Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response

Engineering of N. benthamiana L. plants for production of N-acetylgalactosamine-glycosylated proteins - towards development of a plant-based platform for production of protein therapeutics with mucin type O-glycosylation

<p>Abstract</p> <p>Background</p> <p>Mucin type O-glycosylation is one of the most common types of post-translational modifications that impacts stability and biological functions of many mammalian proteins. A large family of UDP-GalNAc polypeptide:N-acetyl-α-galactosaminyltransferases (GalNAc-Ts) catalyzes the first step of mucin type O-glycosylation by transferring GalNAc to serine and/or threonine residues of acceptor polypeptides. Plants do not have the enzyme machinery to perform this process, thus restricting their use as bioreactors for production of recombinant therapeutic proteins.</p> <p>Results</p> <p>The present study demonstrates that an isoform of the human GalNAc-Ts family, GalNAc-T2, retains its localization and functionality upon expression in <it>N. benthamiana </it>L. plants. The recombinant enzyme resides in the Golgi as evidenced by the fluorescence distribution pattern of the GalNAc-T2:GFP fusion and alteration of the fluorescence signature upon treatment with Brefeldin A. A GalNAc-T2-specific acceptor peptide, the 113-136 aa fragment of chorionic gonadotropin β-subunit, is glycosylated <it>in vitro </it>by the plant-produced enzyme at the "native" GalNAc attachment sites, Ser-121 and Ser-127. Ectopic expression of GalNAc-T2 is sufficient to "arm" tobacco cells with the ability to perform GalNAc-glycosylation, as evidenced by the attachment of GalNAc to Thr-119 of the endogenous enzyme endochitinase. However, glycosylation of highly expressed recombinant glycoproteins, like magnICON-expressed <it>E. coli </it>enterotoxin B subunit:<it>H. sapiens </it>mucin 1 tandem repeat-derived peptide fusion protein (LTBMUC1), is limited by the low endogenous UDP-GalNAc substrate pool and the insufficient translocation of UDP-GalNAc to the Golgi lumen. Further genetic engineering of the GalNAc-T2 plants by co-expressing <it>Y. enterocolitica </it>UDP-GlcNAc 4-epimerase gene and <it>C. elegans </it>UDP-GlcNAc/UDP-GalNAc transporter gene overcomes these limitations as indicated by the expression of the model LTBMUC1 protein exclusively as a glycoform.</p> <p>Conclusion</p> <p>Plant bioreactors can be engineered that are capable of producing Tn antigen-containing recombinant therapeutics.</p

Post-Operative Carbonate-Apatite Formation in PEO/PBT Copolymers (Polyactive®)

Previous studies have stressed the importance of calcification of the polyethylene oxide (PEO) I polybutylene terephthalate (PBT) copolymer surface by establishing a direct relation with the occurrence of bone-bonding. Here, we characterized the morphology as well as the composition of this post-operative reaction product in PEOIPBT copolymers. X-ray · photoelectron spectroscopical results demonstrated the ability of PEOIPBT copolymers to rapidly adsorb calcium ions from fluids. After subcutaneous implantation in rats, it was shown that polymer calcification comprised plate-shaped crystals, whereas an electron-dense layer was frequently encountered at the interface. Cells with a characteristic morphology were directly apposed to abundantly calcified surfaces, indicating the biocompatible nature of the material. Subcutaneous calcification was composed of a carbonate-apatite structure with a crystallinity comparable to bone mineral as demonstrated by Fourier transformed infrared spectroscopy and X-ray diffraction. It was concluded that the post-operative reaction product in PEOIPBT copolymers is, in morphology and composition, highly comparable to the carbonate-containing apatitic surface layer generated on acknowledged bioactive substrates and similar to the inorganic phase of bone apatite. This may, partially, explain the bone-bonding behaviour of PEOIPBT copolymers

Proceedings, International Taxus Symposium, October 1, 1975

History and development of Taxus in the U.S. / Ray A. Keen -- The best of the Taxus cultivars / L. C. Chadwick -- Poisonous properties of Taxus / Jack L. Beal -- Production of Taxus / Arie J. Radder -- Effective use of Taxus in the landscape / Clarence E. Lewis -- Taxus species and hybrids / Harold G. Hillier -- Japanese yew (Taxus cuspidata) / Makoto Kawase -- Fertilizing Taxus for optimum growth / Elton M. Smith -- Taxus insects: problems and research in Ohio / David G. Nielsen -- Taxus locations in the Secrest Arboretu

Ectopic bone formation in cell-seeded poly(ethylene oxide)/poly(butylene terephthalate) copolymer scaffolds of varying porosity

