Netzer, M.; Schirmer, U.; Vergote, I.; Altevogt, P.; Marth, C.; Fogel, M.

    2013-01-01

    BACKGROUND: Despite the excellent prognosis of Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to

  19. The Type 3 copper site is intact but labile in Type 2-depleted laccase

    DEFF Research Database (Denmark)

    Frank, P; Farver, O; Pecht, I

    1983-01-01

    We report results of experiments designed to characterize the Type 1 and Type 3 copper sites in Rhus laccase depleted of Type 2 copper (T2D). Use of the Lowry method for determining protein concentration yielded the value 5620 +/- 570 M-1 cm-1 for the extinction of the 615-nm absorption band...... as intensity perturbations at 280 and 615 nm. Comparison of difference spectra show that this 330-nm band derives from a Type 3 copper-bound peroxide and not from a reoxidized Type 3 site. Dioxygen reoxidation of ascorbate-reduced T2D laccase produced new difference bands at 330 nm (delta epsilon = 770 M-1 cm...

  20. Evaluation of the HOOF-Print assay for typing Brucella abortus strains isolated from cattle in the United States: results with four performance criteria

    Directory of Open Access Journals (Sweden)

    Ewalt Darla R

    2005-06-01

    Full Text Available Abstract Background A fundamental question that arises during epidemiological investigations of bacterial disease outbreaks is whether the outbreak strain is genetically related to a proposed index strain. Highly discriminating genetic markers for characterizing bacterial strains can help in clarifying the genetic relationships among strains. Under the auspices of the European Society of Clinical Microbiology and Infectious Diseases, the European Study Group for Epidemiological Markers (ESGEM established guidelines for evaluating the performance of typing systems based of a number of criteria. Recently, HOOF-Print genotype analysis, a new method for typing Brucella abortus strains based on hypervariability at eight tandem repeat loci, was described. This paper evaluates the HOOF-Print assay by four of the criteria set out by the ESGEM: typeability, reproducibility, power of discrimination, and concordance with other typing methods. Results The HOOF-Print Assay was evaluated with a test population composed of 97 unrelated field isolates and 6 common laboratory strains of B. abortus. Both typeability and reproducibility of the assay were excellent. Allele diversity and frequency varied widely among the eight loci, ranging from 1 to 13 alleles. The power of discrimination, measured by the Hunter-Gaston discrimination index (HGDI, varied by locus ranging from 0 to 0.89, where a maximal value of 1.0 indicates discrimination of all strains. The HGDI values calculated for subgroups sorted by biovar were similar to the values determined for the whole population. None of the individual loci achieved the recommended HGDI threshold of 0.95, but the HGDI of the composite profiles was 0.99 (93 unique genotypes from 97 field strains evaluated, well above the recommended threshold. By comparison, the HGDI value for biovar typing was 0.61 in a test population biased with disproportionate numbers of the less common biovars. Cluster analysis based on HOOF

  1. Behavioral economics survey of patients with type 1 and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Emoto N

    2015-05-01

    Full Text Available Naoya Emoto,1 Fumitaka Okajima,1 Hitoshi Sugihara,2 Rei Goto3,4 1Division of Endocrinology, Department of Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, 2Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, 3Hakubi Center of Advanced Research, Kyoto University, Kyoto, 4Graduate School of Economics, Kyoto University, Kyoto, Japan Background: Adherence to treatment and the metabolic control of diabetes are challenging in many patients with diabetes. The theory of neuroeconomics can provide important clues for understanding unreasonable human behavior concerning decisions between outcomes occurring at different time points.  Objective: We investigated patients with type 1 and type 2 diabetes to determine whether patients who are at a risk of developing complications are less risk averse. We also examined whether patients with type 1 and type 2 diabetes have different behavioral traits in decision making under risk.  Methods: We conducted a behavioral economics survey of 219 outpatients, 66 with type 1 diabetes and 153 with type 2 diabetes. All patients had been referred by general practitioners or other departments in the hospital. At the time of the survey, levels of hemoglobin A1c were not significantly different between patients with type 1 and type 2 diabetes.  Results: Patients with type 2 diabetes showed a lower response rate to the survey compared with patients with type 1 diabetes (71.9% vs 87.9%, P<0.01. Logistic regression analysis indicated that diabetic retinopathy was negatively associated with risk averse in pricing of hypothetical lotteries, myopic time preference, willingness to pay for preventive medicine, and levels of satisfaction with life. Diabetic nephropathy was also negatively associated with risk averse in pricing of hypothetical lotteries. Detailed analysis revealed that a lower proportion of patients with type 2 diabetes (22.7% were categorized

  2. Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

    Science.gov (United States)

    Telander, R L; Zimmerman, D; van Heerden, J A; Sizemore, G W

    1986-12-01

    Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Psychological Type of Person-Centered Counselors.

    Science.gov (United States)

    Robbins, Mandy; Turley, Joanne

    2016-02-01

    There are various models and approaches to counseling and psychotherapy. Important characteristics of therapists include psychological type. This study aimed to investigate the psychological type profile of person-centered counselors. The psychological type of 85 counselors (63 women, 22 men) was measured with the Francis Psychological Type Scales (FPTS). Results indicate that the FPTS can reliably measure psychological type among counselors, and the most common psychological type was introvert, intuitive, feeling, and judging (INFJ). The relation of these psychological types with a person-centered approach is further discussed.

  4. The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results.

    Science.gov (United States)

    Mahon, Jeffrey L; Sosenko, Jay M; Rafkin-Mervis, Lisa; Krause-Steinrauf, Heidi; Lachin, John M; Thompson, Clinton; Bingley, Polly J; Bonifacio, Ezio; Palmer, Jerry P; Eisenbarth, George S; Wolfsdorf, Joseph; Skyler, Jay S

    2009-04-01

    TrialNet's goal to test preventions for type 1 diabetes has created an opportunity to gain new insights into the natural history of pre-type 1 diabetes. The TrialNet Natural History Study (NHS) will assess the predictive value of existing and novel risk markers for type 1 diabetes and will find subjects for prevention trials. The NHS is a three-phase, prospective cohort study. In phase 1 (screening), pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell antibodies) are measured. Phase 2 (baseline risk assessment) includes oral glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5-yr diabetes risks according to the OGTT and number of confirmed positive antibody tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6 months. In phases 2 and 3, samples are collected for future tests of T-lymphocyte function, autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome is diabetes onset. Of 12 636 relatives screened between March 2004 and December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of these, 322 were confirmed antibody positive and completed phase 2, of whom 296 subjects were given preliminary 5-yr diabetes risks of or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =50%). The NHS is identifying potential prevention trial subjects and is assembling a large cohort that will provide new natural history information about pre-type 1 diabetes. Follow-up to diabetes will help establish the biological significance and clinical value of novel type 1 diabetes risk markers.

  5. Abnormal levels of adipokines in adolescent offspring of women with type 1 diabetes - Results from the EPICOM study

    DEFF Research Database (Denmark)

    Lohse, Zuzana; Bytoft, Birgitte; Knorr, Sine

    2017-01-01

    AIMS/HYPOTHESIS: To investigate long-term consequences of diabetes during pregnancy, we determined adiponectin and leptin levels in adolescents born by women with type 1 diabetic (T1D) or non-diabetic mothers, and determined associations between adiponectin and leptin levels in adolescence...... and the magnitude of intrauterine hyperglycemia. RESEARCH DESIGN AND METHODS: We measured serum adiponectin and leptin and calculated leptin to adiponectin ratio (LAR) in 271 offspring of T1D women (index offspring) (13-20years), and 297 matched control offspring. Anthropometry included total body fat (TBF) by dual......-energy X-ray absorptiometry and an oral glucose tolerance test. RESULTS: Adiponectin levels were lower in index females (-8.0% (95% CI; -13.9, -1.6)), but not in index males (0.4% (95% CI; -7.3, 8.6)). Leptin levels were approximately 30% higher in index than control offspring, irrespective of gender...

  6. No evidence for increased self-reported cognitive failure in Type 1 and Type 2 diabetes

    DEFF Research Database (Denmark)

    Wessels, A M; Pouwer, F; Geelhoed-Duijvestijn, P H L M

    2007-01-01

    in adult out-patients with Type 1 and Type 2 diabetes. METHODS: Subjective cognitive functioning was measured in 187 diabetic patients using the Cognitive Failures Questionnaire (CFQ). Demographic and clinical characteristics were retrieved from the medical records. The Patient Health Questionnaire 9 items...... (PHQ-9) was self-administered along with the CFQ to correct for the confounding effect of depression. RESULTS: Analyses were based on 55 patients with Type 1 diabetes and 100 patients with Type 2 diabetes. No difference in mean CFQ score was observed between Type 1 and Type 2 diabetic patients...... or between Type 1 diabetic patients and healthy control subjects. Female patients with Type 2 diabetes reported significantly fewer cognitive complaints compared with female healthy control subjects. None of the demographic variables and diabetes-related complications was associated with subjective cognitive...

  7. Velocity-mass correlation of the O-type stars: model results

    International Nuclear Information System (INIS)

    Stone, R.C.

    1982-01-01

    This paper presents new model results describing the evolution of massive close binaries from their initial ZAMS to post-supernova stages. Unlike the previous conservative study by Stone [Astrophys. J. 232, 520 (1979) (Paper II)], these results allow explicitly for mass loss from the binary system occurring during the core hydrogen- and helium-burning stages of the primary binary star as well as during the Roche lobe overflow. Because of uncertainties in these rates, model results are given for several reasonable choices for these rates. All of the models consistently predict an increasing relation between the peculiar space velocities and masses for runaway OB stars which agrees well with the observed correlations discussed in Stone [Astron. J. 86, 544 (1981) (Paper III)] and also predict a lower limit at Mroughly-equal11M/sub sun/ for the masses of runaway stars, in agreement with the observational limit found by A. Blaauw (Bull. Astron. Inst. Neth. 15, 265, 1961), both of which support the binary-supernova scenario described by van den Heuvel and Heise for the origin of runaway stars. These models also predict that the more massive O stars will produce correspondingly more massive compact remnants, and that most binaries experiencing supernova-induced kick velocities of magnitude V/sub k/> or approx. =300 km s -1 will disrupt following the explosions. The best estimate for this velocity as established from pulsar observations is V/sub k/roughly-equal150 km s -1 , in which case probably only 15% if these binaries will be disrupted by the supernova explosions, and therefore, almost all runaway stars should have either neutron star or black hole companions

  8. Barriers towards insulin therapy in type 2 diabetic patients: results of an observational longitudinal study

    Directory of Open Access Journals (Sweden)

    Kulzer Bernd

    2010-10-01

    Full Text Available Abstract Background The course of barriers towards insulin therapy was analysed in three different groups of type 2 diabetic patients. This observational longitudinal study surveyed a three-month follow-up. Methods Participants in this study totalled 130 type 2 diabetic patients. The first subgroup was on insulin therapy at baseline (group 1: n = 57, age 55.6 ± 8.7 yrs, disease duration 12.7 ± 7.2 yrs, HbA1c 8.5 ± 1.6% and remained on insulin at follow-up. Of an initial 73 insulin-naïve patients, 44 were switched to insulin therapy (group 2: age 58.1 ± 6.8 yrs, disease duration 7.7 ± 5.0 yrs, HbA1c 9.1 ± 1.7% and 29 patients remained on an oral regimen (group 3: age 52.7 ± 10.7 yrs, disease duration 5.3 ± 4.6 yrs, HbA1c 8.3 ± 1.4%. Barriers towards insulin therapy were measured using the Insulin Treatment Appraisal Scale (ITAS. As generic instruments of health related quality of life patients completed also the Problem Areas of Diabetes Questionnaire (PAID, the WHO-5 Well-Being Scale (WHO-5, the Centre for Epidemiologic Studies Depression Scale (CES-D and the Trait Version of the State Trait Anxiety Inventory (STAI at baseline and at three-month follow-up. Results At the three-month follow-up, HbA1c had improved in all three groups (7.7 ± 1.2% vs. 7.1 ± 1.1% vs. 6.7 ± 0.8%. The course of negative appraisal of insulin therapy was significantly different in the three groups (p > .003: the ITAS score increased in patients remained on oral antidiabetic drugs (51.2 ± 12.2 to 53.6 ± 12.3, whereas it decreased in patients switched to insulin therapy (49.2 ± 9.8 to 46.2 ± 9.9 or remained on insulin treatment (45.8 ± 8.3 to 44.5 ± 8.0. Diabetes-related distress, trait anxiety, and well-being, showed a similar course in all three groups. The depression score improved significantly in patients switched to insulin treatment compared with patients remaining on insulin therapy. Conclusions In summary, this study suggests that a negative

  9. Weather types in the South Shetlands (Antarctica) using a circulation type approach

    Science.gov (United States)

    Mora, Carla; João Rocha, Maria; Dutra, Emanuel; Trigo, Isabel; Vieira, Gonçalo; Fragoso, Marcelo; Ramos, Miguel

    2010-05-01

    Weather types in the South Shetlands (Antarctica) were defined using an automated method based on the Lamb Weather Type classification scheme (Jones et al. 1993). This is an objective classification originally developed for the British Isles (Jones et al., 1993) and also applied to southeast (Goodess and Palutikof 1998) and northwest Spain (Lorenzo et al, 2009), Portugal (Trigo and DaCamara 2000) and Greece (Maheras et al. 2004) with good results. Daily atmospheric circulation in the South Shetlands region from 1989 to 2009 was classified using a 16-node grid of sea level pressure data from the ERA Interim. The classification is obtained through the comparison of the magnitudes of the directional and rotational components of the geostrophic flow. Basic circulation types were combined into 10 groups of weather types: four directional types (NW, N, S and SW), three anticyclonic types (A, ASW and ANW), and three cyclonic types (C, CSW and CNW). Westerly flow and cyclonic circulation are the most frequent events throughout the year. The sea level pressure field for each weather type is presented and the synoptic characteristics are described. The analysis is based on ERA-Interim fields, including mean sea level pressure, precipitation, cloud cover, humidity and air temperature. Snow thickess modelled using HTESSEL is also considered. Analysis of variance (anova) and multivariate analysis (principal component analysis) are applied to evaluate the characteristics of each weather type. This circulation-type approach showed good results in the past for the downscaling of precipitation in other regions, and we are interested in evaluating the possibilities that the classification offers for downscaling precipitation, but also for snow and air temperature. For this we will be using observational data at test sites in Livingston and Deception islands. We are also motivated by the possibility of using the circulation-type approach as a predictor in statistical downscaling

  10. Type I and type II interferons upregulate functional type I interleukin-1 receptor in a human fibroblast cell line TIG-1.

    Science.gov (United States)

    Takii, T; Niki, N; Yang, D; Kimura, H; Ito, A; Hayashi, H; Onozaki, K

    1995-12-01

    The regulation of type I interleukin-1 receptor (IL-1R) expression by type I, interferon (IFN)-alpha A/D, and type II IFN, IFN-gamma, in a human fibroblast cell line TIG-1 was investigated. After 2 h stimulation with human IFN-alpha A/D or IFN-gamma, the levels of type I IL-1R mRNA increased. We previously reported that IL-1 upregulates transcription and cell surface molecules of type I IL-1R in TIG-1 cells through induction of prostaglandin (PG) E2 and cAMP accumulation. However, indomethacin was unable to inhibit the effect of IFNs, indicating that IFNs augment IL-1R expression through a pathway distinct from that of IL-1. The augmentation was also observed in other fibroblast cell lines. Nuclear run-on assays and studies of the stability of mRNA suggested that the increase in IL-1R mRNA was a result of the enhanced transcription of IL-1R gene. Binding studies using 125I-IL-1 alpha revealed that the number of cell surface IL-1R increased with no change in binding affinity by treatment with these IFNs. Pretreatment of the cells with IFNs enhanced IL-1-induced IL-6 production, indicating that IFNs upregulate functional IL-1R. IL-1 and IFNs are produced by the same cell types, as well as by the adjacent different cell types, and are concomitantly present in lesions of immune and inflammatory reactions. These results therefore suggest that IFNs exhibit synergistic effects with IL-1 through upregulation of IL-1R. Augmented production of IL-6 may also contribute to the reactions.

  11. A Second look at the first result of Landesman-Lazer type

    Directory of Open Access Journals (Sweden)

    Alan C. Lazer

    2000-10-01

    Full Text Available We discuss some results concerning periodic and almot periodic solutions of ordinary differential equations which are precursors of a result on weak solutions of a semilinear elliptic boundary due to E. M. Landesman and the author. It is observed that in the earliest of these, if one looks for periodic solutions instead of almost peridic solutions, then the conditions can be relaxed.

  12. General boundary stabilization result of memory-type thermoelasticity with second sound

    Directory of Open Access Journals (Sweden)

    Fairouz Boulanouar

    2014-09-01

    Full Text Available In this article we consider an n-dimensional system of visco-thermoelasticity with second sound, where a viscoelastic dissipation is acting on a part of the boundary. We prove an explicit general decay rate result without imposing $u_0=0$ as in [17]. This allows a larger class of relaxation functions and initial data, hence, generalizes some previous results existing in the literature.

  13. The results of studies on clinical dosemeters type VA-J-18. Pt.1

    International Nuclear Information System (INIS)

    Penchev, V.; Buchakliev, Z.; Popits, R.; Konstantinov, B.

    1982-01-01

    A description is submitted of standard instruments used to detect and measure exposure to low and medium energy X-ray and gamma rays ( 137 Cs and 60 Co), designed for the control and calibration of dosimeters. The studies performed on clinical dosimeters, type VA-J-18, are reported. To secure exact exposure measurement, correction coefficients for non-linearity of the readings and for inaccuracy of the range factors are introduced. Non-linearity does not exceed 5 per cent of the begining of the scale, and in the range 30 to 100 scale divisions, it is within the +- 1 per cent limits. Usually, the inaccuracy of the range factors amounts to +- 3 per cent, but in isolated cases it may reach up to 10 per cent, and for that reason the second correction coefficient should be introduced as a routine in all measurements. (author)

  14. Prevalence of diagnosed and undiagnosed type 2 diabetes mellitus among US adolescents: results from the continuous NHANES, 1999-2010.

    Science.gov (United States)

    Demmer, Ryan T; Zuk, Aleksandra M; Rosenbaum, Michael; Desvarieux, Moïse

    2013-10-01

    Although prevalence and incidence of type 2 diabetes mellitus (T2DM) are reportedly increasing among adolescents, national data are lacking, particularly in regard to undiagnosed T2DM. To estimate the prevalence of diagnosed and undiagnosed T2DM among US adolescents, we analyzed a nationally representative cross-section of 11,888 adolescents aged 12-19 years who received a diabetes interview in the Continuous National Health and Nutrition Examination Survey during 1999-2010. Among them, a random subsample of 4,661 adolescents also had fasting blood samples collected. Persons who reported a previous diabetes diagnosis and were either taking no medication or taking an oral hypoglycemic agent (with or without insulin) were classified as having T2DM; persons who reported using insulin alone were classified as having type 1 diabetes. Undiagnosed diabetes was defined as a fasting plasma glucose concentration of ≥126 mg/dL and was assumed to be type 2. In the fasting subsample, 31 diabetes cases (types 1 and 2) were identified, representing a prevalence of 0.84% (weighted 95% confidence interval (CI): 0.51, 1.40) (276,638 cases; 95% CI: 134,255, 419,020). Estimates of the prevalences of type 1 and type 2 diabetes were 0.48% (95% CI: 0.23, 1.02) and 0.36% (95% CI: 0.20, 0.67), respectively, indicating that T2DM accounted for 43% of all cases. Further, undiagnosed T2DM prevalence was 0.12% (95% CI: 0.05, 0.31), representing 34% of T2DM cases (40,611 cases; 95% CI: 2,850, 78,373). T2DM accounts for approximately half of adolescent diabetes in the United States, and one-third of these cases are undiagnosed.

