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• New volunteer program to support older patients in the emergency department (ED). • Training of volunteers was successful in increasing expertise and knowledge. • Volunteers' most frequent strategies applied were conversations. • Some difficulties occurred (e.g., coordination with staff, challenging patients). • Overall, the program is beneficial for patients, volunteers, and ED nurses. Admission to an emergency department (ED) is challenging for older patients with cognitive dysfunction (PWCD). Targeted patient-oriented approaches to improve the care for PWCD are needed. The aim of this pilot study was to design and evaluate a program for volunteers to support PWCD in the ED. Volunteers (N = 9) first received a training and during the following six months (N = 90 shifts), they accompanied PWCD (N = 112) during their stay. Results showed that the training increased volunteers' knowledge and expertise, but not shift-related self-efficacy. The most frequent strategies applied were conversations, holding hands and touching, and providing food and drinks. After six months, volunteers reported a great sense of meaningfulness and felt that they were highly appreciated by the patients. ED nurses' sceptical attitudes towards the program decreased. The program is beneficial for PWCD, appears to be meaningful for volunteers and is appreciated by ED nurses. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend troponin as the preferred biomarker to diagnose acute myocardial infarction (AMI) irrespective of the patient's sex. Recent reports have shown that sex-specific cut-offs should be considered but studies investigating sex-differences in the diagnostic accuracy of cardiac troponins are sparse. Objective To evaluate whether the diagnostic performance of cardiac troponin at admission (cTn) under routine conditions is influenced by patient's sex. Methods Between 15th of February 2009 and 15th of February 2010, women (n = 1648) and men (n = 2305) who presented to the emergency department with chest pain (n = 3954) were enrolled. The diagnostic performance of the routine, contemporary sensitive cTn assays (TnI; Stratus® CS, Siemens and TnT; Roche Diagnostics) at baseline for the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) was analyzed. Results NSTEMI was diagnosed in 7.3% (n = 287) of all patients. Men were more likely to be diagnosed with NSTEMI (8.8%; n = 202) as compared to women (5.2%; n = 85; p < 0.001). Sensitivity was 56.1% (95% CI: 44.7-67.0%) in women and 70.1% (95% CI: 63.1-76.4%) in men. Specificity was 96.8% (95% CI: 95.6-97.7%) in women and 94.5% (95% CI: 93.3-95.6%) in men. This resulted in a lower positive predictive value (PPV) for women (53.5%; 95% CI: 42.4-64.3) as compared to men (60.8%; 95% CI: 54.1-67.2) and a slightly higher negative predictive value (NPV) for women: 97.1% (95% CI: 96.0-97.9) vs. 96.3% (95% CI: 95.2-97.2) in men. Conclusions The findings of this study underline that the performance of cTn for the diagnosis of NSTEMI depends on a patient's sex, with a lower sensitivity and NPV in women. The definition and implementation of sex-specific cut-off values for cTn into clinical routine seems to be highly recommendable. [ABSTRACT FROM AUTHOR]