Scaffolds from poly(ethylene oxide) and poly(butylene terephthalate), PEOT/PBT, with a PEO molecular weight of 1,000 and a PEOT content of 70 weight% (1000PEOT70PBT30) were prepared by leaching salt particles (425–500 μm). Scaffolds of 73.5, 80.6 and 85.0% porosity were treated with a CO2 gas plasma and seeded with rat bone marrow stromal cells (BMSCs). After in vitro culture for 7 days (d) in an osteogenic medium the scaffolds were subcutaneously implanted for 4 weeks in nude mice. Poly(d, l-lactide) (PDLLA) and biphasic calcium phosphate (BCP) scaffolds were included as references. After 4 weeks (wks) all scaffolds showed ectopic formation of bone and bone marrow. For the scaffolds of different porosities, no significant differences were observed in the relative amounts of bone (7–9%) and bone marrow (6–11%) formed, even though micro computed tomography (μ-CT) data showed considerable differences in accessible pore volume and surface area. 1000PEOT70PBT30 scaffolds with a porosity of 85% could not maintain their original shape in vivo. Surprisingly, 1000PEOT70PBT30 scaffolds with a porosity of 73.5% showed cartilage formation. This cartilage formation is most likely due to poorly accessible pores in the scaffolds, as was observed in histological sections. μ-CT data showed a considerably smaller accessible pore volume (as a fraction of the total volume) than in 1000PEOT70PBT30 scaffolds of 80.6 and 85.0% porosity. BMSC seeded PDLLA (83.5% porosity) and BCP scaffolds (29% porosity) always showed considerably more bone and bone marrow formation (bone marrow formation is approximately 40%) and less fibrous tissue ingrowth than the 1000PEOT70PBT30 scaffolds. The scaffold material itself can be of great influence. In more hydrophobic and rigid scaffolds like the PDLLA or BCP scaffolds, the accessibility of the pore structure is more likely to be preserved under the prevailing physiological conditions than in the case of hydrophilic 1000PEOT70PBT30 scaffolds. Scaffolds prepared from other PEOT/PBT polymer compositions, might prove to be more suited

The Influence of Lighting Settings on Museum’s Brand Image and Human Satisfaction in Exhibition Halls Using Virtual Reality

This paper analyses the influence of museum lighting design on the brand image and human satisfaction inside exhibition halls, taking Birmingham museum and art gallery as the case study of this research focusing on the exhibition that included the ancient Egyptian displays. Four different generated lighting scenes using virtual reality were generated. The results showed that the lighting had an impact on the brand image and affect the willingness of people to revisit the museum and recommend it to family and friends. This research considers the museum’s visitors as active participants not just passive recipients of environmental stimuli. The research tried to provide a better understanding of how the exhibition environment in terms of lighting is perceived and provide further insight into how exhibition lighting design can enhance the visitor’s experience and create a brand image. According to the research results, visitors tend to be willing to return and stay longer in the presence of diverse and exciting lighting settings

Prognostic value of myocardial perfusion scintigraphy in type 2 diabetic patients with mild, stable angina pectoris

Aim: To determine the prognostic value of reversible myocardial perfusion defects on myocardial perfusion scintigraphy (MPS) in patients with type 2 diabetes mellitus and mild anginal complaints. Methods and results: In the MERIDIAN trial, patients with diabetes mellitus type 2, stable, mild anginal symptoms (Canadian Cardiovascular Society classification (CCS) I-II/IV) and reversible perfusion defects were randomized to either continued pharmacological treatment or early invasive treatment. In this sub analysis, the severity of the myocardial perfusion defect was related to the occurrence of cardiac death and non-fatal myocardial infarction, in 319 patients (63% male, 65 ± 9 years). During follow-up (2.2 ± 0.6 years), 14 patients had a cardiac event: 3 in 171 patients without myocardial ischemia and 11 in 148 patients with myocardial ischemia. Annual event rates rose from 0.8% to 5.8% with increasing severity of myocardial ischemia. Multivariable analysis identified the presence of severe myocardial ischemia (hazard ratio (HR) 5.45, 95%CI 1.89-15.71) and insulin use (HR 4.00, 95%CI 1.25-12.75) as independent predictors of cardiac events. Conclusions: Type 2 diabetics with mild anginal symptoms with no or moderate myocardial ischemia have a low annual cardiac event rate. In patients with severe myocardial ischemia event rate increased 3-6 fold

Emerging technologies for the management of Type 1 diabetes in pregnancy

Purpose of Review: The purpose of the study is to discuss emerging technologies available in the management of type 1 diabetes in pregnancy. Recent Findings: The latest evidence suggests that continuous glucose monitoring (CGM) should be offered to all women on intensive insulin therapy in early pregnancy. Studies have additionally demonstrated the ability of CGM to help gain insight into specific glucose profiles as they relate to glycaemic targets and pregnancy outcomes. Despite new studies comparing insulin pump therapy to multiple daily injections, its effectiveness in improving glucose and pregnancy outcomes remains unclear. Sensor-integrated insulin delivery (also called artificial pancreas or closed-loop insulin delivery) in pregnancy has been demonstrated to improve time in target and performs well despite the changing insulin demands of pregnancy. Summary: Emerging technologies show promise in the management of type 1 diabetes in pregnancy; however, research must continue to keep up as technology advances. Further research is needed to clarify the role technology can play in optimising glucose control before and during pregnancy as well as to understand which women are candidates for sensor-integrated insulin delivery

Nonlinear wave interaction in coastal and open seas -- deterministic and stochastic theory

We review the theory of wave interaction in finite and infinite depth. Both of these strands of water-wave research begin with the deterministic governing equations for water waves, from which simplified equations can be derived to model situations of interest, such as the mild slope and modified mild slope equations, the Zakharov equation, or the nonlinear Schr\"odinger equation. These deterministic equations yield accompanying stochastic equations for averaged quantities of the sea-state, like the spectrum or bispectrum. We discuss several of these in depth, touching on recent results about the stability of open ocean spectra to inhomogeneous disturbances, as well as new stochastic equations for the nearshore

Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial

Contains fulltext : 109349.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. METHODS/DESIGN: The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. DISCUSSION: This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR2551, http://www.trialregister.nl