  15. Undifferentiated-type gastric adenocarcinoma: prognostic impact of three histological types

    Directory of Open Access Journals (Sweden)

    Lee Han

    2012-11-01

    Full Text Available Abstract Background The prognostic value of the three constituents of undifferentiated-type gastric adenocarcinoma remains unclear. The present study assessed the clinicopathological characteristics and prognosis of undifferentiated-type mucinous adenocarcinoma (uMAC and signet ring cell carcinoma (SRC compared with those of poorly differentiated adenocarcinoma (PDAC. Methods In total, 1,376 patients with undifferentiated-type gastric adenocarcinoma were included, consisting of 1,002 patients diagnosed with PDAC, 54 with uMAC and 320 with SRC. Clinicopathological factors and survival rates were compared among the three histological types. Results Significant differences in the distribution of pathological stages were observed among the groups. Patients with SRC had a significantly better survival rate than those with PDAC or uMAC, in both the all patients including non-curative resected patients and curative-resected groups. In addition, there was significant difference in survival between the PDAC and uMAC groups. Multivariate analysis suggested that age, gender, tumor depth, lymph node metastasis and curability significantly affected survival. Histological type was not an independent prognostic factor. There was no significant difference in the pattern of recurrence among the three groups. Conclusions The uMAC and SRC had worse and favorable prognosis compared with PDCA, respectively. However, there were no differences in survival by pathological stage, thus histological type was not an independent predictor of prognosis.

  16. Subtypes of batterers in treatment: empirical support for a distinction between type I, type II and type III.

    Directory of Open Access Journals (Sweden)

    José Luis Graña

    Full Text Available This study explores the existence of different types of batterers in a sample of 266 men who had been court referred for intimate partner violence. The data collected in the assessment that have been used to perform a hierarchical and a two-step cluster analysis fall into three areas: aggression towards the partner, general aggression and presence of psychopathology and personality traits, more specifically, alcohol use, borderline and antisocial personality traits, psychopathy traits, state anger and trait anger, anger expression and control, anger, hostility, and, finally, impulsivity. The results show a typology consisting of 3 types of batterers on the basis of violence level and psychopathology: low (65%, moderate (27.8% and high (7.1%. This study provides empirical support for the development of batterer typologies. These typologies will help achieve early detection of different types of batterers, allowing us to tailor interventions on the basis of the needs of each of the types.

  17. Uncertainty analysis for results of thermal hydraulic codes of best-estimate-type; Analisis de incertidumbre para resultados de codigos termohidraulicos de mejor estimacion

    Energy Technology Data Exchange (ETDEWEB)

    Alva N, J.

    2010-07-01

    In this thesis, some fundamental knowledge is presented about uncertainty analysis and about diverse methodologies applied in the study of nuclear power plant transient event analysis, particularly related to thermal hydraulics phenomena. These concepts and methodologies mentioned in this work come from a wide bibliographical research in the nuclear power subject. Methodologies for uncertainty analysis have been developed by quite diverse institutions, and they have been widely used worldwide for application to results from best-estimate-type computer codes in nuclear reactor thermal hydraulics and safety analysis. Also, the main uncertainty sources, types of uncertainties, and aspects related to best estimate modeling and methods are introduced. Once the main bases of uncertainty analysis have been set, and some of the known methodologies have been introduced, it is presented in detail the CSAU methodology, which will be applied in the analyses. The main objective of this thesis is to compare the results of an uncertainty and sensibility analysis by using the Response Surface Technique to the application of W ilks formula, apply through a loss coolant experiment and an event of rise in a BWR. Both techniques are options in the part of uncertainty and sensibility analysis of the CSAU methodology, which was developed for the analysis of transients and accidents at nuclear power plants, and it is the base of most of the methodologies used in licensing of nuclear power plants practically everywhere. Finally, the results of applying both techniques are compared and discussed. (Author)

  18. Sliding motion modulates stiffness and friction coefficient at the surface of tissue engineered cartilage.

    Science.gov (United States)

    Grad, S; Loparic, M; Peter, R; Stolz, M; Aebi, U; Alini, M

    2012-04-01

    Functional cartilage tissue engineering aims to generate grafts with a functional surface, similar to that of authentic cartilage. Bioreactors that stimulate cell-scaffold constructs by simulating natural joint movements hold great potential to generate cartilage with adequate surface properties. In this study two methods based on atomic force microscopy (AFM) were applied to obtain information about the quality of engineered graft surfaces. For better understanding of the molecule-function relationships, AFM was complemented with immunohistochemistry. Bovine chondrocytes were seeded into polyurethane scaffolds and subjected to dynamic compression, applied by a ceramic ball, for 1h daily [loading group 1 (LG1)]. In loading group 2 (LG2), the ball additionally oscillated over the scaffold, generating sliding surface motion. After 3 weeks, the surfaces of the engineered constructs were analyzed by friction force and indentation-type AFM (IT-AFM). Results were complemented and compared to immunohistochemical analyses. The loading type significantly influenced the mechanical and histological outcomes. Constructs of LG2 exhibited lowest friction coefficient and highest micro- and nanostiffness. Collagen type II and aggrecan staining were readily observed in all constructs and appeared to reach deeper areas in loaded (LG1, LG2) compared to unloaded scaffolds. Lubricin was specifically detected at the top surface of LG2. This study proposes a quantitative AFM-based functional analysis at the micrometer- and nanometer scale to evaluate the quality of cartilage surfaces. Mechanical testing (load-bearing) combined with friction analysis (gliding) can provide important information. Notably, sliding-type biomechanical stimuli may favor (re-)generation and maintenance of functional articular surfaces and support the development of mechanically competent engineered cartilage. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights

  19. Development of a Single Locus Sequence Typing (SLST) Scheme for Typing Bacterial Species Directly from Complex Communities.

    Science.gov (United States)

    Scholz, Christian F P; Jensen, Anders

    2017-01-01

    The protocol describes a computational method to develop a Single Locus Sequence Typing (SLST) scheme for typing bacterial species. The resulting scheme can be used to type bacterial isolates as well as bacterial species directly from complex communities using next-generation sequencing technologies.

  20. Types of treatment collaboration between conventional and alternative practitioners – results from a research project at a Danish MS hospital

    Directory of Open Access Journals (Sweden)

    Lasse Skovgaard

    2010-12-01

    Full Text Available Introduction: More than 50% of the People with Multiple Sclerosis (PwMS in Denmark use alternative treatment. Most of them combine alternative and conventional treatment, but PwMS often find that there is no dialogue, coordination or synergy between the parallel courses of treatment offered. For this reason the Danish Multiple Sclerosis Society conducted a research project to develop and examine different models for collaboration between conventional and alternative treatment providers. Materials and methods: Empirical material consist of individual interviews with practitioners, a group interview with practitioners, a group interview with professional staff at the Danish MS hospital that provided the organisational framework for the project, interviews with patients as well as written responses from participating treatment providers in connection with practitioner-researcher seminars held. Results: Collaboration between researchers and the treatment team resulted in the development examination of several models which describe the strengths and weaknesses of various types of collaboration. The models also show that the various types of collaboration place different requirements on the degree of 1 mutual acknowledgement and understanding among practitioners, 2 flexibility and resources in the organizational framework, and 3 patients' activities and own efforts, respectively.    Perspectives: The relationship between integration and pluralism can contribute to a fruitful discussion in regards to the value of treatment collaboration. In addition to the many positive perspectives the characterise integration of different treatment modalities the project points to the importance of not overlooking the opportunities, values and potential inherent in a pluralistic ideal in the form of patients' own active efforts and the dynamism that can arise when the patient becomes a co-informant, co-coordinator and/or co-integrator. 

  1. Analog insulin detemir for patients with type 1 and type 2 diabetes: a review

    Directory of Open Access Journals (Sweden)

    Gregory E Peterson

    2009-05-01

    Full Text Available Gregory E PetersonDepartment of Internal Medicine, Des Moines University, USAObjective: To review insulin detemir for clinical use to better manage patients with type 1 and type 2 diabetes.Methods: A MEDLINE search, in English, from June 30, 2006 to December 1, 2008, using the terms “insulin analogs,” “insulin detemir” and “long-acting insulin analog.”Results: Insulin detemir improves glycemic control, based on HbA1C reduction and fasting glucose levels, without increasing the risk of hypoglycemia and weight gain. Insulin detemir has lower glycemic variability, with less intra-subject variability in blood glucose levels in patients with type 1 and type 2 diabetes, without increasing the risk of hypoglycemia. When added to oral anti-diabetes agents (OADs in type 2 diabetes, insulin detemir demonstrates superiority to other basal insulin options.Conclusion: Insulin detemir appears to provide better glycemic control with a lower risk of hypoglycemia and less weight gain in the treatment of patients with type 1 and type 2 diabetes.Keywords: type 1 diabetes, type 2 diabetes, insulin analogs, insulin detemir

  2. Polarimetric survey of main-belt asteroids. I. Results for fifty seven S-, L-, and K-type objects

    Science.gov (United States)

    Gil-Hutton, R.; Cañada-Assandri, M.

    2011-05-01

    Aims: We present the first results of a polarimetric survey of main-belt asteroids at Complejo Astronómico El Leoncito (Casleo), San Juan, Argentina. The aims of this survey are to increase the database of asteroid polarimetry, to estimate diversity in polarimetric properties of asteroids that belong to different taxonomic classes, and to search for objects that exhibit anomalous polarimetric properties, similar to those shown by the asteroid (234) Barbara. Methods: The data were obtained with the Torino and CASPROF polarimeters at the 2.15 m telescope. The Torino polarimeter is an instrument that allows the simultaneous measurement of polarization in five different bands, and the CASPROF polarimeter is a two-hole aperture polarimeter with rapid modulation. Results: The survey began in 2003, and up to 2009 data on a sample of more than 170 asteroids were obtained. In this paper the results of 57 S-, L-, and K-type objects are presented, most of them are being polarimetrically observed for the first time. Using these data we find phase-polarization curves and polarimetric parameters for these taxonomic classes. Furthermore, we also find two candidates, (397) Vienna and (458) Hercynia, that could have a phase-polarization curve with a large inversion angle. Based on observations carried out at the Complejo Astronómico El Leoncito, operated under agreement between the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina and the National Universities of La Plata, Córdoba, and San Juan.Tables 1 and 2 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?j/A+A/529/A86

  3. A simple solution to type specialization

    DEFF Research Database (Denmark)

    Danvy, Olivier

    1998-01-01

    Partial evaluation specializes terms, but traditionally this specialization does not apply to the type of these terms. As a result, specializing, e.g., an interpreter written in a typed language, which requires a “universal” type to encode expressible values, yields residual programs with type tags...... all over. Neil Jones has stated that getting rid of these type tags was an open problem, despite possible solutions such as Torben Mogensen's “constructor specialization.” To solve this problem, John Hughes has proposed a new paradigm for partial evaluation, “Type Specialization”, based on type...... from the universal type to the specific type of the residual program. Standard partial evaluation then yields a residual program without type tags, simply and efficiently....

  4. Detecting Terrorism Incidence Type from News Summary

    DEFF Research Database (Denmark)

    Nizamani, Sarwat; Memon, Nasrullah

    2012-01-01

    The paper presents the experiments to detect terrorism incidence type from news summary data. We have applied classification techniques on news summary data to analyze the incidence and detect the type of incidence. A number of experiments are conducted using various classification algorithms...... and results show that a simple decision tree classifier can learn incidence type with satisfactory results from news data....

  5. Prospecting ideas for mesozoic granite-type, volcanics-type and exo-contact-type uranium deposits in South China. Pt.1

    International Nuclear Information System (INIS)

    Yu Dagan

    2001-01-01

    The Mesozoic uranium ore-formation process in South China resulted from the intense volcanic magmatism, the crust-mantle interaction and the fluidization in Yanshanian period, and there is great prospect for large-scale uranium concentration and ore-formation. Therefore, during the prospecting for Mesozoic granite-type, volcanics-type and exo-contact-type uranium deposits it is necessary to introduce deep-source metallogenic theory, to 'desalt' metallogenic theory of epithermal activation, to fully realize that uranium deposits may be formed not only at shallow depth, but also in conditions of deep-source, great depth and high temperature, as well as in environments of deep-source, shallow depth and median temperature, to give emphasis to the early-stage (130-95 Ma) uranium mineralization, to break the man-made boundary in prospecting for uranium only based on host rock type, to strengthen the research on Cretaceous magmatic system

  6. Long-term results after cardiac surgery in patients infected with the human immunodeficiency virus type-1 (HIV-1).

    Science.gov (United States)

    Mestres, Carlos A; Chuquiure, Javier E; Claramonte, Xavier; Muñoz, Josefa; Benito, Natividad; Castro, Miguel A; Pomar, José L; Miró, José M

    2003-06-01

    Assessment of long-term results of immunodeficiency virus type-1 (HIV-1)-infected patients undergoing cardiac surgery. Retrospective analysis of profile and outcomes of 31 HIV-1-infected patients (35 operations, 1985-2002). Twenty-seven males and four females (mean age 34.67) in three groups: acute infective endocarditis (AIE) 21 (67.74%), coronary (CAD) 5 (16.13%) and non-infective valvular disease (NIVD) 5 (16.13%). HIV factors: drug addiction (23-74.19%), homosexuality (5-16.12%), heterosexuality (3-9.67%), hemodialysis (1-3.22%). HIV stage: A (17), B (2), C (2) in AIE; A (2), B (3) in CAD and A (3), C (2) in NIVD. Mean preoperative CD4 count was 278 cells/microL (12infected patients requiring cardiac surgery, a decrease in AIE, however NIVD and CAD increasingly seen. Cardiac surgery did not blunt CD4 response induced by antiretrovirals. The late cause of death were not AIDS-related events.

  7. Health Disparities by Type of Disability: Health Examination Results of Adults (18-64 Years) with Disabilities in Shanghai, China.

    Science.gov (United States)

    Kang, Qi; Chen, Gang; Lu, Jun; Yu, Huijiong

    2016-01-01

    There have been few studies on the disparities within the population with disabilities, especially in China. The aim of this study was to evaluate the differences in some health conditions among people with different types of disabilities in Shanghai. This study was conducted using data from the Shanghai Disabled Persons' Rehabilitation Comprehensive Information Platform. The records of 31,082 persons with disabilities who had undergone professional health examination were analyzed, and the prevalence and number of five diseases and five risk factors were examined. Logistic regression was used to explore disparities from two perspectives: 1) basic differences, unadjusted for other factors, and 2) differences after adjusting for key demographic covariates. A p-value disability had a high rate of refractive error (60.0%), and averaged 1.75 diseases of interest, which was the highest value among all disability types. The mean number of risk factors we measured was greatest (1.96) in the population with mental disability. There were significant differences (p types of disabilities remained after controlling for key demographic indicators. Further research is needed to explore the relationships between health conditions and disability types.

  8. Associations between stress and migraine and tension-type headache: results from a school-based study in adolescents from grammar schools in Germany.

    Science.gov (United States)

    Milde-Busch, Astrid; Blaschek, Astrid; Heinen, Florian; Borggräfe, Ingo; Koerte, Inga; Straube, Andreas; Schankin, Christoph; von Kries, Rüdiger

    2011-05-01

    Stress is considered the major contributor to migraine and tension-type headache in adolescents. Previous studies have focused on general stressors, whereas the aim of the present study was to investigate associations between individuals' stressful experiences and different types of headache. Adolescents from 10th and 11th grades of grammar schools filled in questionnaires. Stressful experiences were measured with the Trier Inventory of Chronic Stress. Type of headache was classified according to the International Classification of Headache Disorders. Linear regressions, adjusted for sex and grade, were calculated to estimate differences in stress scores that can be attributed to migraine, tension-type headache or miscellaneous headache. A total of 1260 questionnaires were analysed. Tension-type headache, migraine and co-existing migraine plus tension-type headache were found in 48.7%, 10.2% and 19.8% of the participants. In subjects with migraine or co-existing migraine plus tension-type headache, high increases in stress scores were found in all investigated dimensions, whereas much weaker and inconsistent associations were found in subjects with tension-type headache only. The characteristic of migraine is more associated with stressful experiences than this is the case for tension-type headache. This suggests that adolescent migraine patients might especially benefit from behavioural interventions regarding stress.

  9. Typing for HLA-D/DR associated DP-antigens with the primed lymphocyte typing (PLT) technique

    DEFF Research Database (Denmark)

    Morling, N; Jakobsen, B K; Platz, P

    1980-01-01

    A total of 74 healthy unrelated random individuals and 36 patients with juvenile rheumatoid arthritis (JRA) were typed for HLA-D antigens with the homozygous typing cell technique and typed for HLA-D/DR associated DP-antigens with the primed lymphocyte typing (PLT) technique. All patients and some...... of the controls were also HLA-DR typed with a limited battery of anti-DR sera. Selected PLT-cells, specific for the HLA-D/DR antigens D/DRw1-8 and the local specificity D"H" were used. The results of the PLT-experiments were evaluated with the Normalized Median Response (NMR) method and the further procedure...

  10. A Simple Solution to Type Specialization

    DEFF Research Database (Denmark)

    Danvy, Olivier

    1998-01-01

    Partial evaluation specializes terms, but traditionally this specialization does not apply to the type of these terms. As a result, specializing, e.g., an interpreter written in a typed language, which requires a “universal” type to encode expressible values, yields residual programs with type tags...... all over. Neil Jones has stated that getting rid of these type tags was an open problem, despite possible solutions such as Torben Mogensen's “constructor specialization.” To solve this problem, John Hughes has proposed a new paradigm for partial evaluation, “Type Specialization”, based on type...... inference instead of being based on symbolic interpretation. Type Specialization is very elegant in principle but it also appears non-trivial in practice. Stating the problem in terms of types instead of in terms of type encodings suggests a very simple type-directed solution, namely, to use a projection...

  11. Glycosaminoglycans and Proteoglycans

    Directory of Open Access Journals (Sweden)

    Vitor H. Pomin

    2018-02-01

    Full Text Available In this editorial to MDPI Pharmaceuticals special issue “Glycosaminoglycans and Proteoglycans” we describe in outline the common structural features of glycosaminoglycans and the characteristics of proteoglycans, including the intracellular proteoglycan, serglycin, cell-surface proteoglycans, like syndecans and glypicans, and the extracellular matrix proteoglycans, like aggrecan, perlecan, and small leucine-rich proteoglycans. The context in which the pharmaceutical uses of glycosaminoglycans and proteoglycans are presented in this special issue is given at the very end.