Despite the success of elastography in grading hepatic fibrosis by stiffness related noninvasive markers the relationship between viscoelastic constants in the liver and tissue structure remains unclear. We therefore studied the mechanical properties of 16 human liver specimens with different degrees of fibrosis, inflammation and steatosis by wideband magnetic resonance elastography (MRE) and static indentation experiments providing the specimens' static Young's modulus (E), dynamic storage modulus (G0) and dynamic loss modulus (G"). A frequency-independent shear modulus μ and a powerlaw exponent a were obtained by fitting G and G" using the two-parameter sprinpot model. The mechanical parameters were compared to the specimens' histology derived parameters such as degree of Fibrosis (F), inflammation score and fat score, amount of hydroxyproline (HYP) used for quantification of collagen, blood markers and presurgery in vivo function tests. The frequency averaged parameters G', G" and μ were significantly correlated with F (G': R=0.762, G": R=0.830; μ: R=0.744; all P < 0.01) and HYP (G': R=0.712; G": R=0.720; μ: R=0.731 ; all P < 0.01). The powerlaw exponent a displayed an inverse correlation with F (R = -0.590, P= 0.034) and a trend of inverse correlation with HYP (R = -0.470, P=0.089). The static Young's modulus E was less correlated with F (R=0.587, P=0.022) and not sensitive to HYP. Although inflammation was highly correlated with F (R = 0.773, P < 0.001), no interaction was discernable between inflammation and mechanical para-meters measured in this study. Other histological and blood markers as well as liver function test were correlated with neither F nor the measured mechanical parameters. In conclusion, viscoelastic constants measured by wideband MRE are highly sensitive to histologically proven fibrosis. Our results suggest that, in addition to the amount of connective tissue, subtle structural changes of the viscoelastic matrix determine the sensitivity of mechanical tissue properties to hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Abstract: Obesity and its associated health risks still demand for effective therapeutic strategies. Drugs and compositions derived from Oriental medicine such as green tea polyphenols attract growing attention. Previously, an extract from the Japanese spice bush Lindera obtusiloba (L. obtusiloba) traditionally used for treatment of inflammation and prevention of liver damage was shown to inhibit adipogenesis. Aiming for the active principle of this extract (+)-episesamin was identified, isolated and applied in adipogenic research using 3T3-L1 (pre)adipocytes, an established cell line for studying adipogenesis. With an IC50 of 10μM (+)-episesamin effectively reduced the growth of 3T3-L1 preadipocytes and decreased hormone-induced 3T3-L1 differentiation as shown by reduced accumulation of intracellular lipid droplets and diminished protein expression of GLUT-4 and vascular endothelial growth factor. Mechanistically, the presence of (+)-episesamin during hormone-induced differentiation provoked a reduced phosphorylation of ERK1/2 and β-catenin along with a reduced protein expression of peroxisome proliferator-activated receptor γ and a strongly increased protein expression of iNOS. Treatment of mature adipocytes with (+)-episesamin resulted in a reduction of intracellular stored lipid droplets and induced the proapoptotic enzymes caspases-3/-7. Besides interfering with adipogenesis, (+)-episesamin showed anti-inflammatory activity by counteracting the lipopolysaccharide- and tumor necrosis factor α-induced secretion of interleukin 6 by 3T3-L1 preadipocytes. In conclusion, (+)-episesamin seems to be the active drug in the L. obtusiloba extract being responsible for the inhibition of adipogenesis and, thus, should be evaluated as a novel potential complementary treatment for obesity. [Copyright &y& Elsevier]

Abstract: Obesity, the related metabolic syndrome and associated liver diseases represent an epidemic problem and demand for effective therapeutic strategies. In this regard, natural compounds derived from Oriental medicine such as green tea polyphenols influencing adipogenesis attract growing attention. In Korea, an aqueous extract from the Japanese spice bush Lindera obtusiloba is traditionally used for treatment of inflammation and prevention of liver damage. We here investigated effects of the L. obtusiloba extract on cell growth, apoptosis, Wnt signaling and differentiation of (im)mature adipocytes using 3T3-L1, an established cell line for studying adipogenesis. L. obtusiloba extract reduced the de‑novo DNA synthesis of 3T3-L1 preadipocytes in a concentration dependent manner with an IC50 of ∼135 μg/ml paralleled by induction of caspase‑3/7 mediated apoptosis. Hormone-induced 3T3‑L1 differentiation in the presence of L. obtusiloba extract resulted in a reduced accumulation of intracellular lipid droplets by 70%, in down-regulated expression of the adipogenesis-associated proteins glucose transporter-4 and vascular endothelial growth factor, in reduced secretion of the proadipogenic matrix metalloproteinase-2, and in dampened phosphorylation of the Wnt pathway effector protein β-catenin with subsequent diminished expression of the peroxisome proliferator-activated receptor-γ. Treatment of mature adipocytes with L. obtusiloba extract also significantly reduced intracellular lipid droplets. In addition to this strong interference of L. obtusiloba extract with adipogenesis, L. obtusiloba extract exerted anti-inflammatory effects. L. obtusiloba extract significantly attenuated lipopolysaccharide- and tumor necrosis factor α-induced secretion of IL-6 by preadipocytes, thus influencing insulin resistance and inflammatory state characterizing obesity. In conclusion, extracts of L. obtusiloba should be evaluated as a potential complementary treatment option for obesity associated with the metabolic syndrome. [Copyright &y& Elsevier]