  12. Results of growing relatively smoke resistant types of trees and their practical use. [German Democratic Republic

    Energy Technology Data Exchange (ETDEWEB)

    Tzschacksch, O.

    1985-01-01

    Achievements in cultivating sulfur dioxide resistant conifers in the German Democratic Republic are summarized. These conifers will be planted in afforestation programs in smoke damage zones I, i.e. in conifer forests at high elevations with maximum pollution damage. Nurseries with the most promising tree types have been established for harvesting seeds for propagation. Cultivation of cuttings and tree grafting is carried out in experimental nurseries along with laboratory gas treatment tests. Smoke resistant varieties of the common spruce Picae abies (L.) show vigorous growth in smoke damage zone I. Other spruce types suitable for cultivation are Picea pungens Engelm., Picea omorica (Panc.) Purk. with the highest vitality in 15 to 20 year old trial plantings in smoke damage zone I extreme, and Picea glanca, rubens and orientalis. Suitable pines are Pinus contorta Dougl. ex Loud. (Murray pine), Pinus mugo Turra, and others; resistant larches are Larix decidua and Larix leptolepis. Deciduous trees being cultivated for afforestation are aspens (Populus tremula L.) and mountain ash (Sorbus aucuparia L.). 11 references.

  13. Type 1 Diabetes and Interferon Therapy

    OpenAIRE

    Nakamura, Kan; Kawasaki, Eiji; Imagawa, Akihisa; Awata, Takuya; Ikegami, Hiroshi; Uchigata, Yasuko; Kobayashi, Tetsuro; Shimada, Akira; Nakanishi, Koji; Makino, Hideichi; Maruyama, Taro; Hanafusa, Toshiaki

    2011-01-01

    OBJECTIVE Interferon therapy can trigger induction of several autoimmune diseases, including type 1 diabetes. To assess the clinical, immunologic, and genetic characteristics of type 1 diabetes induced by interferon therapy, we conducted a nationwide cross-sectional survey. RESEARCH DESIGN AND METHODS Clinical characteristics, anti-islet autoantibodies, and HLA-DR typing were examined in 91 patients for whom type 1 diabetes developed during or shortly after interferon therapy. RESULTS Median ...

  14. Safety test results of lithium-thionyl chloride wound-type cells

    Science.gov (United States)

    Vallin, D.; Broussely, M.

    1989-05-01

    Increase in the use of spirally-wound, lithium-thionyl chloride cells is currently limited because of unsafe incidents which have been reported during the early stage of development of this product. Today, it is believed that these cells are safe over a wide range of operating conditions if properly designed. The paper describes the external and internal SAFT design of Li-SOCl2LSH series cells, as well as the results of safety tests.

  15. The Difference between Flux Spectrums of WH-type Assembly and CANDU-type Lattice

    International Nuclear Information System (INIS)

    Ryu, Eun Hyun; Song, Yong Mann

    2014-01-01

    The nuclear reactors are categorized by the material of the moderator because of its importance. The representative materials of the moderator are light water (H 2 O) and heavy water (D 2 O). Also, it is well known that the slowing-down ratio of D 2 O is hundreds of times larger than that of H 2 O while the slowing-down power of H 2 O is several times larger than that of D 2 O. This means that the H 2 O sometimes plays a role of an absorber such as the liquid zone controller (LZC) in a CANDU-type reactor. It is thought that the flux spectrums in a different reactor can differ from each other. In this research, two representative assemblies (the Westinghouse (WH)-type fuel assembly of PWR and the CANDU-type fuel lattice of PHWR) are selected and the flux results for each group are extracted. Although there are many codes for the lattice transport calculation, the WIMS code and the HELIOS code are used for the calculation of the WH-type fuel lattice and the CANDU-type fuel lattice. A clear difference in spectrum between the CANDU-type lattice and WH 16GD-type lattice is confirmed. Because of the superior moderating ratio of the heavy water, the thermal flux ratio of the CANDU-type lattice is almost 82%, while that of the WH 16 GD-type lattice is around 23%. Because of the large portion of the thermal flux in the CANDU-type lattice, the boron effect is maximized with the result from variations of boron. Thus it can be said that the spectrum largely depends on the moderator material, and the boron effect and sensitivity largely depends on the flux spectrum. Because of the dominant effect of the moderator material on the flux spectrum in a nuclear reactor, in the future, a comparison of the spectra of SFR, HTGR, PWR, and PHWR are also an interesting subject to study. Over-moderation in PHWR lattice and under-moderation in PWR lattice can be explained by the investigation about flux spectrums with variations of moderator density in each lattice

  16. The Difference between Flux Spectrums of WH-type Assembly and CANDU-type Lattice

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Eun Hyun; Song, Yong Mann [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    The nuclear reactors are categorized by the material of the moderator because of its importance. The representative materials of the moderator are light water (H{sub 2}O) and heavy water (D{sub 2}O). Also, it is well known that the slowing-down ratio of D{sub 2}O is hundreds of times larger than that of H{sub 2}O while the slowing-down power of H{sub 2}O is several times larger than that of D{sub 2}O. This means that the H{sub 2}O sometimes plays a role of an absorber such as the liquid zone controller (LZC) in a CANDU-type reactor. It is thought that the flux spectrums in a different reactor can differ from each other. In this research, two representative assemblies (the Westinghouse (WH)-type fuel assembly of PWR and the CANDU-type fuel lattice of PHWR) are selected and the flux results for each group are extracted. Although there are many codes for the lattice transport calculation, the WIMS code and the HELIOS code are used for the calculation of the WH-type fuel lattice and the CANDU-type fuel lattice. A clear difference in spectrum between the CANDU-type lattice and WH 16GD-type lattice is confirmed. Because of the superior moderating ratio of the heavy water, the thermal flux ratio of the CANDU-type lattice is almost 82%, while that of the WH 16 GD-type lattice is around 23%. Because of the large portion of the thermal flux in the CANDU-type lattice, the boron effect is maximized with the result from variations of boron. Thus it can be said that the spectrum largely depends on the moderator material, and the boron effect and sensitivity largely depends on the flux spectrum. Because of the dominant effect of the moderator material on the flux spectrum in a nuclear reactor, in the future, a comparison of the spectra of SFR, HTGR, PWR, and PHWR are also an interesting subject to study. Over-moderation in PHWR lattice and under-moderation in PWR lattice can be explained by the investigation about flux spectrums with variations of moderator density in each

  17. Safety test results of lithium-thionyl chloride wound-type cells

    Energy Technology Data Exchange (ETDEWEB)

    Vallin, D.; Broussely, M. (British Columbia Univ., Vancouver (Canada))

    1989-05-01

    Increase in the use of spirally-wound, lithium-thionyl chloride cells is currently limited because of unsafe incidents which have been reported during the early stage of development of this product. Today, it is believed that these cells are safe over a wide range of operating conditions if properly designed. The paper describes the external and internal SAFT design of Li-SOCl2LSH series cells, as well as the results of safety tests. 6 refs.

  18. Analysis of A-Type and B-Type Highly Polymeric Proanthocyanidins and Their Biological Activities as Nutraceuticals

    Directory of Open Access Journals (Sweden)

    Kazushige Yokota

    2013-01-01

    Full Text Available Proanthocyanidins have a series of heteroflavan-3-ols, (+-catechin/(−-epicatechin units, which are linked through a single B-type linkage and a doubly linked A-type linkage. Recently, we have performed the structural characterization of seed shells of the Japanese horse chestnut and fruits of blueberry and cranberry. The molecular sizes of them were higher in the order of blueberry > cranberry > seed shells of the Japanese horse chestnut between the respective fractions. For the analysis of terminal and extension units in those proanthocyanidins, the isolated fractions were subjected to the thiolytic cleavage of the B-type linkages using 1-dodecanethiol, and the resulting degradation products were identified by ultraperformance liquid chromatography coupled with electrospray-ionization mass spectrometry. These analyses provided fast and good resolution of the degradation products and revealed higher proportions of A-type linkages compared with B-type linkages in both isolated fractions in the order of the seed shells > cranberry > blueberry. Moreover, the isolated fractions with higher molecular sizes and those more abundant in the proportions of A-type linkages were found to be more effective in the inhibition of pancreatic lipase activity. The results suggest that A-type highly polymeric proanthocyanidins are promising for the attenuation of lipid digestion as dietary supplements.

  19. Maternal and Neonatal Outcomes in Korean Women with Type 1 and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Hee-Sook Kim

    2015-08-01

    Full Text Available BackgroundThe purpose of this study was to evaluate maternal and neonatal outcomes in Korean women with type 1 diabetes and type 2 diabetes.MethodsWe performed a retrospective survey of 163 pregnancies in women with type 1 diabetes (n=13 and type 2 diabetes (n=150 treated from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups.ResultsDifferences in glycosylated hemoglobin between type 1 and type 2 diabetes were not significant. Birth weight (3,501±689.6 g vs. 3,366±531.4 g and rate of major congenital malformations (7.7% vs. 5.6% were not significantly different. However, women with type 1 diabetes had higher rates of preeclampsia (38.5% vs. 8.2%, P=0.006, large for gestational age (LGA; 46.2% vs. 20.4%, P=0.004, macrosomia (38.5% vs. 13.4%, P=0.032, and admission for neonatal care (41.7% vs. 14.8%, P=0.03 than women with type 2 diabetes.ConclusionMaternal and neonatal outcomes for women with type 1 diabetes were poorer than for women with type 2 diabetes, especially preeclampsia, LGA, macrosomia and admission to the neonatal intensive care unit.

  20. Creatine Kinase Activity in Patients with Diabetes Mellitus Type I and Type II

    Directory of Open Access Journals (Sweden)

    Adlija Jevrić-Čaušević

    2006-08-01

    Full Text Available Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  1. [INCIDENCE OF CORONARY HEART DISEASE IN COMBINATION WITH TYPE 2 DIABETES MELLITUS ESTIMATED FROM RESULTS OF AN EPIDEMIOLOGICAL STUDY OF 20-59 YEAR OLD WOMEN].

    Science.gov (United States)

    Sultanova, S S; Kasumova, E N; Mamedova, R N

    2015-01-01

    We report evaluation of the incidence of coronary heart disease (CHD) in combination with type 2 diabetes mellitus (DM2) estimated from results of an epidemiological study of 20-59 year old women. CPD was shown to occur twice more frequently in association with DM2 especilly in the age groups of 30-39 and 50-59 years.

  2. Guarded dependent type theory with coinductive types

    DEFF Research Database (Denmark)

    Bizjak, Aleš; Grathwohl, Hans Bugge; Clouston, Ranald

    2016-01-01

    We present guarded dependent type theory, gDTT, an extensional dependent type theory with a later' modality and clock quantifiers for programming and proving with guarded recursive and coinductive types. The later modality is used to ensure the productivity of recursive definitions in a modular......, type based, way. Clock quantifiers are used for controlled elimination of the later modality and for encoding coinductive types using guarded recursive types. Key to the development of gDTT are novel type and term formers involving what we call delayed substitutions’. These generalise the applicative...... functor rules for the later modality considered in earlier work, and are crucial for programming and proving with dependent types. We show soundness of the type theory with respect to a denotational model....

  3. Delusions in first-episode psychosis: Principal component analysis of twelve types of delusions and demographic and clinical correlates of resulting domains.

    Science.gov (United States)

    Paolini, Enrico; Moretti, Patrizia; Compton, Michael T

    2016-09-30

    Although delusions represent one of the core symptoms of psychotic disorders, it is remarkable that few studies have investigated distinct delusional themes. We analyzed data from a large sample of first-episode psychosis patients (n=245) to understand relations between delusion types and demographic and clinical correlates. First, we conducted a principal component analysis (PCA) of the 12 delusion items within the Scale for the Assessment of Positive Symptoms (SAPS). Then, using the domains derived via PCA, we tested a priori hypotheses and answered exploratory research questions related to delusional content. PCA revealed five distinct components: Delusions of Influence, Grandiose/Religious Delusions, Paranoid Delusions, Negative Affect Delusions (jealousy, and sin or guilt), and Somatic Delusions. The most prevalent type of delusion was Paranoid Delusions, and such delusions were more common at older ages at onset of psychosis. The level of Delusions of Influence was correlated with the severity of hallucinations and negative symptoms. We ascertained a general relationship between different childhood adversities and delusional themes, and a specific relationship between Somatic Delusions and childhood neglect. Moreover, we found higher scores on Delusions of Influence and Negative Affect Delusions among cannabis and stimulant users. Our results support considering delusions as varied experiences with varying prevalences and correlates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Irisin Response to Two Types of Exercise Training in Type 2 Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Mousa Khalafi

    2016-09-01

    Full Text Available Abstract Background: Irisin is an exercise-induced myokine that is reduced with type 2 diabetes and improves insulin resistance via the browning of white adipose tissues. However, irisin response to two types of exercise in patients with type 2 diabetes is unknown. Materials and Methods: In this study, 22 diabetic Wistar rats (Induced by high-fat diet and injections Stz were randomly assigned to 3 groups: high intensity interval exercise (HIIT, low intensity continuous training (LICT and control (C. Both HIIT and LICT groups trained on the treadmill 5 sessions per week for 8 weeks. Blood samples were taken 24 hours after the last training session and plasma irisin, insulin and glucose levels were measured. ANOVA and Tukey post hoc tests were used to analyze data and the level of significance has been considered at p≤0.05. Results: Data analysis showed that plasma irisin levels in the HIIT group were significantly increased compared to the control group (p0.05. Plasma glucose in both HIIT and LICT groups was significantly decreased compared to the control group (p0.05. Conclusion: The results of this study showed that exercise training can increase plasma irisin in rats with type 2 diabetes. However, these changes are partially dependent on the type of exercise training.

  5. Ventilation System Type and the Resulting Classroom Temperature and Air Quality During Heating Season

    DEFF Research Database (Denmark)

    Gao, Jie; Wargocki, Pawel; Wang, Yi

    2014-01-01

    The present study investigated how different ventilation system types influence classroom temperature and air quality. Five classrooms were selected in the same school. They were ventilated by manually operable windows, manually operable windows with exhaust fan, automatically operable windows...... with and without exhaust fan and by mechanical ventilation system. Temperature, relative humidity, carbon dioxide (CO2) concentration and opening of windows were continuously monitored for one month during heating season in 2012. Classroom with manually operable windows had the highest carbon dioxide concentration...... levels so that the estimated ventilation rate was the lowest compared with the classrooms ventilated with other systems. Temperatures were slightly lower in classroom ventilated by manually operable windows with exhaust fan. Windows were opened seldom even in the classroom ventilated by manually operable...

  6. Type Inference of Turbo Pascal

    DEFF Research Database (Denmark)

    Hougaard, Ole Ildsgaard; Schwartzbach, Michael I; Askari, Hosein

    1995-01-01

    of Turbo Pascal. It has the form of a preprocessor that analyzes programs in which the type annotations are only partial or even absent. The resulting program has full type annotations, will be accepted by the standard Turbo Pascal compiler, and has polymorphic use of procedures resolved by means of code...

  7. Helicobacter pylori from Peptic Ulcer Patients in Uganda Is Highly Resistant to Clarithromycin and Fluoroquinolones: Results of the GenoType HelicoDR Test Directly Applied on Stool

    Directory of Open Access Journals (Sweden)

    Denish Calmax Angol

    2017-01-01

    Full Text Available Background. Around 70–90% of peptic ulcer disease (PUD is due to Helicobacter pylori and requires treatment with antimicrobials to which these bacteria are susceptible. Common H. pylori diagnostic tests do not provide drug susceptibility data. Using the GenoType HelicoDR PCR test designed for gastric biopsies for simultaneous detection of H. pylori and its resistance to clarithromycin (CLA/fluoroquinolones (FLQ, we present evidence for stool as an optional test specimen and also provide data on prevalence of H. pylori resistance to CLA and FLQ in Uganda. Methods. Stool from 142 symptomatic PUD patients at three hospitals in Kampala was screened for H. pylori using a rapid antigen test. The GenoType HelicoDR test was run on all H. pylori antigen positives to determine PCR positivity and resistance to CLA/FLQ. Results. Thirty-one samples (22% were H. pylori antigen positive, and 21 (68% of these were H. pylori PCR positive. Six of the 21 (29% were resistant to CLA and eight to FLQ (42%, while two gave invalid FLQ resistance results. Conclusion. Stool is a possible specimen for the GenoType HelicoDR test for rapid detection of H. pylori and drug resistance. In Uganda, Helicobacter pylori is highly resistant to CLA and FLQ.

  8. Effects of psychiatric disorders on Type A acute aortic dissection pathogenesis and analysis of follow-up results

    Directory of Open Access Journals (Sweden)

    Paolo Nardi

    2015-12-01

    Full Text Available Aims: A connection between psychiatric disorders (PDs and Type A acute aortic dissection (AAD has not been shown. The aim of this study was to define the psychological profile of patients treated for AAD, and to analyze the prevalence of PDs in their medical histories, in the immediate postoperative period, and at a mid-term follow-up. Patients and Methods: From March 2005 to October 2014, 240 consecutive patients underwent surgery for AAD. 60 patients (mean age 60+/-13 years; 43 males underwent psychiatric consultation postoperatively, and they represent the subjects of our retrospective study. Ascending aorta +/- arch replacement was performed in 43 patients, whereas the Bentall procedure +/- arch replacement was performed in 17. Data were retrospectively analyzed. Follow-ups were completed in 59 patients (mean duration 35+/-23 months. Results: PDs were present in the medical histories of 34 patients. Postoperatively, in 28 cases, a definitive diagnosis of PD (group PD was made in agreement with the diagnostic and statistical manual of mental disorders-IV criteria, including: Major depression (n=13, anxious-depressive syndrome (n=6, bipolar disorder Type 2 (n=4, panic attacks (n=2, paranoid schizophrenia (n=1, and anxiety (n=2. 32 patients without a definitive psychiatric diagnosis were classified as Group non-PD. In the postoperative period, clinical manifestations of PDs, including delirium, persistent spatio-temporal disorientation, and psychomotor agitation were evident in 22 patients (78% in group PD versus 8 patients (25% in group non-PD (P<0.0001. During follow-up, only one death for non-cardiac reasons occurred in group PD. There were no suicides; only 10 patients of group PD required PD treatment (P<0.0001 vs. early postoperative findings; 4 patients in group non-PD required PD treatment. Conclusion: Our findings suggest a strong relationship between PD and AAD. Because the psychiatric conditions appeared to be largely stable after

  9. Influence of Discussion Rating in Cooperative Learning Type Numbered Head Together on Learning Results Students VII MTSN Model Padang

    Science.gov (United States)

    Sasmita, E.; Edriati, S.; Yunita, A.

    2018-04-01

    Related to the math score of the first semester in class at seventh grade of MTSN Model Padang which much the score that low (less than KKM). It because of the students who feel less involved in learning process because the teacher don't do assessment the discussions. The solution of the problem is discussion assessment in Cooperative Learning Model type Numbered Head Together. This study aims to determine whether the discussion assessment in NHT effect on student learning outcomes of class VII MTsN Model Padang. The instrument used in this study is discussion assessment and final tests. The data analysis technique used is the simple linear regression analysis. Hypothesis test results Fcount greater than the value of Ftable then the hypothesis in this study received. So it concluded that the assessment of the discussion in NHT effect on student learning outcomes of class VII MTsN Model Padang.

  10. Macrophage galactose-type C-type lectin receptor for DC targeting of antitumor glycopeptide vaccines

    DEFF Research Database (Denmark)

    Nuti, M; Zizzari, I; Napoletano, C

    2011-01-01

    e13528 Background: Dendritic cells (DCs) are the most potent antigen presenting cells and are employed in cancer vaccination. Several receptors are being studied in order to identif strategies to increase DCs activating capacity. The C-type lectin macrophage galactose type C-type lectin (MGL...... of IFNg and IL-2 secretion by both CD8 and CD4 T cells. CONCLUSIONS: These results demonstrate that MGL engagement profoundly affects DC plasticity inducing and directing a Th1 immune response. Moreover, MGL receptor expressed on human DC can be targeted by glycopeptide based vaccines with adjuvant...

  11. Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct

    NARCIS (Netherlands)

    Romaguera, D.; Norat, T.; Wark, P.A.; Vergnaud, A.C.; Schulze, M.B.; Woudenbergh, van G.J.; Beulens, J.W.J.; Feskens, E.J.M.; The InterAct Consortium, A.

    2013-01-01

    Aims/hypothesis Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft

  12. Synthetic triterpenoids, CDDO-Imidazolide and CDDO-Ethyl amide, induce chondrogenesis.

    Science.gov (United States)

    Suh, N; Paul, S; Lee, H J; Yoon, T; Shah, N; Son, A I; Reddi, A H; Medici, D; Sporn, M B

    2012-05-01

    Novel methods for inducing chondrogenesis are critical for cartilage tissue engineering and regeneration. Here we show that the synthetic oleanane triterpenoids, CDDO-Imidazolide (CDDO-Im) and CDDO-Ethyl amide (CDDO-EA), at concentrations as low as 200 nM, induce chondrogenesis in organ cultures of newborn mouse calvaria. The cartilage phenotype was measured histologically with metachromatic toluidine blue staining for proteoglycans and by immunohistochemical staining for type II collagen. Furthermore, real-time polymerase chain reaction (PCR) analysis using mRNA from calvaria after 7-day treatment with CDDO-Im and CDDO-EA showed up-regulation of the chondrocyte markers SOX9 and type II collagen (alpha1). In addition, TGF-β; BMPs 2 and 4; Smads 3, 4, 6, and 7; and TIMPs-1 and -2 were increased. In contrast, MMP-9 was strongly down-regulated. Treatment of human bone marrow-derived mesenchymal stem cells with CDDO-Im and CDDO-EA (100 nM) induced expression of SOX9, collagen IIα1, and aggrecan, as well as BMP-2 and phospho-Smad5, confirming that the above triterpenoids induce chondrogenic differentiation. This is the first report of the use of these drugs for induction of chondrogenesis. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  13. Electrical stimulation drives chondrogenesis of mesenchymal stem cells in the absence of exogenous growth factors

    Science.gov (United States)

    Kwon, Hyuck Joon; Lee, Gyu Seok; Chun, Honggu

    2016-01-01

    Electrical stimulation (ES) is known to guide the development and regeneration of many tissues. However, although preclinical and clinical studies have demonstrated superior effects of ES on cartilage repair, the effects of ES on chondrogenesis remain elusive. Since mesenchyme stem cells (MSCs) have high therapeutic potential for cartilage regeneration, we investigated the actions of ES during chondrogenesis of MSCs. Herein, we demonstrate for the first time that ES enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels, thereby inducing differentiation of MSCs into hyaline chondrogenic cells without the addition of exogenous growth factors. ES also induced MSC condensation and subsequent chondrogenesis by driving Ca2+/ATP oscillations, which are known to be essential for prechondrogenic condensation. In subsequent experiments, the effects of ES on ATP oscillations and chondrogenesis were dependent on extracellular ATP signaling via P2X4 receptors, and ES induced significant increases in TGF-β1 and BMP2 expression. However, the inhibition of TGF-β signaling blocked ES-driven condensation, whereas the inhibition of BMP signaling did not, indicating that TGF-β signaling but not BMP signaling mediates ES-driven condensation. These findings may contribute to the development of electrotherapeutic strategies for cartilage repair using MSCs. PMID:28004813

  14. Tissue engineering applications: cartilage lesions repair by the use of autologous chondrocytes

    Directory of Open Access Journals (Sweden)

    L. De Franceschi

    2011-09-01

    Full Text Available Promising new therapies based on tissue engineering have been recently developed for cartilage repair. The association of biomaterials with autologous chondrocytes expanded in vitro can represent a useful tool to regenerate this tissue. The scaffolds utilised in such therapeutical applications should provide a pre-formed three-dimensional shape, prevent cells from floating out of the defect, have sufficient mechanical strength, facilitate uniform spread of cells and stimulate the phenotype of transplanted cells. Hyaff®-11 is a hyaluronic-acid based biodegradable polymer, that has been shown to provide successful cell carrier for tissue-engineered repair. From our findings we can state that human chondrocytes seeded on Hyaff®-11 are able to maintain in vitro the characteristic of differentiated cells, expressing and producing collagen type II and aggrecan which are the main markers of cartilage phenotype, down-regulating collagen type I. Moreover, it seems to be a useful scaffold for cartilage repair both in animal models and clinical trials in humans, favouring the formation of a hyaline-like tissue. In the light of these data, we can hypothesise, for the future, the use of autologous chondrocyte transplantation together with gene therapy as a treatment for rheumatic diseases such as osteoarthritis.

  15. Characterization of cells from pannus-like tissue over articular cartilage of advanced osteoarthritis.

    Science.gov (United States)

    Yuan, G-H; Tanaka, M; Masuko-Hongo, K; Shibakawa, A; Kato, T; Nishioka, K; Nakamura, H

    2004-01-01

    To identify the characteristics of cells isolated from pannus-like soft tissue on osteoarthritic cartilage (OA pannus cells), and to evaluate the role of this tissue in osteoarthritis (OA). OA pannus cells were isolated from pannus-like tissues in five joints obtained during arthroplasty. The phenotypic features of the isolated cells were characterized by safranin-O staining and immunohistochemical studies. Expression of MMP-1, MMP-3 and MMP-13 was also assessed using reverse transcriptase-polymerase chain reactions (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry. Foci and plaque formation of pannus-like tissue over cartilage surface were found in 15 of 21 (71.4%) OA joints macroscopically, and among them, only five samples had enough tissue to be isolated. OA pannus cells were positive for type I collagen and vimentin, besides they also expressed type II collagen and aggrecan mRNA. Spontaneous expression of MMP-1, MMP-3 and MMP-13 was detected in OA pannus cells. Similar or higher levels of MMPs were detected in the supernatant of cultured OA pannus cells compared to OA chondrocytes, and among these MMP-3 levels were relatively higher in OA pannus cells. Immunohistochemically, MMP-3 positive cells located preferentially in pannus-like tissue on the border of original hyaline cartilage. Our results showed that OA pannus cells shared the property of mesenchymal cells and chondrocytes; however, their origin seemed different from chondrocytes or synoviocytes. The spontaneous expression of MMPs suggests that they are involved in the articular degradation in OA.

  16. Type 1 Diabetes and Sleep

    OpenAIRE

    Farabi, Sarah S.

    2016-01-01

    IN BRIEF In people with type 1 diabetes, sleep may be disrupted as a result of both behavioral and physiological aspects of diabetes and its management. This sleep disruption may negatively affect disease progression and development of complications. This review highlights key research findings regarding sleep in people with type 1 diabetes.

  17. Influence of evidence type and narrative type on HPV risk perception and intention to obtain the HPV vaccine.

    Science.gov (United States)

    Nan, Xiaoli; Dahlstrom, Michael F; Richards, Adam; Rangarajan, Sarani

    2015-01-01

    This research examines the influence of evidence type (statistical, narrative, or hybrid) and narrative type (first-person or third-person) on risk perception about human papillomavirus (HPV) and behavioral intention to get the HPV vaccine. In total, 174 college students who had not received the HPV vaccine participated in a controlled experiment. Results show that the hybrid message containing both statistical and narrative descriptions of HPV resulted in greater perceived risk of getting HPV than either of the messages containing just one type of evidence--statistical or narrative. Moreover, the first-person narrative message led to greater risk perception about HPV than the third-person narrative message. Both evidence type and narrative type had an indirect effect on intention to get the HPV vaccine free of cost through HPV risk perception. Implications of the findings for vaccine risk communication are discussed.

  18. Memoization in Type-Directed Partial Evaluation

    DEFF Research Database (Denmark)

    Balat, Vincent; Danvy, Olivier

    2002-01-01

    We use a code generator—type-directed partial evaluation— to verify conversions between isomorphic types, or more precisely to verify that a composite function is the identity function at some complicated type. A typed functional language such as ML provides a natural support to express the funct......We use a code generator—type-directed partial evaluation— to verify conversions between isomorphic types, or more precisely to verify that a composite function is the identity function at some complicated type. A typed functional language such as ML provides a natural support to express...... originate in the handling of sums, which uses delimited continuations. We successfully eliminate these redundancies by extending type-directed partial evaluation with memoization capabilities. The result only works for pure functional programs, but it provides an unexpected use of code generation...... and it yields orders-of-magnitude improvements both in time and in space for type isomorphisms. Basic Research in Computer Science (www. brics. dk), funded by the Danish National Research Foundation....

  19. Study of Type III ELMs in JET

    Energy Technology Data Exchange (ETDEWEB)

    Sartori, R [EFDA Close Support Unit, Garching, 2 Boltzmannstrasse, Garching (Germany); Saibene, G [EFDA Close Support Unit, Garching, 2 Boltzmannstrasse, Garching (Germany); Horton, L D [Association Euratom-IPP, MPI fuer Plasmaphysik, 2 Boltzmannstrasse, Garching (Germany); Becoulet, M [Association Euratom-CEA, CE Cadarache, F-13108 St Paul-lez-Durance, CEDEX (France); Budny, R [PPPL, Princeton University, PO Box 451, Princeton, NJ 08543 (United States); Borba, D [Associacao EURATOM/IST, Centro de Fusao Nuclear, 1096 Lisbon, CODEX (Portugal); Chankin, A [Association Euratom-IPP, MPI fuer Plasmaphysik, 2 Boltzmannstrasse, Garching (Germany); Conway, G D [Association Euratom-IPP, MPI fuer Plasmaphysik, 2 Boltzmannstrasse, Garching (Germany); Cordey, G [EURATOM-UKAEA Fusion Association, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); McDonald, D [EURATOM-UKAEA Fusion Association, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Guenther, K [EURATOM-UKAEA Fusion Association, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Hellermann, M G von [FOM-Rijnhuizen, Ass. Euratom-FOM, TEC, PO Box 1207, 3430 BE Nieuwegein (Netherlands); Igithkanov, Yu [Max-Planck-Institute for Plasma Physics, Teilinstitut Greifswald, EURATOM Ass., D-17491, Greifswald (Germany); Loarte, A [EFDA Close Support Unit, Garching, 2 Boltzmannstrasse, Garching (Germany); Lomas, P J [EURATOM-UKAEA Fusion Association, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Pogutse, O [EURATOM-UKAEA Fusion Association, Culham Science Centre, Abingdon, OX14 3DB (United Kingdom); Rapp, J [EFDA Close Support Unit, Culham, Abingdon OX14 3DB (United Kingdom)

    2004-05-01

    This paper presents the results of JET experiments aimed at studying the operational space of plasmas with a Type III ELMy edge, in terms of both local and global plasma parameters. In JET, the Type III ELMy regime has a wide operational space in the pedestal n{sub e} - T{sub e} diagram, and Type III ELMs are observed in standard ELMy H-modes as well as in plasmas with an internal transport barrier (ITB). The transition from an H-mode with Type III ELMs to a steady state Type I ELMy H-mode requires a minimum loss power, P{sub TypeI}. P{sub TypeI} decreases with increasing plasma triangularity. In the pedestal n{sub e} - T{sub e} diagram, the critical pedestal temperature for the transition to Type I ELMs is found to be inversely proportional to the pedestal density (T{sub crit} {proportional_to} 1/n) at a low density. In contrast, at a high density, T{sub crit}, does not depend strongly on density. In the density range where T{sub crit} {proportional_to} 1/n, the critical power required for the transition to Type I ELMs decreases with increasing density. Experimental results are presented suggesting a common mechanism for Type III ELMs at low and high collisionality. A single model for the critical temperature for the transition from Type III to Type I ELMs, based on the resistive interchange instability with magnetic flutter, fits well the density and toroidal field dependence of the JET experimental data. On the other hand, this model fails to describe the variation of the Type III n{sub e} - T{sub e} operational space with isotopic mass and q{sub 95}. Other results are instead suggestive of a different physics for Type III ELMs. At low collisionality, plasma current ramp experiments indicate a role of the edge current in determining the transition from Type III to Type I ELMs, while at high collisionality, a model based on resistive ballooning instability well reproduces, in term of a critical density, the experimentally observed q{sub 95} dependence of the

  20. Fertility treatment and childhood type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Kettner, Laura Ozer; Matthiesen, Niels Bjerregaard; Ramlau-Hansen, Cecilia Høst

    2016-01-01

    OBJECTIVE: To investigate the association between specific types of fertility treatment and childhood type 1 diabetes mellitus. DESIGN: Nationwide birth cohort study. SETTING: Not applicable. PATIENT(S): All pregnancies resulting in a live-born singleton child in Denmark from 1995 to 2003....... INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Childhood type 1 diabetes mellitus identified from redeemed prescriptions for insulin until 2013. RESULT(S): The study included 565,116 singleton pregnancies. A total of 14,985 children were conceived by ovulation induction or intrauterine insemination......, and 8,490 children were conceived by in vitro fertilization or intracytoplasmic sperm injection. During the follow-up period, 2,011 (0.4%) children developed type 1 diabetes mellitus. The primary analyses showed no association between fertility treatment and childhood type 1 diabetes mellitus...

  1. Timing of blood transfusion and not ABO blood type is associated with survival in patients treated with radical cystectomy for nonmetastatic bladder cancer: Results from a single high-volume institution.

    Science.gov (United States)

    Moschini, Marco; Bianchi, Marco; Rossi, Martina Sofia; Dell׳Oglio, Paolo; Gandaglia, Giorgio; Fossati, Nicola; Mattei, Agostino; Damiano, Rocco; Shariat, Shahrokh F; Salonia, Andrea; Montorsi, Francesco; Briganti, Alberto; Colombo, Renzo; Gallina, Andrea

    2016-06-01

    Perioperative transfusions have been recently associated to poor outcomes as an indirect consequence of immune-hematological changes related to transfusion itself and blood type. We tested the role of blood transfusion on cancer-specific mortality (CSM) and overall mortality (OM), considering the effect of ABO system, Rh factor, and timing of transfusions. The study focused on 728 patients with bladder cancer treated with radical cystectomy at a single tertiary care referral center between January 1995 and August 2013 with complete ABO blood type information. Kaplan-Meier analysis was used to assess the effect of transfusions, stratified according to ABO type and Rh factor, on CSM and OM. The same endpoints were tested in Cox regression models, after adjusting for all available confounders. A total of 341 (46.8%), 277 (38.0%), 83 (11.4%), and 27 (3.7%) patients had blood type O, A, B and AB, respectively. Overall, 630 (86.5%) and 98 (13.5%) patients were Rh-and Rh+, respectively. At a median follow-up time of 65 months, 225 (30.9%) and 282 (38.7%) patients recorded CSM and OM, respectively. At univariable analyses, ABO blood type and Rh status were not associated to either CSM or OM (all P>0.2). Similar results were observed when ABO blood type and Rh factor were tested in multivariable models (all P>0.3). Conversely, Charlson score, preoperative hemoglobin, number of nodes removed, pathological T stage, and number of positive nodes were associated to both CSM and OM (all Pblood units in the postoperative period (P>0.05) was associated with an increase of CSM and OM. Although ABO type or Rh factor or both were associated with several adverse outcomes in many cancers, we were not able to confirm this association in bladder cancer. Based on our results, the effect of transfusion on survival is independent by ABO type but is associated to the timing of blood supply administration. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Early onset type 2 diabetes

    DEFF Research Database (Denmark)

    Bo, A; Thomsen, R W; Nielsen, J S

    2018-01-01

    was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age-gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2......AIM: To examine the association between early onset of type 2 diabetes (DM) and clinical and behavioural risk factors for later diabetes complications. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic...... Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early-onset) with diagnosis age 46-55, 56-65 (average-onset = reference), 66-75, and >75 years (late-onset). Prevalence ratios (PRs) were computed using Poisson regression. RESULTS: Poor...

  3. Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study.

    Science.gov (United States)

    Raab, Jennifer; Haupt, Florian; Scholz, Marlon; Matzke, Claudia; Warncke, Katharina; Lange, Karin; Assfalg, Robin; Weininger, Katharina; Wittich, Susanne; Löbner, Stephanie; Beyerlein, Andreas; Nennstiel-Ratzel, Uta; Lang, Martin; Laub, Otto; Dunstheimer, Desiree; Bonifacio, Ezio; Achenbach, Peter; Winkler, Christiane; Ziegler, Anette-G

    2016-05-18

    Type 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care. Children aged 2-5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed. Of the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies. Staging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education. The study was approved by the ethics committee of Technische Universität München (Nr. 70/14). Published by the BMJ Publishing Group Limited. For

  4. An Automatic Lab-on-Disc System for Blood Typing.

    Science.gov (United States)

    Chang, Yaw-Jen; Fan, Yi-Hua; Chen, Shia-Chung; Lee, Kuan-Hua; Lou, Liao-Yong

    2018-04-01

    A blood-typing assay is a critical test to ensure the serological compatibility of a donor and an intended recipient prior to a blood transfusion. This article presents a lab-on-disc blood-typing system to conduct a total of eight assays for a patient, including forward-typing tests, reverse-typing tests, and irregular-antibody tests. These assays are carried out in a microfluidic disc simultaneously. A blood-typing apparatus was designed to automatically manipulate the disc. The blood type can be determined by integrating the results of red blood cell (RBC) agglutination in the microchannels. The experimental results of our current 40 blood samples show that the results agree with those examined in the hospital. The accuracy reaches 97.5%.