Abstract: The extracellular matrix (ECM) attracts increasing attention as a store of biologically active molecules and as a reservoir of potent cell signalling molecules released by proteolytic action. Both, cytokines and proteases mediating such release are sequestered in the ECM. Here, we found matrix metalloproteinase (MMP) proforms closely associated with collagenous septae in fibrotic liver tissue, and we screened immobilized human placenta-derived collagen chains and other ECM proteins for MMP-binding activity. Following the establishment of a novel highly-efficient two-step chromatography procedure for the isolation of the purified α-chains of the pepsin-resistant triple-helical CVI fragment (CVI/PR) solid phase and surface plasmon resonance binding studies were performed. We identified the triple-helical domain of the α2 chain of microfilamentous CVI α2(VI) as having nanomolar affinity for the collagenases proMMP-1, -8 , -13 and stromelysin-1 (MMP-3), thus extending the repertoire of pericellular and substrate-based interactions of MMPs. Enzymatic activity assays enabled the correlation of MMP activity with CVI binding, in that α2(VI) chain-mediated inhibition of enzymatic activity is accompanied by increased binding. Similar results were shown for the gelatinase proMMP-9, whereas for proMMP-2, the α2(VI) chain at low concentrations seems to interfere with prodomain binding resulting in enhanced activity without scission of the prodomain. Stable complexes of proMMP-2 and α2(VI) chain competed with gelatinase binding to the preferred ligand, collagen type I. In conclusion, the α2(VI) chain modulates MMP availability by sequestering proMMPs in the ECM, blocking proteolytic activity. Therefore, CVI and especially its α2(VI) chain might serve as a lead structure for MMP-based therapeutics which modulates the action of these matrix components, e.g. in fibrosis and cancer. [Copyright &y& Elsevier]

Abstract: Liver fibrosis is characterized by high expression of the key profibrogenic cytokine transforming growth factor (TGF)-β and the natural tissue inhibitor of metalloproteinases (TIMP)-1, leading to substantial accumulation of extracellular matrix. Liver fibrosis originates from various chronic liver diseases, such as chronic viral hepatitis that, to date, cannot be treated sufficiently. Thus, novel therapeutics, for example, those derived from Oriental medicine, have gained growing attention. In Korea, extracts prepared from Lindera obtusiloba are used for centuries for treatment of inflammation, improvement of blood circulation and prevention of liver damage, but experimental evidence of their efficacy is lacking. We studied direct antifibrotic effects in activated hepatic stellate cells (HSCs), the main target cell in the fibrotic liver. L. obtusiloba extract (135 μg/ml) reduced the de novo DNA synthesis of activated rat and human HSCs by about 90%, which was not accompanied by cytotoxicity of HSC, primary hepatocytes and HepG2 cells, pointing to induction of cellular quiescence. As determined by quantitative polymerase chain reaction, simultaneous treatment of HSCs with TGF-β and L. obtusiloba extract resulted in reduction of TIMP-1 expression to baseline level, disruption of the autocrine loop of TGF-β autoinduction and increased expression of fibrolytic matrix metalloproteinase (MMP)-3. In addition, L. obtusiloba reduced gelatinolytic activity of HSC by interfering with profibrogenic MMP-2 activity. Since L. obtusiloba extract prevented intracellular oxidative stress experimentally induced by tert-butylhydroperoxide, we concluded that the direct antifibrotic effect of L. obtusiloba extract might be mediated by antioxidant activity. Thus, L. obtusiloba, traditionally used in Oriental medicine, may complement treatment of chronic liver disease. [Copyright &y& Elsevier]

Collagen XIV (CXIV) is a fibril-associated collagen that is mainly expressed in well differentiated tissues and in late embryonic development. Because CXIV is almost absent in proliferating and/or dedifferentiated tissues, a functional role in maintaining cell differentiation is suspected. We demonstrate antiproliferative, quiescence- and differentiation-inducing effects of human CXIV and its recombinant fragments on mesenchymal cells. In primary human fibroblasts, in mouse 3T3 fibroblasts and in 3T3-L1 preadipocytes, CXIV reduced de novo DNA synthesis by 75%, whereas cell numbers and viability remained unaltered. Cells showed no signs of apoptosis, and maximal proliferation was restored when serum was supplemented, thus indicating that CXIV induced reversible cellular quiescence. Exposure of fibroblasts to CXIV in vitro led to cellular bundles and clusters. CXIV also triggered tram-differentiation of 3T3-L1 preadipocytes into adipocytes, as could be shown by lipid accumulation and by expression of the glucose transporter Glut4. These effects were also observed with the amino-terminal recombinant fragment Gln29-Pro154 that harbors the first fibronectin type III domain and a 39-amino-acid extension, whereas no activity was found for all other recombinant CXIV fragments. Based on these finding the development of small molecular analogs that modulate fibroblast cell growth and differentiation, e.g. in wound healing and fibrosis, seems feasible. [ABSTRACT FROM AUTHOR]