  5. Gelatin- and starch-based hydrogels. Part A: Hydrogel development, characterization and coating.

    Science.gov (United States)

    Van Nieuwenhove, Ine; Salamon, Achim; Peters, Kirsten; Graulus, Geert-Jan; Martins, José C; Frankel, Daniel; Kersemans, Ken; De Vos, Filip; Van Vlierberghe, Sandra; Dubruel, Peter

    2016-11-05

    The present work aims at constructing the ideal scaffold matrix of which the physico-chemical properties can be altered according to the targeted tissue regeneration application. Ideally, this scaffold should resemble the natural extracellular matrix (ECM) as close as possible both in terms of chemical composition and mechanical properties. Therefore, hydrogel films were developed consisting of methacrylamide-modified gelatin and starch-pentenoate building blocks because the ECM can be considered as a crosslinked hydrogel network consisting of both polysaccharides and structural, signaling and cell-adhesive proteins. For the gelatin hydrogels, three different substitution degrees were evaluated including 31%, 72% and 95%. A substitution degree of 32% was applied for the starch-pentenoate building block. Pure gelatin hydrogels films as well as interpenetrating networks with gelatin and starch were developed. Subsequently, these films were characterized using gel fraction and swelling experiments, high resolution-magic angle spinning (1)H NMR spectroscopy, rheology, infrared mapping and atomic force microscopy. The results indicate that both the mechanical properties and the swelling extent of the developed hydrogel films can be controlled by varying the chemical composition and the degree of substitution of the methacrylamide-modified gelatin applied. The storage moduli of the developed materials ranged between 14 and 63kPa. Phase separation was observed for the IPNs for which separated starch domains could be distinguished located in the surrounding gelatin matrix. Furthermore, we evaluated the affinity of aggrecan for gelatin by atomic force microscopy and radiolabeling experiments. We found that aggrecan can be applied as a bioactive coating for gelatin hydrogels by a straightforward physisorption procedure. Thus, we achieved distinct fine-tuning of the physico-chemical properties of these hydrogels which render them promising candidates for tissue engineering

  6. Adiposity Impacts Intrarenal Hemodynamic Function in Adults With Long-standing Type 1 Diabetes With and Without Diabetic Nephropathy: Results From the Canadian Study of Longevity in Type 1 Diabetes.

    Science.gov (United States)

    Bjornstad, Petter; Lovshin, Julie A; Lytvyn, Yuliya; Boulet, Genevieve; Lovblom, Leif E; Alhuzaim, Omar N; Farooqi, Mohammed A; Lai, Vesta; Tse, Josephine; Cham, Leslie; Orszag, Andrej; Scarr, Daniel; Weisman, Alanna; Keenan, Hillary A; Brent, Michael H; Paul, Narinder; Bril, Vera; Perkins, Bruce A; Cherney, David Z I

    2018-04-01

    Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). Patients with type 1 diabetes ( n = 66, duration ≥50 years) and age-/sex-matched control subjects ( n = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m 2 and inulin [GFR INULIN ], effective renal plasma flow for p -aminohippuric acid [ERPF PAH ]) was measured. Afferent arteriolar resistance, efferent arteriolar resistance, renal blood flow, renal vascular resistance [RVR], filtration fraction, and glomerular pressure were derived from the Gomez equations. Fat and lean mass were quantified by DXA. Whereas measures of adiposity did not associate with GFR INULIN or ERPF PAH in healthy control subjects, trunk fat mass inversely correlated with GFR INULIN ( r = -0.46, P INULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPF PAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function. © 2018 by the American Diabetes Association.

  7. Type Families with Class, Type Classes with Family

    DEFF Research Database (Denmark)

    Serrano, Alejandro; Hage, Jurriaan; Bahr, Patrick

    2015-01-01

    Type classes and type families are key ingredients in Haskell programming. Type classes were introduced to deal with ad-hoc polymorphism, although with the introduction of functional dependencies, their use expanded to type-level programming. Type families also allow encoding type-level functions......, now as rewrite rules. This paper looks at the interplay of type classes and type families, and how to deal with shortcomings in both of them. Furthermore, we show how to use families to simulate classes at the type level. However, type families alone are not enough for simulating a central feature...... of type classes: elaboration, that is, generating code from the derivation of a rewriting. We look at ways to solve this problem in current Haskell, and propose an extension to allow elaboration during the rewriting phase....

  8. The impact of the types of microorganisms isolated from blood and wounds on the results of treatment in burn patients with sepsis.

    Science.gov (United States)

    Glik, Justyna; Kawecki, Marek; Gaździk, Tadeusz; Nowak, Mariusz

    2012-01-01

    Despite development of combustiology, infections continue to be the most important cause of death among patients with burns. Sepsis is the most severe clinical presentation of infection in patients after thermal injuries who require immediate treatment. Early diagnosis and proper treatment of sepsis are important in the clinical management that is often hampered for multiple reasons, e.g. impaired patient immunity, problems with microorganisms with multi-antibacterial drug resistance. The aim of the study was to assess effect of type of a microorganism isolated from blood and wound on results of treatment of sepsis in patients with burns. Effect of type of microorganisms isolated from blood and wound on the result of treatment of sepsis was studied in 338 patients hospitalized immediately after an injury in Centre for Burn Treatment in Siemianowice Śląskie in years 2003 - 2004 (at the age of 18 - 96 years, 66 women and 272 men). Clinical symptoms of generalized infection were found in all study subjects. The study group was divided into two subgroups: cured patients and patients who died of sepsis. The following parameters were assessed in both subgroups: type of microorganism isolated from blood, type of microorganism isolated from wound as well as occurrence of the same and different infections of blood and burn wound. positive blood cultures were found in 165 patients (48.8%), 106 (64.2%) were cured, 59 (35.8%) died. The most commonly isolated microorganisms in cured patients were Gram(+) Staphylococcus epidermidis MRSE (19.81%) and Staphylococcus aureus MRSA (18.87%). Gram(-) intestinal rods were least commonly isolated from this group. The most commonly isolated microorganisms from blood of patients who were to die, included non-fermenting Gram(-) rods Acinetobacter baumannii (35.59%) and Pseudomonas aeruginosa (22.03%). Mixed bacterial flora was found in the blood of 22.03% patients. Among patients who were to die, the same microorganisms were found in the

  9. Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

    Science.gov (United States)

    Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

    2014-09-01

    An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Insights into optimal basal insulin titration in type 2 diabetes: Results of a quantitative survey.

    Science.gov (United States)

    Berard, Lori; Bonnemaire, Mireille; Mical, Marie; Edelman, Steve

    2018-02-01

    Basal insulin (BI) treatment initiation and dose titration in type 2 diabetes (T2DM) are often delayed. Such "clinical inertia" results in poor glycaemic control and high risk of long-term complications. This survey aimed to determine healthcare professional (HCP) and patient attitudes to BI initiation and titration. An online survey (July-August 2015) including HCPs and patients with T2DM in the USA, France and Germany. Patients were ≥18 years old and had been on BI for 6 to 36 months, or discontinued BI within the previous 12 months. Participants comprised 386 HCPs and 318 people with T2DM. While >75% of HCPs reported discussing titration at the initiation visit, only 16% to 28% of patients remembered such discussions, many (32%-42%) were unaware of the need to titrate BI, and only 28% to 39% recalled mention of the time needed to reach glycaemic goals. Most HCPs and patients agreed that more effective support tools to assist BI initiation/titration are needed; patients indicated that provision of such tools would increase confidence in self-titration. HCPs identified fear of hypoglycaemia, failure to titrate in the absence of symptoms, and low patient motivation as important titration barriers. In contrast, patients identified weight gain, the perception that titration meant worsening disease, frustration over the time to reach HbA1c goals and fear of hypoglycaemia as major factors. A disconnect exists between HCP- and patient-perceived barriers to effective BI titration. To optimize titration, strategies should be targeted to improve HCP-patient communication, and provide support and educational tools. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  11. Static Test and Result Analysis on Different Types of Pile Composite Foundation in the Same Field

    Directory of Open Access Journals (Sweden)

    Zhao Tuo

    2015-01-01

    Full Text Available Combining with the situation of soil test site, the large scale experiment was studying about natural foundation, rammed soil-cement piles, CFG pile and gravel pil. A series of conclusions were given from p-s curve, the fitting curve, and the Angle of the stress ratio of pile-soil composite modulus. It has certain guiding significance for the design and construction of pile type, which is used in North China area.

  12. Single-channel L-type Ca2+ currents in chicken embryo semicircular canal type I and type II hair cells.

    Science.gov (United States)

    Zampini, Valeria; Valli, Paolo; Zucca, Giampiero; Masetto, Sergio

    2006-08-01

    Few data are available concerning single Ca channel properties in inner ear hair cells and particularly none in vestibular type I hair cells. By using the cell-attached configuration of the patch-clamp technique in combination with the semicircular canal crista slice preparation, we determined the elementary properties of voltage-dependent Ca channels in chicken embryo type I and type II hair cells. The pipette solutions included Bay K 8644. With 70 mM Ba(2+) in the patch pipette, Ca channel activity appeared as very brief openings at -60 mV. Ca channel properties were found to be similar in type I and type II hair cells; therefore data were pooled. The mean inward current amplitude was -1.3 +/- 0.1 (SD) pA at - 30 mV (n = 16). The average slope conductance was 21 pS (n = 20). With 5 mM Ba(2+) in the patch pipette, very brief openings were already detectable at -80 mV. The mean inward current amplitude was -0.7 +/- 0.2 pA at -40 mV (n = 9). The average slope conductance was 11 pS (n = 9). The mean open time and the open probability increased significantly with depolarization. Ca channel activity was still present and unaffected when omega-agatoxin IVA (2 microM) and omega-conotoxin GVIA (3.2 microM) were added to the pipette solution. Our results show that types I and II hair cells express L-type Ca channels with similar properties. Moreover, they suggest that in vivo Ca(2+) influx might occur at membrane voltages more negative than -60 mV.

  13. APPLICATION OF COOPERATIVE LEARNING MODEL INDEX CARD MATCH TYPE IN IMPROVING STUDENT LEARNING RESULTS ON COMPOSITION AND COMPOSITION FUNCTIONS OF FUNCTIONS INVERS IN MAN 1 MATARAM

    Directory of Open Access Journals (Sweden)

    Syahrir Syahrir

    2017-12-01

    Full Text Available Lack of student response in learning mathematics caused by passive of student in process of learning progress so that student consider mathematics subject is difficult subject to be understood. The research is Classroom Action Research (PTK using 2 cycles, then the purpose of this research is how the implementation of cooperative learning type of index card match in improving student learning outcomes on the subject matter of composition function and inverse function in MAN 1 Mataram. While the results of the analysis in the study showed that there is in cycle I obtained classical completeness 78.79% with the average score of student learning outcomes 69.78 and the average value of student learning responses with the category Enough, then in cycle II shows that classical thoroughness 87 , 89% with mean score of student learning result 78,94 and average value of student learning response with good category. So it can be concluded that the implementation of Model Cooperative Learning Type Index Card Match can improve student learning outcomes on the subject matter of composition function and inverse function.

  14. Results of theoretical studies on power noise of PWR type reactors

    International Nuclear Information System (INIS)

    Meyer, K.

    1979-12-01

    For evaluating noise measurements of neutron flux in power reactors position-dependent effects are taken into account. Based on an effective one-group diffusion model results are obtained for reactor noise due to vibrating control elements and disturbances in the coolant flow

  15. Results of radioiodine treatment in various types of hyperthyroidism

    International Nuclear Information System (INIS)

    Donner, C.S.

    1988-01-01

    During an investigation period starting early in 1982 and ending in the middle of 1985 a total of 360 patients were treated with iodine-131 for hyperthyroidism of different origins. The case reports of 337 of these patients were reviewed for the purposes of this study. The patients were divided into three groups. In this cohort, the healing rates achieved with one single treatment were 84.4% for autonomic adenomas, 50.8% for hyperthyroidism of other than immunologic origins and 22.7% for Basedow's disease. After a series of up to four treatments the healing rates were seen to be increased to 93% for autonomous adenomas, 84% for nonimmunogenic hyperthyroidism and 80% for Basedow's disease. The results thus achieved appeared to be unrelated to the patients' sex or previous surgical interventions for disorders of the thyroid. The findings show that therapeutic regimes calculated individually on the basis of a formula should be approached with some caution. Thus, doses lower than 100 Gy are hardly advisable for patients showing diffuse hyperthyroidism. It would also appear wise in autonomous adenomas to reduce the dose from 400 to 200 Gy. Likewise, the use of doses above 15 mCi should be restricted to special cases. A dose-effect relationship could not be detected in patients suffering from Basedow's disease. It seems recommendable here to use low initial doses so as to permit less radiosensitive patients to be healed by repeat treatment with a higher dose. (orig./MG) [de

  16. Human cartilaginous endplate degeneration is induced by calcium and the extracellular calcium-sensing receptor in the intervertebral disc

    Directory of Open Access Journals (Sweden)

    MP Grant

    2016-07-01

    Full Text Available The cartilaginous endplates (CEPs are thin layers of hyaline cartilage found adjacent to intervertebral discs (IVDs. In addition to providing structural support, CEPs regulate nutrient and metabolic exchange in the disc. In IVD pathogenesis, CEP undergoes degeneration and calcification, compromising nutrient availability and disc cell metabolism. The mechanism(s underlying the biochemical changes of CEP in disc degeneration are currently unknown. Since calcification is often observed in later stages of IVD degeneration, we hypothesised that elevations in free calcium (Ca2+ impair CEP homeostasis. Indeed, our results demonstrated that the Ca2+ content was consistently higher in human CEP tissue with grade of disc degeneration. Increasing the levels of Ca2+ resulted in decreases in the secretion and accumulation of collagens type I, II and proteoglycan in cultured human CEP cells. Ca2+ exerted its effects on CEP matrix protein synthesis through activation of the extracellular calcium-sensing receptor (CaSR; however, aggrecan content was also affected independent of CaSR activation as increases in Ca2+ directly enhanced the activity of aggrecanases. Finally, supplementing Ca2+ in our IVD organ cultures was sufficient to induce degeneration and increase the mineralisation of CEP, and decrease the diffusion of glucose into the disc. Thus, any attempt to induce anabolic repair of the disc without addressing Ca2+ may be impaired, as the increased metabolic demand of IVD cells would be compromised by decreases in the permeability of the CEP.

  17. Middle-term follow-up results of Pipkin type IV femoral head fracture patients treated by reconstruction plate and bioabsorbable screws

    Directory of Open Access Journals (Sweden)

    Shan-Xi Wang

    2018-06-01

    Full Text Available Purpose: To investigate the mid-term curative effects of the treatment of Pipkin type IV femoral head fractures using a reconstruction plate and bioabsorbable screws and provide the evidence for clinical practice. Methods: From February 2010 to September 2014, 21 patients with Pipkin type IV femoral head fractures were treated surgically. There were 13 males and 8 females with an average age of 41.1 years (range, 20–65 years. The causes of the fractures included traffic accidents (13 cases, falls from a height (four cases, heavy lifting injuries (three cases, and sport injury (one case. All patients were followed up with radiography and three-dimensional reconstruction computed tomography and other checks and any complications were actively managed. Closed reduction of fracture-dislocation of the hip was attempted under general anesthesia using the Kocher-Langenbeck approach. Femoral head fractures were treated with internal fixation or excision based on the size of the fracture fragments, whereas acetabular fractures were fixed with a reconstruction plate and screws following anatomic reduction. Results: The incisions healed by primary intention in all patients after surgery, without any infection, deep venous thrombosis, or other complications. All 21 patients were followed up for 36–76 months, with an average follow-up duration of 49 months. Postoperative imaging data showed that all dislocations and fractures were anatomically reduced, and bony union of the fractures was achieved. Heterotopic ossification was found in four patients, post-traumatic osteoarthritis in three, and avascular necrosis of the femoral head in two. At the final follow-up, the assessment of hip joint function according to the Thompson-Epstein scoring scale was excellent in 10 cases, good in six cases, fair in three cases, and poor in two cases. The rate of excellent and good functional outcomes was 76.1%. Conclusion: The mid-term curative effects of a

  18. [Diagnostic values of serum type III procollagen N-terminal peptide in type IV gastric cancer].

    Science.gov (United States)

    Akazawa, S; Fujiki, T; Kanda, Y; Kumai, R; Yoshida, S

    1985-04-01

    Since increased synthesis of collagen has been demonstrated in tissue of type IV gastric cancer, we attempted to distinguish type IV gastric cancer from other cancers by measuring serum levels of type III procollagen N-terminal peptide (type III-N-peptide). Mean serum levels in type IV gastric cancer patients without metastasis were found to be elevated above normal values and developed a tendency to be higher than those in types I, II and III gastric cancer patients without metastasis. Highly positive ratios were found in patients with liver diseases including hepatoma and colon cancer, biliary tract cancer, and esophageal cancer patients with liver, lung or bone metastasis, but only 2 out of 14 of these cancer patients without such metastasis showed positive serum levels of type III-N-peptide. Positive cases in patients with type IV gastric cancer were obtained not only in the group with clinical stage IV but also in the groups with clinical stages II and III. In addition, high serum levels of type III-N-peptide in patients with type IV gastric cancer were seen not only in the cases with liver, lung or bone metastasis but also in cases with disseminated peritoneal metastasis alone. These results suggest that if the serum level of type III-N-peptide is elevated above normal values, type IV gastric cancer should be suspected after ruling out liver diseases, myelofibrosis and liver, lung or bone metastasis.

  19. spa Typing and Multilocus Sequence Typing Show Comparable Performance in a Macroepidemiologic Study of Staphylococcus aureus in the United States.

    Science.gov (United States)

    O'Hara, F Patrick; Suaya, Jose A; Ray, G Thomas; Baxter, Roger; Brown, Megan L; Mera, Robertino M; Close, Nicole M; Thomas, Elizabeth; Amrine-Madsen, Heather

    2016-01-01

    A number of molecular typing methods have been developed for characterization of Staphylococcus aureus isolates. The utility of these systems depends on the nature of the investigation for which they are used. We compared two commonly used methods of molecular typing, multilocus sequence typing (MLST) (and its clustering algorithm, Based Upon Related Sequence Type [BURST]) with the staphylococcal protein A (spa) typing (and its clustering algorithm, Based Upon Repeat Pattern [BURP]), to assess the utility of these methods for macroepidemiology and evolutionary studies of S. aureus in the United States. We typed a total of 366 clinical isolates of S. aureus by these methods and evaluated indices of diversity and concordance values. Our results show that, when combined with the BURP clustering algorithm to delineate clonal lineages, spa typing produces results that are highly comparable with those produced by MLST/BURST. Therefore, spa typing is appropriate for use in macroepidemiology and evolutionary studies and, given its lower implementation cost, this method appears to be more efficient. The findings are robust and are consistent across different settings, patient ages, and specimen sources. Our results also support a model in which the methicillin-resistant S. aureus (MRSA) population in the United States comprises two major lineages (USA300 and USA100), which each consist of closely related variants.

  20. Concrete Types for TypeScript

    OpenAIRE

    Richards, Gregor; Zappa Nardelli, Francesco; Vitek, Jan

    2015-01-01

    Typescript extends JavaScript with optional type annotations that are, by design, unsound and, that the Typescript compiler discards as it emits code. This design point preserves programming idioms developers are familiar with, and allows them to leave their legacy code unchanged, while offering a measure of static error checking in parts of the program that have type annotations. We present an alternative design for TypeScript, one where it is possible to support the same degree of dynamism,...

  1. Treatment of nonneovascular idiopathic macular telangiectasia type 2 with intravitreal ranibizumab: results of a phase II clinical trial.

    Science.gov (United States)

    Toy, Brian C; Koo, Euna; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

    2012-05-01

    To evaluate the safety and preliminary efficacy of intravitreal ranibizumab for nonneovascular idiopathic macular telangiectasia Type 2. Single-center, open-label Phase II clinical trial enrolling five participants with bilateral nonneovascular idiopathic macular telangiectasia Type 2. Intravitreal ranibizumab (0.5 mg) was administered every 4 weeks in the study eye for 12 months with the contralateral eye observed. Outcome measures included changes in best-corrected visual acuity, area of late-phase leakage on fluorescein angiography, and retinal thickness on optical coherence tomography. The study treatment was well tolerated and associated with few adverse events. Change in best-corrected visual acuity at 12 months was not significantly different between treated study eyes (0.0 ± 7.5 letters) and control fellow eyes (+2.2 ± 1.9 letters). However, decreases in the area of late-phase fluorescein angiography leakage (-33 ± 20% for study eyes, +1 ± 8% for fellow eyes) and in optical coherence tomography central subfield retinal thickness (-11.7 ± 7.0% for study eyes and -2.9 ± 3.5% for fellow eyes) were greater in study eyes compared with fellow eyes. Despite significant anatomical responses to treatment, functional improvement in visual acuity was not detected. Intravitreal ranibizumab administered monthly over a time course of 12 months is unlikely to provide a general and significant benefit to patients with nonneovascular idiopathic macular telangiectasia Type 2.

  2. Effects of benchmarking on the quality of type 2 diabetes care: results of the OPTIMISE (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment) study in Greece

    Science.gov (United States)

    Tsimihodimos, Vasilis; Kostapanos, Michael S.; Moulis, Alexandros; Nikas, Nikos; Elisaf, Moses S.

    2015-01-01

    Objectives: To investigate the effect of benchmarking on the quality of type 2 diabetes (T2DM) care in Greece. Methods: The OPTIMISE (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment) study [ClinicalTrials.gov identifier: NCT00681850] was an international multicenter, prospective cohort study. It included physicians randomized 3:1 to either receive benchmarking for glycated hemoglobin (HbA1c), systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) treatment targets (benchmarking group) or not (control group). The proportions of patients achieving the targets of the above-mentioned parameters were compared between groups after 12 months of treatment. Also, the proportions of patients achieving those targets at 12 months were compared with baseline in the benchmarking group. Results: In the Greek region, the OPTIMISE study included 797 adults with T2DM (570 in the benchmarking group). At month 12 the proportion of patients within the predefined targets for SBP and LDL-C was greater in the benchmarking compared with the control group (50.6 versus 35.8%, and 45.3 versus 36.1%, respectively). However, these differences were not statistically significant. No difference between groups was noted in the percentage of patients achieving the predefined target for HbA1c. At month 12 the increase in the percentage of patients achieving all three targets was greater in the benchmarking (5.9–15.0%) than in the control group (2.7–8.1%). In the benchmarking group more patients were on target regarding SBP (50.6% versus 29.8%), LDL-C (45.3% versus 31.3%) and HbA1c (63.8% versus 51.2%) at 12 months compared with baseline (p Benchmarking may comprise a promising tool for improving the quality of T2DM care. Nevertheless, target achievement rates of each, and of all three, quality indicators were suboptimal, indicating there are still unmet needs in the management of T2DM. PMID:26445642

  3. Tobacco Use, Insulin Resistance, and Risk of Type 2 Diabetes: Results from the Multi-Ethnic Study of Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Rachel J Keith

    Full Text Available Tobacco use is associated with insulin resistance and incident diabetes. Given the racial/ethnic differences in smoking patterns and incident type 2 diabetes our objective was to evaluate the association between tobacco use and insulin resistance (IR as well as incident type 2 diabetes mellitus in a contemporary multiethnic cohort.We studied 5,931 Multi- Ethnic Study of Atherosclerosis (MESA participants who at baseline were free of type 2 diabetes (fasting glucose ≥7.0 mmol/l (126 mg/dl and/or use of insulin or oral hypoglycemic medications categorized by self-reported tobacco status and reclassified by urinary cotinine (available in 58% of participants as never, current or former tobacco users. The association between tobacco use, IR (fasting plasma glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR and incident diabetes over 10 years was evaluated using multivariable linear regression and Cox proportional hazards models, respectively. Mean age of the participants was 62 (±10 years, 46% were male, 41% Caucasian, 12% Chinese, 26% African American and 21% Hispanic/Latino. IR biomarkers did not significantly differ between current, former, and never cigarette users (P >0.10 but showed limited unadjusted differences for users of cigar, pipe and smokeless tobacco (All P <0.05. Fully adjusted models showed no association between dose or intensity of tobacco exposure and any index of IR. When stratified into participants that quit smoking vs. those who continued smoking during the 10-year study there was no difference in serum glucose levels or frequency of diabetes. In fully adjusted models, there was no significant difference in diabetes risk between former or current cigarette smokers compared to never smokers [HR (95% CI 1.02 (0.77,1.37 and 0.81 (0.52,1.26 respectively].In a contemporary multi-ethnic cohort, there was no independent association between tobacco use and IR or incident type 2 diabetes. The role

  4. Comparison of imaging properties of direct-type and indirect-type of flat-panel detector

    International Nuclear Information System (INIS)

    Matsumoto, Masao; Suekane, Koji; Ichimaru, Yasunobu; Ogata, Yuji; Inamura, Kiyonari; Kanai, Kouzou; Kanamori, Hitoshi

    2002-01-01

    A Flat-Panel Detector (FPD) has many advantages such as eliminating cassette handling and being able to display a preview image immediately in addition to the digital image processing and the networking. Thus, the FPD has ability to innovate the radiology department. We measured and evaluated the digital and over-all imaging properties (characteristic curves, modulation Transfer Functions, Wiener spectra and Noise Equivalent Quanta (NEQ) for the direct-type and indirect-type of FPD. The pre-sampling and overall NEQ of the indirect-type of FPD were better than the NEQ of the direct-type of FPD at lower spatial frequencies, but were worse at higher spatial frequencies. The FPD can take image data at real-time and be easy to digitalize. From these results, Screen/Film system and Computed Radiography system will be replaced by the FPD system, together with diffusion of CAD, cone beam Computed Tomography (CT) system and open-type Magnetic Resonance Imagining (MRI) system. (T. Tanaka)

  5. Sensitivity analysis of reflector types and impurities in 10 MW MTR type nuclear research reactor

    International Nuclear Information System (INIS)

    Khattab, K.; Khamis, I.

    2007-01-01

    The 2-D and 3-D neutronics models for 10 MW nuclear research reactor of MTR type have been developed and presented in this paper. Our results agree very well with the results of seven countries mentioned in the IAEA-TECDOC-233. To study the effect of reflector types on the reactor effective multiplication factor, five types of reflectors such as pure beryllium, beryllium, heavy water, carbon and water are selected for this study. The pure beryllium is found to be the most efficient reflector in this group. The effect of the most important impurities, which exist on the beryllium reflector such as iron, silicon and aluminium on the reactor multiplication factor, have been analyzed as well. It is found that the iron impurity affects the reactor multiplication factor the most compared to silicon and aluminium impurities. (author)

  6. Comparability of Results between Point-of-Care and Automated Instruments to Measure B-type Natriuretic Peptide

    OpenAIRE

    Shah, Kevin; Terracciano, Garrett J.; Jiang, Kevin; Maisel, Alan S.; Fitzgerald, Robert L.

    2010-01-01

    Objectives: Heart failure is one of the leading causes of death in the U.S. The incorporation of B-type natriuretic peptide (BNP) measurements when triaging patients presenting with shortness of breath has improved the diagnostic and prognostic ability of physicians. Currently, there are no point-of-care systems for quantifying BNP that can be used without sacrificing accuracy. We compared the analytical performance of the Abbott i-STAT analyzer, a handheld point-of-care system for measuring ...

  7. Herpes simplex virus type 2 seropositivity among urban adults in Africa - Results from two cross-sectional surveys in Addis Ababa, Ethiopia

    NARCIS (Netherlands)

    Mihret, Wude; Rinke de Wit, Tobias F.; Petros, Beyene; Mekonnen, Yared; Tsegaye, Aster; Wolday, Dawit; Beyene, Asfaw; Aklilu, Mathias; Sanders, Eduard; Fontanet, Arnaud L.

    2002-01-01

    BACKGROUND: Although several surveys investigating the epidemiology of herpes simplex virus type 2 (HSV-2) infection using type-specific immunologic assays have been carried out in Africa, none has examined the risk factors for HSV-2 infection in a representative sample from an urban adult

  8. Multifluid Block-Adaptive-Tree Solar Wind Roe-Type Upwind Scheme: Magnetospheric Composition and Dynamics During Geomagnetic Storms-Initial Results

    Science.gov (United States)

    Glocer, A.; Toth, G.; Ma, Y.; Gombosi, T.; Zhang, J.-C.; Kistler, L. M.

    2009-01-01

    The magnetosphere contains a significant amount of ionospheric O+, particularly during geomagnetically active times. The presence of ionospheric plasma in the magnetosphere has a notable impact on magnetospheric composition and processes. We present a new multifluid MHD version of the Block-Adaptive-Tree Solar wind Roe-type Upwind Scheme model of the magnetosphere to track the fate and consequences of ionospheric outflow. The multifluid MHD equations are presented as are the novel techniques for overcoming the formidable challenges associated with solving them. Our new model is then applied to the May 4, 1998 and March 31, 2001 geomagnetic storms. The results are juxtaposed with traditional single-fluid MHD and multispecies MHD simulations from a previous study, thereby allowing us to assess the benefits of using a more complex model with additional physics. We find that our multifluid MHD model (with outflow) gives comparable results to the multispecies MHD model (with outflow), including a more strongly negative Dst, reduced CPCP, and a drastically improved magnetic field at geosynchronous orbit, as compared to single-fluid MHD with no outflow. Significant differences in composition and magnetic field are found between the multispecies and multifluid approach further away from the Earth. We further demonstrate the ability to explore pressure and bulk velocity differences between H+ and O+, which is not possible when utilizing the other techniques considered

  9. Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC.

    Science.gov (United States)

    Lenherr, Sara M; Clemens, J Quentin; Braffett, Barbara H; Cleary, Patricia A; Dunn, Rodney L; Hotaling, James M; Jacobson, Alan M; Kim, Catherine; Herman, William; Brown, Jeanette S; Wessells, Hunter; Sarma, Aruna V

    2016-10-01

    We examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus. Women enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model. A total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy. The frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Molecular Typing of Neisseria gonorrhoeae Isolates by Opa-Typing and Ribotyping in New Delhi, India

    Directory of Open Access Journals (Sweden)

    Pejvak Khaki

    2009-01-01

    Full Text Available Control and preventive measures for gonococcal infections are based on precise epidemiological characteristics of N. gonorrhoeae isolates. In the present study the potential utility of opa-typing and ribotyping for molecular epidemiological study of consecutive gonococcal strains was determined. Sixty gonococcal isolates were subjected to ribotyping with two restriction enzymes, AvaII and HincII, and opa-typing with TaqI and HpaII for epidemiological characterization of gonococcal population. Ribotyping with AvaII yielded 6 ribotype patterns while twelve RFLP patterns were observed with HincII. Opa-typing of the 60 isolates revealed a total 54 opa-types, which 48 were unique and 6 formed clusters. Fifty-two opa-types were observed with TaqI-digested PCR product while opa-typing with HpaII demonstrated 54 opa-types. The opa-types from isolates that were epidemiologically unrelated were distinct, whereas those from the sexual contacts were identical. The results showed that opa-typing is highly useful for characterizing gonococcal strains from sexual contacts and has more discriminatory than ribotyping that could differentiate between gonococci of the same ribotype. The technique even with a single restriction enzyme has a high level of discrimination (99.9% between epidemiologically unrelated isolates. In conclusion, the molecular methods such as opa-typing and ribotyping can be used for epidemiological characterization of gonococcal strains.

  11. Molecular Typing of Neisseria gonorrhoeae Isolates by Opa-Typing and Ribotyping in New Delhi, India

    Science.gov (United States)

    Khaki, Pejvak; Bhalla, Preena; Fayaz, Ahmad Mir; Moradi Bidhendi, Sohiela; Esmailzadeh, Majid; Sharma, Pawan

    2009-01-01

    Control and preventive measures for gonococcal infections are based on precise epidemiological characteristics of N. gonorrhoeae isolates. In the present study the potential utility of opa-typing and ribotyping for molecular epidemiological study of consecutive gonococcal strains was determined. Sixty gonococcal isolates were subjected to ribotyping with two restriction enzymes, AvaII and HincII, and opa-typing with TaqI and HpaII for epidemiological characterization of gonococcal population. Ribotyping with AvaII yielded 6 ribotype patterns while twelve RFLP patterns were observed with HincII. Opa-typing of the 60 isolates revealed a total 54 opa-types, which 48 were unique and 6 formed clusters. Fifty-two opa-types were observed with TaqI-digested PCR product while opa-typing with HpaII demonstrated 54 opa-types. The opa-types from isolates that were epidemiologically unrelated were distinct, whereas those from the sexual contacts were identical. The results showed that opa-typing is highly useful for characterizing gonococcal strains from sexual contacts and has more discriminatory than ribotyping that could differentiate between gonococci of the same ribotype. The technique even with a single restriction enzyme has a high level of discrimination (99.9%) between epidemiologically unrelated isolates. In conclusion, the molecular methods such as opa-typing and ribotyping can be used for epidemiological characterization of gonococcal strains. PMID:20016674

  12. Population-based incidence of Type 2 diabetes and its associated risk factors: results from a six-year cohort study in Iran

    Directory of Open Access Journals (Sweden)

    Saadat Navid

    2009-06-01

    Full Text Available Abstract Background The Middle East is estimated to have the largest increase in prevalence of diabetes by 2030; yet there is lack of published data on the incidence of Type 2 diabetes in this region. This study aimed to estimate Type 2 diabetes incidence and its associated risk factors in an Iranian urban population. Methods Among 3307 non-diabetics ≥ 20 years (mean age 42 ± 13 years, 42% males, glucose tolerance test was performed at baseline in 1999–2001 and at two consecutive phases in 2001–2005 and 2005–2008. Diabetes and glucose tolerance status were defined according to the ADA 1997 criteria. Logistic regression was used to determine the independent variables associated with incident diabetes and their odds ratios (OR. Results After median follow-up of 6 years, 237 new cases of diabetes were ascertained corresponding to an age and sex standardized cumulative incidence of 6.4% (95%CI: 5.6–7.2 and incidence rate of 10.6 (9.2–12.1 per 1000 person years. Besides classical diabetes risk factors, female sex and low education level significantly increased risk of diabetes in age adjusted models. In full model, the independent predictors were age [OR, 95%CI: 1.2 (1.1–1.3], family history of diabetes [1.8 (1.3–2.5], body mass index ≥ 30 kg/m2 [2.3 (1.5–3.6], abdominal obesity [1.9 (1.4–2.6], high triglyceride [1.4 (1.1–1.9], Isolated impaired fasting glucose (IFG [7.4 (3.6–15.0], Isolated impaired glucose tolerance (IGT [5.9 (4.2–8.4] and combined IFG and IGT [42.2 (23.8–74.9]. Conclusion More than 1% of the Iranian urban population older than 20 years develops Type 2 diabetes each year. Combination of IFG and IGT was the strongest predictor of incident diabetes among the modifiable risk factors.

  13. Type 1 narcolepsy

    DEFF Research Database (Denmark)

    Degn, Matilda; Kornum, Birgitte Rahbek

    2015-01-01

    Type 1 narcolepsy is a sleep disorder characterized by excessive daytime sleepiness with unintentional sleep attacks and cataplexy. The disorder is caused by a loss of hypocretinergic neurons in the brain. The specific loss of these neurons in narcolepsy is thought to result from an autoimmune...

  14. Search Results | Page 15 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Results 141 - 150 of 650 ... Filter by type .... Protecting Privacy in the Global South (Phase 2) ... are at a high risk of getting type 2 diabetes sometime after their pregnancy. ... The project team will review the literature on how women's economic ...

  15. Type A and type behaviors and factors related to job satisfaction among male white-collar workers.

    Science.gov (United States)

    Hagihara, A; Tarumi, K; Morimoto, K

    1998-01-01

    Numerous studies have examined the health effects of Type A behavior and job satisfaction/dissatisfaction, but we know very little about the relationship between aspects of the work environment related to job satisfaction and the Type A behavior pattern. In the present study, we analyzed data concerning work Stressors, private aspects of life, and job satisfaction among male white-collar workers (n=657) in a large steel company, and identified the respective aspects of the work environment related to job satisfaction among groups divided by Type A/B behavior patterns.We found that the nature of predictors for job satisfaction varied with the behavior type. "Being not busy at work" (pjob satisfaction among the Type A workers while "working less than 10 hours per day" (pjob satisfaction among the Type workers. "Work performance is evaluated" was a significant predictor of job satisfaction among all three behavior types (A, B, and A/B).Our results can provide information useful for the creation of programs to lower the level of job dissatisfaction and mental stress depending upon the behavior type of employees.

  16. Achieving ADA/ISPAD clinical guideline goals is associated with higher insulin sensitivity and cardiopulmonary fitness in adolescents with type 1 diabetes: Results from RESistance to InSulin in Type 1 ANd Type 2 diabetes (RESISTANT) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with Type 1 Diabetes (EMERALD) Studies.

    Science.gov (United States)

    Bjornstad, Petter; Cree-Green, Melanie; Baumgartner, Amy; Coe, Gregory; Reyes, Yesenia Garcia; Schäfer, Michal; Pyle, Laura; Regensteiner, Judith G; Reusch, Jane Eb; Nadeau, Kristen J

    2018-05-01

    Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement would be associated with better insulin sensitivity (IS) and cardiopulmonary fitness. IS was quantified as glucose infusion rate (GIR) from a hyperinsulinemic-euglycemic clamp in youth with type 1 diabetes from the RESistance to InSulin in Type 1 ANd Type 2 diabetes (RESISTANT) (n = 86) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with Type 1 Diabetes (EMERALD) (n = 41) cohorts (n = 127; age 15.7 ± 2.2 years, 52% girls). Cardiopulmonary fitness was measured as peak oxygen consumption (VO 2 peak/kg) during upright (RESISTANT) or supine (EMERALD) cycle ergometry and were stratified by cycle type. Goal achievement was defined as HbA1c 35 mg/dL, triglycerides ADA/ISPAD goal achievement was associated with greater IS and cardiopulmonary fitness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. [Surgery for diabetes type 2?].

    Science.gov (United States)

    Müller, Markus K; Nocito, A; Schiesser, M

    2010-02-17

    Diabetes mellitus type 2 is a chronic disease with increasing prevalence in western society. Obesity represents a well established risk factor for the development of diabetes mellitus type 2. Several studies on surgical procedures for the treatment of obesity have shown a postoperative reduction of obesity-related co-morbidities. Thus, diabetes mellitus type 2 was shown to resolve or improve in more than 75% of morbidly obese patients (BMI >35) after bariatric surgery. These insights paved the way for the advent of metabolic surgery - a novel field with the goal to improve glucose metabolism in patients with a BMI of less than 35. Encouraging results from mostly observational studies have sparked the interest in the surgical management of diabetes mellitus type 2.

  18. Associations between stress and migraine and tension-type headache: Results from a school-based study in adolescents from grammar schools in Germany

    OpenAIRE

    Milde-Busch, Astrid; Blaschek, Astrid; Heinen, Florian; Borggräfe, Ingo; Koerte, Inga; Straube, Andreas; Schankin, Christoph; Kries, Rüdiger

    2011-01-01

    Introduction: Stress is considered the major contributor to migraine and tension-type headache in adolescents. Previous studies have focused on general stressors, whereas the aim of the present study was to investigate associations between individuals’ stressful experiences and different types of headache. Methods: Adolescents from 10th and 11th grades of grammar schools filled in questionnaires. Stressful experiences were measured with the Trier Inventory of Chronic Stress. Type of heada...

  19. The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

    Science.gov (United States)

    Stubbe, Beate; Schipf, Sabine; Schäper, Christoph; Felix, Stephan B; Steveling, Antje; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Friedrich, Nele; Ewert, Ralf; Ittermann, Till; Gläser, Sven

    2017-01-01

    Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Development of Independent-type Optical CT

    Science.gov (United States)

    Yamaguchi, Tatsushi; Shiozawa, Daigoro; Rokunohe, Toshiaki; Kida, Junzo; Zhang, Wei

    Optical current transformers (optical CTs) have features that they can be made much smaller and lighter than conventional electromagnetic induction transformers by their simple structure, and contribute to improvement of equipment reliability because of their excellent surge resistance performance. Authors consider optical CTs to be next generation transformers, and are conducting research and development of optical CTs aiming to apply to measuring and protection in electric power systems. Specifically we developed an independent-type optical CT by utilizing basic data of optical CTs accumulated for large current characteristics, temperature characteristics, vibration resistance characteristics, and so on. In performance verification, type tests complying with IEC standards, such as short-time current tests, insulation tests, accuracy tests, and so on, showed good results. This report describes basic principle and configuration of optical CTs. After that, as basic characteristics of optical CTs, conditions and results of verification tests for dielectric breakdown characteristics of sensor fibers, large current characteristics, temperature characteristics, and vibration resistance characteristics are described. Finally, development outline of the independent-type optical CT aiming to apply to all digital substation and its type tests results are described.

  1. Comparison of osteoporosis in US adults with type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    DeShields, S C; Cunningham, T D

    2018-01-20

    We examined bone mineral density (BMD) and osteoporosis prevalence in those with type 1 compared to type 2 diabetes derived from a nationally representative sample from the civilian community in the United States. Data from the National Health and Nutrition Examination Survey (NHANES) for 2005-2006, 2007-2008, 2009-2010, and 2013-2014 were merged to obtain a large sample of diabetics at least 20 years of age with participation in the interview and medical examination. Osteoporosis status was defined by BMD at the total femur, femoral neck, or total lumbar spine. Self-reported diabetics that were prescribed insulin within the first year of diagnosis, are currently taking insulin, and reported no prescriptions for any diabetic pills were classified as type 1. Remaining self-reported diabetics were deemed as having type 2. A total of 2050 diabetics were included in which 87 (4%) were classified as type 1. Type 1 diabetics were found to have a significantly lower BMD at the total femur and femoral neck, but not at the lumbar spine in the adjusted models. Diabetics with type 1 were 4.7 times more likely to have osteoporosis than those with type 2. There was no significant relationship between diabetes type and BMD or osteoporosis prior to adjustment for confounders. Although our results show an increased likelihood of osteoporosis among those with type 1 diabetes, future studies including a larger sample from a community population are needed. It may benefit diabetics, especially those with type 1, to initiate osteoporosis screening methods including evaluation of fracture risk, bone quality, and BMD measurements at multiple sites earlier than recommended.

  2. Semi-Discrete Ingham-Type Inequalities

    International Nuclear Information System (INIS)

    Komornik, Vilmos; Loreti, Paola

    2007-01-01

    One of the general methods in linear control theory is based on harmonic and non-harmonic Fourier series. The key of this approach is the establishment of various suitable adaptations and generalizations of the classical Parseval equality. A new and systematic approach was begun in our papers in collaboration with Baiocchi. Many recent results of this kind, obtained through various Ingham-type theorems, were exposed recently. Although this work concentrated on continuous models, in connection with numerical simulations a natural question is whether these results also admit useful discrete versions. The purpose of this paper is to establish discrete versions of various Ingham-type theorems by using our approach. They imply the earlier continuous results by a simple limit process

  3. Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis.

    Science.gov (United States)

    Mirza, Eraj Humayun; Pan-Pan, Chong; Wan Ibrahim, Wan Mohd Azhar Bin; Djordjevic, Ivan; Pingguan-Murphy, Belinda

    2015-11-01

    Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2 ) and hypoxia (5% O2 ). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture. Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic environment. © 2015 Wiley Periodicals, Inc.

  4. Matrilin-3 chondrodysplasia mutations cause attenuated chondrogenesis, premature hypertrophy and aberrant response to TGF-β in chondroprogenitor cells.

    Science.gov (United States)

    Jayasuriya, Chathuraka T; Zhou, Fiona H; Pei, Ming; Wang, Zhengke; Lemme, Nicholas J; Haines, Paul; Chen, Qian

    2014-08-21

    Studies have shown that mutations in the matrilin-3 gene (MATN3) are associated with multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT) MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-β treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-β. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-β treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy.

  5. Matrilin-3 Chondrodysplasia Mutations Cause Attenuated Chondrogenesis, Premature Hypertrophy and Aberrant Response to TGF-β in Chondroprogenitor Cells

    Directory of Open Access Journals (Sweden)

    Chathuraka T. Jayasuriya

    2014-08-01

    Full Text Available Studies have shown that mutations in the matrilin-3 gene (MATN3 are associated with multiple epiphyseal dysplasia (MED and spondyloepimetaphyseal dysplasia (SEMD. We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-β treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-β. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-β treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy.

  6. High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.

    Science.gov (United States)

    Sato, Eiichi; Ando, Takashi; Ichikawa, Jiro; Okita, Genki; Sato, Nobutaka; Wako, Masanori; Ohba, Tetsuro; Ochiai, Satoshi; Hagino, Tetsuo; Jacobson, Richard; Haro, Hirotaka

    2014-12-01

    Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

    Science.gov (United States)

    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  8. Types and Forms of Tourism

    Directory of Open Access Journals (Sweden)

    Anca Gabriela Turtureanu

    2008-10-01

    Full Text Available For the study of tourism, the most suitable method from the geographic point of view is typify it, because it allows the delimitation oftourist areas. Tourist areas are characterized by a specific type of travel or by a reunion of some types that may vary dynamically over time. Thetypes of tourism result mainly from the different motivations of the journey, i.e. the purpose of doing. Each type of tourism is distinguished by suchspecific purpose and it is specific to those regions where fixed purpose can be achieved by the existence of some specific facilities.

  9. THE ENVIRONMENTAL DEPENDENCE OF THE FRACTION OF 'UNCONVENTIONAL' GALAXIES: RED LATE TYPES AND BLUE EARLY TYPES

    International Nuclear Information System (INIS)

    Deng Xinfa; He Jizhou; Wu Ping; Ding Yingping

    2009-01-01

    From the Main galaxy sample of the Sloan Digital Sky Survey Data Release 6, we construct two volume-limited samples with the luminosity -20.0 ≤ M r ≤ -18.5 and -22.40 ≤ M r ≤ -20.16, respectively, to explore the environmental dependence of the fraction of 'unconventional' galaxies: red late types and blue early types. We use the density estimator within the distance to the fifth nearest neighbor, and construct two samples at both extremes of density and perform comparative studies between them for each volume-limited sample. Results of two volume-limited samples show the same conclusions: the fraction of red late-type galaxies rises considerably with increasing local density, and that one of the blue early-type galaxies declines substantially with increasing local density. In addition, we note that bluer galaxies preferentially are late types, but the red galaxies are not dominated by early types.

  10. Does emotional stress cause type 2 diabetes mellitus?

    DEFF Research Database (Denmark)

    Pouwer, Frans; Kupper, Nina; Adriaanse, Marcel C

    2010-01-01

    and the development of type 2 diabetes mellitus. Results of longitudinal studies suggest that not only depression but also general emotional stress and anxiety, sleeping problems, anger, and hostility are associated with an increased risk for the development of type 2 diabetes. Conflicting results were found......According to the World Health Organization, approximately 220 million people worldwide have type 2 diabetes mellitus. Patients with type 2 diabetes not only have a chronic disease to cope with, they are also at increased risk for coronary heart disease, peripheral vascular disease, retinopathy......, nephropathy, and neuropathy. The exact causes of type 2 diabetes are still not clear. Since the 17th century, it has been suggested that emotional stress plays a role in the etiology of type 2 diabetes mellitus. So far, review studies have mainly focused on depression as a risk factor for the development...

  11. Development of remote controlled type field-emission type scanning electron microscope

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, Ryo; Nishino, Yasuharu; Mita, Naoaki; Nakata, Masahito; Harada, Katsuya; Nozawa, Yukio; Amano, Hidetoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-10-01

    The extending burn-up of Light Water Reactor Fuels has been promoted to reduce costs of the power generation and amount of waste mass. Information about the fuel behavior under high burn-up operation is needed to assess safety of the high burn-up fuels. Microstructures formed in high burn-up fuel pellets and Zircaloy tubes influence on their integrity. The fundamental information about morphology, sizes, and element compositions in those microstructures is necessary to estimate the formation mechanism and change in the properties of the fuels. The Field Emission type Scanning Electron Microscope (FE-SEM), which is effective for observation of very small area, i.e., nano-size structures, has been hence installed at the Reactor Fuel Examination Facility (RFEF) in JAERI. FE-SEM is designed for the remote handling type to use high radioactive materials and has equipments to keep the safety for operators. The Energy Dispersive Spectrometer (EDS) with a radiation-shielding collimator has been also equipped on FE-SEM to determine element compositions in the structures. Characterization tests were carried out using Zircaloy cladding tubes with oxide films and hydrides of confirm machine performance. In the results of the tests, high-resolution images with a magnification of 30,000 were obtained. Those results show that the apparatus maintains the original high performance with standard type. (author)

  12. Study of type III ELMs in JET

    NARCIS (Netherlands)

    Sartori, R.; Saibene, G.; Horton, L. D.; Becoulet, M.; Budny, R.; Borba, D.; Chankin, A.; Conway, G. D.; Cordey, G.; McDonald, D.; Guenther, K.; von Hellermann, M. G.; Igithkanov, Y.; Loarte, A.; Lomas, P. J.; Pogutse, O.; Rapp, J.

    2004-01-01

    This paper presents the results of JET experiments aimed at studying the operational space of plasmas with a Type III ELMy edge, in terms of both local and global plasma parameters. In JET, the Type III ELMy regime has a wide operational space in the pedestal n(e)-T-e diagram, and Type III ELMs are

  13. Study of araldite in edge protection of n-type and p-type surface barrier detectors

    International Nuclear Information System (INIS)

    Alencar, M.A.V.; Jesus, E.F.O.; Lopes, R.T.

    1995-01-01

    The aim of this work is the realization of a comparative study between the surface barrier detectors performance n and type using the epoxy resin Araldite as edge protection material with the purpose of determining which type of detector (n or p) the use of Araldite is more indicated. The surface barrier detectors were constructed using n and p type silicon wafer with resistivity of 3350Ω.cm and 5850 Ω.cm respectively. In the n type detectors, the metals used as ohmic and rectifier contacts were the Al and Au respectively, while in the p type detectors, the ohmic and rectifier contacts were Au and Al. All metallic contacts were done by evaporation in high vacuum (∼10 -4 Torr) and with deposit of 40 μm/cm 2 . The obtained results for the detectors (reverse current of -350nA and resolution from 21 to 26 keV for p type detectors and reserve current of 1μA and resolution from 44 to 49 keV for n type detectors) tend to demonstrate that use of epoxy resin Araldite in the edge protection is more indicated to p type surface barrier detectors. (author). 3 refs., 4 figs., 1 tab

  14. When Do Types Induce the Same Belief Hierarchy?

    Directory of Open Access Journals (Sweden)

    Andrés Perea

    2016-10-01

    Full Text Available Type structures are a simple device to describe higher-order beliefs. However, how can we check whether two types generate the same belief hierarchy? This paper generalizes the concept of a type morphism and shows that one type structure is contained in another if and only if the former can be mapped into the other using a generalized type morphism. Hence, every generalized type morphism is a hierarchy morphism and vice versa. Importantly, generalized type morphisms do not make reference to belief hierarchies. We use our results to characterize the conditions under which types generate the same belief hierarchy.

  15. Measuring Ambiguity in HLA Typing Methods

    Science.gov (United States)

    Madbouly, Abeer; Freeman, John; Maiers, Martin

    2012-01-01

    In hematopoietic stem cell transplantation, donor selection is based primarily on matching donor and patient HLA genes. These genes are highly polymorphic and their typing can result in exact allele assignment at each gene (the resolution at which patients and donors are matched), but it can also result in a set of ambiguous assignments, depending on the typing methodology used. To facilitate rapid identification of matched donors, registries employ statistical algorithms to infer HLA alleles from ambiguous genotypes. Linkage disequilibrium information encapsulated in haplotype frequencies is used to facilitate prediction of the most likely haplotype assignment. An HLA typing with less ambiguity produces fewer high-probability haplotypes and a more reliable prediction. We estimated ambiguity for several HLA typing methods across four continental populations using an information theory-based measure, Shannon's entropy. We used allele and haplotype frequencies to calculate entropy for different sets of 1,000 subjects with simulated HLA typing. Using allele frequencies we calculated an average entropy in Caucasians of 1.65 for serology, 1.06 for allele family level, 0.49 for a 2002-era SSO kit, and 0.076 for single-pass SBT. When using haplotype frequencies in entropy calculations, we found average entropies of 0.72 for serology, 0.73 for allele family level, 0.05 for SSO, and 0.002 for single-pass SBT. Application of haplotype frequencies further reduces HLA typing ambiguity. We also estimated expected confirmatory typing mismatch rates for simulated subjects. In a hypothetical registry with all donors typed using the same method, the entropy values based on haplotype frequencies correspond to confirmatory typing mismatch rates of 1.31% for SSO versus only 0.08% for SBT. Intermediate-resolution single-pass SBT contains the least ambiguity of the methods we evaluated and therefore the most certainty in allele prediction. The presented measure objectively evaluates HLA

  16. Measuring ambiguity in HLA typing methods.

    Directory of Open Access Journals (Sweden)

    Vanja Paunić

    Full Text Available In hematopoietic stem cell transplantation, donor selection is based primarily on matching donor and patient HLA genes. These genes are highly polymorphic and their typing can result in exact allele assignment at each gene (the resolution at which patients and donors are matched, but it can also result in a set of ambiguous assignments, depending on the typing methodology used. To facilitate rapid identification of matched donors, registries employ statistical algorithms to infer HLA alleles from ambiguous genotypes. Linkage disequilibrium information encapsulated in haplotype frequencies is used to facilitate prediction of the most likely haplotype assignment. An HLA typing with less ambiguity produces fewer high-probability haplotypes and a more reliable prediction. We estimated ambiguity for several HLA typing methods across four continental populations using an information theory-based measure, Shannon's entropy. We used allele and haplotype frequencies to calculate entropy for different sets of 1,000 subjects with simulated HLA typing. Using allele frequencies we calculated an average entropy in Caucasians of 1.65 for serology, 1.06 for allele family level, 0.49 for a 2002-era SSO kit, and 0.076 for single-pass SBT. When using haplotype frequencies in entropy calculations, we found average entropies of 0.72 for serology, 0.73 for allele family level, 0.05 for SSO, and 0.002 for single-pass SBT. Application of haplotype frequencies further reduces HLA typing ambiguity. We also estimated expected confirmatory typing mismatch rates for simulated subjects. In a hypothetical registry with all donors typed using the same method, the entropy values based on haplotype frequencies correspond to confirmatory typing mismatch rates of 1.31% for SSO versus only 0.08% for SBT. Intermediate-resolution single-pass SBT contains the least ambiguity of the methods we evaluated and therefore the most certainty in allele prediction. The presented measure

  17. Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis.

    NARCIS (Netherlands)

    Laar, F.A. van de; Lucassen, P.L.B.J.; Akkermans, R.P.; Lisdonk, E.H. van de; Rutten, G.E.H.M.; Weel, C. van

    2005-01-01

    OBJECTIVE: To review the effects of monotherapy with alpha-glucosidase inhibitors (AGIs) for patients with type 2 diabetes, with respect to mortality, morbidity, glycemic control, insulin levels, plasma lipids, body weight, and side effects. RESEARCH DESIGN AND METHODS: We systematically searched

  18. Moderne behandling af type B-aortadissektion

    DEFF Research Database (Denmark)

    Klitfod, L.; Baekgaard, N.; Just, S.

    2008-01-01

    Rapid classification is essential in the management of aortic dissections, as Type A dissections require surgery, while the optimal treatment of Type B dissections is controversial. Medical treatment with antihypertensive medication and analgesics has so far been the main treatment of uncomplicated...... Type B dissections, while surgery has been reserved for complications and persistent pain in spite of medical treatment. Endovascular techniques are less invasive than open repair and show promising early results Udgivelsesdato: 2008/9/8...

  19. [Modern treatment of type B dissections

    DEFF Research Database (Denmark)

    Klitfod, L.; Baekgaard, N.; Just, S.

    2008-01-01

    Rapid classification is essential in the management of aortic dissections, as Type A dissections require surgery, while the optimal treatment of Type B dissections is controversial. Medical treatment with antihypertensive medication and analgesics has so far been the main treatment of uncomplicated...... Type B dissections, while surgery has been reserved for complications and persistent pain in spite of medical treatment. Endovascular techniques are less invasive than open repair and show promising early results Udgivelsesdato: 2008/9/8...

  20. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study).

    Science.gov (United States)

    Rådholm, Karin; Figtree, Gemma; Perkovic, Vlado; Solomon, Scott D; Mahaffey, Kenneth W; de Zeeuw, Dick; Fulcher, Greg; Barrett, Terrance D; Shaw, Wayne; Desai, Mehul; Matthews, David R; Neal, Bruce

    2018-03-11

    BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure and cardiovascular death overall, in those with and without a baseline history of heart failure, and in other participant subgroups. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized heart failure. RESULTS : Participants with a history of heart failure at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P failure was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized heart failure (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized heart failure alone (HR, 0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized heart failure may be greater in patients with a prior history of heart failure (HR, 0.61; 95% CI, 0.46-0.80) compared with those without heart failure at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without heart failure at baseline (all interaction P values >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of heart failure ( P =0.03). CONCLUSIONS : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized heart

  1. Experimental studies of minienvironment types

    International Nuclear Information System (INIS)

    Eissler, W.; Schneider, H.

    1994-01-01

    Various minienvironment types are available offering different features at quite different costs. MEISSNER+WURST performed in its JESSI project experimental tests to examine the isolation capabilities and the recovery time of minienvironments and the influence of manual handling and maintenance on the minienvironment cleanliness. An isolation factor up to 1 million was measured in the experiments. The Custom Tailored Minienvironment has the best protection against external and internal particle sources. Critical points in the design and the installation of minienvironments were identified. The results of air flow visualization studies were confirmed by airflow simulations. The result of the studies allow a classification of minienvironment types according to their cleanliness achievements

  2. STAR-TYPE LOCAL AREA NETWORK ACCESS CONTROL

    Institute of Scientific and Technical Information of China (English)

    逯昭义; 齐藤忠夫

    1990-01-01

    The multiple access fashion is a new resolution for the star-type local area network (LAN) access control and star-type optical fibre LAN. Arguments about this network are discussed, and the results are introduced.

  3. Spectrophotometry of VV Cephei-type systems

    International Nuclear Information System (INIS)

    Piccirillo, J.

    1974-01-01

    Photoelectric spectrophotometry of four VV Cephei-type systems and two related objects is analyzed to derive the visual magnitude differences of the binary components. The results are in good agreement with previous photometric determinations. An extension of the present technique to other types of binary systems is briefly discussed. (U.S.)

  4. DiAlert: a prevention program for overweight first degree relatives of type 2 diabetes patients: results of a pilot study to test feasibility and acceptability

    Directory of Open Access Journals (Sweden)

    Heideman Wieke H

    2012-09-01

    Full Text Available Abstract Background Prevalence of type 2 diabetes mellitus is increasing due to lifestyle changes, particularly affecting those genetically at risk. We developed DiAlert as a targeted group-based intervention aimed to promote intrinsic motivation and action planning for lifestyle changes and weight loss in first degree relatives of patients with type 2 diabetes mellitus. The main objective of the pilot of the DiAlert intervention was to assess fidelity, feasibility and acceptability prior to starting the randomized controlled trial. Methods Individuals with a family history of type 2 diabetes mellitus were self-identified and screened for eligibility. DiAlert consists of two group sessions. Feasibility, fidelity, acceptability and self-reported perceptions and behavioral determinants were evaluated in a pre-post study using questionnaires and observations. Determinants of behavior change were analyzed using paired-samples t tests and Wilcoxon signed rank tests. Results DiAlert was delivered to two groups of first degree relatives of patients with type 2 diabetes mellitus (N = 9 and N = 12. Feasibility and fidelity were confirmed. Overall, the DiAlert group sessions were positively evaluated (8.0 on a scale of 1 to 10 by participants. The intervention did not impact perceived susceptibility or worry about personal diabetes risk. Action planning with regard to changing diet and physical activity increased. Conclusions DiAlert proved feasible and was well-accepted by participants. Positive trends in action planning indicate increased likelihood of actual behavior change following DiAlert. Testing the effectiveness in a randomized controlled trial is imperative. Trial registration Netherlands National Trial Register (NTR: NTR2036

  5. Regulation of human mesenchymal stem cells differentiation into chondrocytes in extracellular matrix-based hydrogel scaffolds.

    Science.gov (United States)

    Du, Mingchun; Liang, Hui; Mou, Chenchen; Li, Xiaoran; Sun, Jie; Zhuang, Yan; Xiao, Zhifeng; Chen, Bing; Dai, Jianwu

    2014-02-01

    To induce human mesenchymal stem cells (hMSCs) to differentiate into chondrocytes in three-dimensional (3D) microenvironments, we developed porous hydrogel scaffolds using the cartilage extracellular matrix (ECM) components of chondroitin sulfate (CS) and collagen (COL). The turbidity and viscosity experiments indicated hydrogel could form through pH-triggered co-precipitation when pH=2-3. Enzyme-linked immunosorbent assay (ELISA) confirmed the hydrogel scaffolds could controllably release growth factors as envisaged. Transforming growth factor-β (TGF-β) was released to stimulate hMSCs differentiation into chondrocytes; and then collagen binding domain-basic fibroblast growth factor (CBD-bFGF) was released to improve the differentiation and preserve the chondrocyte phenotype. In in vitro cell culture experiments, the differentiation processes were compared in different microenvironments: 2D culture in culture plate as control, 3D culture in the fabricated scaffolds without growth factors (CC), the samples with CBD-bFGF (CC-C), the samples with TGF-β (CC-T), the samples with CBD-bFGF/TGF-β (CC-CT). Real-time polymerase chain reaction (RT-PCR) revealed the hMSC marker genes of CD44 and CD105 decreased; at the same time the chondrocyte marker genes of collagen type II and aggrecan increased, especially in the CC-CT sample. Immunostaining results further confirmed the hMSC marker protein of CD 44 disappeared and the chondrocyte marker protein of collagen type II emerged over time in the CC-CT sample. These results imply the ECM-based hydrogel scaffolds with growth factors can supply suitable 3D cell niches for hMSCs differentiation into chondrocytes and the differentiation process can be regulated by the controllably released growth factors. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. RhoA/Rho kinase signaling regulates transforming growth factor-β1-induced chondrogenesis and actin organization of synovium-derived mesenchymal stem cells through interaction with the Smad pathway.

    Science.gov (United States)

    Xu, Ting; Wu, Mengjie; Feng, Jianying; Lin, Xinping; Gu, Zhiyuan

    2012-11-01

    Recent studies have suggested that synovium-derived mesenchymal stem cells (SMSCs) may be promising candidates for tissue engineering and play an important role in cartilage regeneration. However, the mechanisms of SMSC chondrogenesis remain to be identified and characterized. The aim of this study was to evaluate the activation of the RhoA/Rho kinase (ROCK) pathway, as well as the manner by which it may contribute to chondrogenesis and the actin cytoskeletal organization of rat temporomandibular SMSCs in response to transforming growth factor-β1 (TGF-β1). Primary isolated SMSCs were treated with TGF-β1, and their actin organization was examined by fluorescein isothiocyanate-phalloidin staining. The specific biochemical inhibitors, C3 transferase, Y27632 and SB431542, were employed to evaluate the function of RhoA/ROCK and Smads. The effect of C3 transferase and Y27632 on the gene expression of chondrocyte-specific markers was evaluated by quantitative real-time polymerase chain reaction. To examine the effect of Y27632 on Smad2/3 phosphorylation induced by TGF-β1, western blot analysis was also performed. The stimulation of TGF-β1 in SMSCs resulted in the activation of the RhoA/ROCK pathway and concomitantly induced cytoskeletal reorganization, which was specifically blocked by C3 transferase and Y27632. The TGF-β-induced gene expression of Sox9, type I collagen, type II collagen and aggrecan was also inhibited by both C3 transferase and Y27632, at different levels. Y27632 treatment reduced the phosphorylation of Smad2/3 in a concentration-dependent manner. These results demonstrate the RhoA/ROCK activation regulates chondrocyte-specific gene transcription and cytoskeletal organization induced by TGF-β1 by interacting with the Smad pathway. This may have significant implications for the successful utilization of SMSCs as a cell source for articular cartilage tissue engineering.

  7. Effects of Platelet-Rich Plasma & Platelet-Rich Fibrin with and without Stromal Cell-Derived Factor-1 on Repairing Full-Thickness Cartilage Defects in Knees of Rabbits

    Directory of Open Access Journals (Sweden)

    Soghra Bahmanpour

    2016-11-01

    Full Text Available Background: The purpose of this study was to create biomaterial scaffolds like platelet-rich plasma (PRP and platelet-rich fibrin (PRF containing stromal cell-derived factor-1 (SDF1 as a chemokine to induce hyaline cartilage regeneration of rabbit knee in a full thickness defect. Methods: We created a full thickness defect in the trochlear groove of thirty-six bilateral knees of eighteen mature male rabbits. The knees were randomly divided into six groups (group I: untreated control, group II: PRP, group III: PRF, group IV: Gelatin+SDF1, group V: PRP+SDF1, and group VI: PRF+SDF1. After four weeks, the tissue specimens were evaluated by macroscopic examination and histological grading, immunofluorescent staining for collagen type II, and analyzed for cartilage marker genes by real-time PCR. The data were compared using statistical methods (SPSS 20, Kruskal-Wallis test, Bonferroni post hoc test and P<0.05. Results: Macroscopic evaluations revealed that international cartilage repair society (ICRS scores of the PRF+SDF1 group were higher than other groups. Microscopic analysis showed that the ICRS score of the PRP group was significantly lower than other groups. Immunofluorescent staining for collagen II demonstrated a remarkable distribution of type II collagen in the Gel+SDF1, PRP+SDF1 and PRF+SDF1 groups compared with other groups. Real-time PCR analysis revealed that mRNA expression of SOX9 and aggrecan were significantly greater in the PRF+SDF1, PRP+SDF1, Gel+SDF1 and PRF groups than the control group (P<0.05. Conclusion: Our results indicate that implantation of PRF scaffold containing SDF1 led to the greatest evaluation scores of full-thickness lesions in rabbits.

  8. Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Amilton M Fernandes

    Full Text Available Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM derived mesenchymal stem cells (MSCs from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin, ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.

  9. Prior Inoculation with Type B Strains of Francisella tularensis Provides Partial Protection against Virulent Type A Strains in Cottontail Rabbits.

    Directory of Open Access Journals (Sweden)

    Vienna R Brown

    Full Text Available Francisella tularensis is a highly virulent bacterium that is capable of causing severe disease (tularemia in a wide range of species. This organism is characterized into two distinct subspecies: tularensis (type A and holarctica (type B which vary in several crucial ways, with some type A strains having been found to be considerably more virulent in humans and laboratory animals. Cottontail rabbits have been widely implicated as a reservoir species for this subspecies; however, experimental inoculation in our laboratory revealed type A organisms to be highly virulent, resulting in 100% mortality following challenge with 50-100 organisms. Inoculation of cottontail rabbits with the same number of organisms from type B strains of bacteria was found to be rarely lethal and to result in a robust humoral immune response. The objective of this study was to characterize the protection afforded by a prior challenge with type B strains against a later inoculation with a type A strain in North American cottontail rabbits (Sylvilagus spp. Previous infection with a type B strain of organism was found to lengthen survival time and in some cases prevent death following inoculation with a type A2 strain of F. tularensis. In contrast, inoculation of a type A1b strain was uniformly lethal in cottontail rabbits irrespective of a prior type B inoculation. These findings provide important insight about the role cottontail rabbits may play in environmental maintenance and transmission of this organism.

  10. Significance of soluble growth factors in the chondrogenic response of human umbilical cord matrix stem cells in a porous three dimensional scaffold

    Directory of Open Access Journals (Sweden)

    RS Nirmal

    2013-11-01

    Full Text Available Stem cell based tissue engineering has emerged as a promising strategy for articular cartilage regeneration. Foetal derived mesenchymal stem cells (MSCs with their ease of availability, pluripotency and high expansion potential have been demonstrated to be an attractive cell source over adult MSCs. However, there is a need for optimisation of chondrogenic signals to direct the differentiation of these multipotent MSCs to chondrogenic lineage. In this study we have demonstrated the in vitro chondrogenesis of human umbilical cord matrix MSCs in three dimensional PVA-PCL (polyvinyl alcohol-polycaprolactone scaffolds in the presence of the individual growth factors TGFβ1, TGFβ3, IGF, BMP2 and their combination with BMP2. Gene expression, histology and immunohistology were evaluated after 28 d culture. The induced cells showed the feature of chondrocytes in their morphology and expression of typical chondrogenic extracellular matrix molecules. Moreover, the real-time PCR assay has shown the expression of gene markers of chondrogenesis, SOX9, collagen type II and aggrecan. The expression of collagen type I and collagen type X was also evaluated. This study has demonstrated the successful chondrogenic induction of human umbilical cord MSCs in 3D scaffolds. Interestingly, the growth factor combination of TGF-β3 and BMP-2 was found to be more effective for chondrogenesis as shown by the real-time PCR studies. The findings of this study suggest the importance of using growth factor combinations for successful chondrogenic differentiation of umbilical cord MSCs.

  11. Sensitivity analysis of reflector types and impurities in a 10 MW MTR type nuclear research reactor

    International Nuclear Information System (INIS)

    Khattab, K.; Khamis, I.

    2008-01-01

    The 2-D and 3-D neutronics models for 10 MW nuclear research reactor of MTR type have been developed and presented in this paper. Our results agree very well with the results of seven countries mentioned in the IAEA-TECDOC-233. To study the effect of reflector types on the reactor effective multiplication factor, five types of reflectors such as pure beryllium, beryllium, heavy water, carbon and water are selected for this study. The pure beryllium is found to be the most efficient reflector in this group. The effect of the most important impurities, which exist on the beryllium reflector such as iron, silicon and aluminium on the reactor multiplication factor, have been analyzed as well. It is found that the iron impurity affects the reactor multiplication factor the most compared to silicon and aluminium impurities. (author)

  12. Age at menopause, reproductive life span, and type 2 diabetes risk results from the EPIC-interAct Study

    NARCIS (Netherlands)

    Brand, J.S.; Schouw, van der Y.T.; Onland-Moret, N.; Sharp, S.J.; Feskens, E.J.M.

    2013-01-01

    OBJECTIVEAge at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.RESEARCH DESIGN AND

  13. A rewriting view of simple typing

    NARCIS (Netherlands)

    Stump, A.; Zantema, H.; Kimmell, G.; El Haj Omar, R.

    2012-01-01

    This paper shows how a recently developed view of typing as small-step abstract reduction, due to Kuan, MacQueen, and Findler, can be used to recast the development of simple type theory from a rewriting perspective. We show how standard meta-theoretic results can be proved in a completely new way,

  14. A rewriting view of simple typing

    NARCIS (Netherlands)

    Stump, A.; Zantema, H.; Kimmell, G.; El Haj Omar, R.

    2013-01-01

    This paper shows how a recently developed view of typing as small-step abstract reduction, due to Kuan, MacQueen, and Findler, can be used to recast the development of simple type theory from a rewriting perspective. We show how standard meta-theoretic results can be proved in a completely new way,

  15. COMPARISON OF RESULTS OF THERMAL TESTS OF BALCONY DOORS

    Directory of Open Access Journals (Sweden)

    Golubev Stanislav Sergeevich

    2012-10-01

    Full Text Available Results of thermal tests of balcony doors are presented in the article. In the course of the research project, two types of doors were tested. The first type represents a PVC frame door (width 82 mm; it has a triple glazing (4K-16Ar-4-16Ar-K4; its blank part represents a polystyrene sandwich panel (width 40 mm. The second type represents a PVC frame door (width 82 mm, that has a triple glazing (4K-16Ar-4-16Ar-K4 and composite PVC panels. The testing procedure and processing results are described in the article. The test has demonstrated that the thermal resistance value of the balcony door of the first type exceeds the thermal resistance value of the balcony door of the second type.

  16. Fitting Formulae and Constraints for the Existence of S-type and P-type Habitable Zones in Binary Systems

    International Nuclear Information System (INIS)

    Wang Zhaopeng; Cuntz, Manfred

    2017-01-01

    We derive fitting formulae for the quick determination of the existence of S-type and P-type habitable zones (HZs) in binary systems. Based on previous work, we consider the limits of the climatological HZ in binary systems (which sensitively depend on the system parameters) based on a joint constraint encompassing planetary orbital stability and a habitable region for a possible system planet. Additionally, we employ updated results on planetary climate models obtained by Kopparapu and collaborators. Our results are applied to four P-type systems (Kepler-34, Kepler-35, Kepler-413, and Kepler-1647) and two S-type systems (TrES-2 and KOI-1257). Our method allows us to gauge the existence of climatological HZs for these systems in a straightforward manner with detailed consideration of the observational uncertainties. Further applications may include studies of other existing systems as well as systems to be identified through future observational campaigns.

  17. Fitting Formulae and Constraints for the Existence of S-type and P-type Habitable Zones in Binary Systems

    Energy Technology Data Exchange (ETDEWEB)

    Wang Zhaopeng; Cuntz, Manfred, E-mail: zhaopeng.wang@mavs.uta.edu, E-mail: cuntz@uta.edu [Department of Physics, University of Texas at Arlington, Arlington, TX 76019 (United States)

    2017-10-01

    We derive fitting formulae for the quick determination of the existence of S-type and P-type habitable zones (HZs) in binary systems. Based on previous work, we consider the limits of the climatological HZ in binary systems (which sensitively depend on the system parameters) based on a joint constraint encompassing planetary orbital stability and a habitable region for a possible system planet. Additionally, we employ updated results on planetary climate models obtained by Kopparapu and collaborators. Our results are applied to four P-type systems (Kepler-34, Kepler-35, Kepler-413, and Kepler-1647) and two S-type systems (TrES-2 and KOI-1257). Our method allows us to gauge the existence of climatological HZs for these systems in a straightforward manner with detailed consideration of the observational uncertainties. Further applications may include studies of other existing systems as well as systems to be identified through future observational campaigns.

  18. Different collagen types define two types of idiopathic epiretinal membranes

    OpenAIRE

    Kritzenberger , Michaela; Junglas , Benjamin; Framme , Carsten; Helbig , Horst; Gabel , Veit-Peter; Fuchshofer , Rudolf; Tamm , Ernst R; Hillenkamp , Jost

    2011-01-01

    Abstract Aims: To identify differences in extracellular matrix contents between idiopathic epiretinal membranes (IEM) of cellophane macular reflex (CMRM) or preretinal macular fibrosis (PMFM) type. Methods and results: IEM were analyzed by light and quantitative transmission electron microscopy, immunohistochemistry, and Western blotting. Substantial differences between CMRM and PMFM were observed regarding the nature of extracellular fibrils. In CMRM, the fibrils were thin with...

  19. Change in the electrical conductivity of SnO2 crystal from n-type to p-type conductivity

    International Nuclear Information System (INIS)

    Villamagua, Luis; Stashans, Arvids; Lee, Po-Ming; Liu, Yen-Shuo; Liu, Cheng-Yi; Carini, Manuela

    2015-01-01

    Highlights: • Switch from n-type to p-type conductivity in SnO 2 has been studied. • Computational DFT + U method where used. • X-ray diffraction and X-ray photoelectron spectroscopy where used. • Al- and N-codoped SnO 2 compound shows stable p-type conductivity. • Low resistivity (3.657 × 10 −1 Ω cm) has been obtained. • High carrier concentration (4.858 × 10 19 cm −3 ) has been obtained. - Abstract: The long-sought fully transparent technology will not come true if the n region of the p–n junction does not get as well developed as its p counterpart. Both experimental and theoretical efforts have to be used to study and discover phenomena occurring at the microscopic level in SnO 2 systems. In the present paper, using the DFT + U approach as a main tool and the Vienna ab initio Simulation Package (VASP) we reproduce both intrinsic n-type as well as p-type conductivity in concordance to results observed in real samples of SnO 2 material. Initially, an oxygen vacancy (1.56 mol% concentration) combined with a tin-interstitial (1.56 mol% concentration) scheme was used to achieve the n-type electrical conductivity. Later, to attain the p-type conductivity, crystal already possessing n-type conductivity, was codoped with nitrogen (1.56 mol% concentration) and aluminium (12.48 mol% concentration) impurities. Detailed explanation of structural changes endured by the geometry of the crystal as well as the changes in its electrical properties has been obtained. Our experimental data to a very good extent matches with the results found in the DFT + U modelling

  20. Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information.

    Science.gov (United States)

    Vogel, Ulrich; Szczepanowski, Rafael; Claus, Heike; Jünemann, Sebastian; Prior, Karola; Harmsen, Dag

    2012-06-01

    Neisseria meningitidis causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.