Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease

In an open label study 63 patients with idiopathic Parkinson's disease suffering from end-of-dose akinesia were switched from a treatment with a L-DOPA standard formulation to a combined therapy of L-DOPA standard in the morning and L-DOPA slow release (levodopa, benserazide, Madopar Depot) at the remaining single doses. Substitution of L-DOPA standard by L-DOPA slow release took on average 2-4 weeks. Patients were subsequently treated for 6 months. Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy. In 20 centers 37 men and 26 women were included into the study. 27 males and 20 females completed the 6 month treatment period. Before switching, the patients received 438 +/- 213 mg a day L-DOPA standard, after conversion, the average dose was 617 +/- 323 mg L-DOPA slow release and 107 +/- 95 mg L-DOPA standard a day. Fluctuations during the day and at night which were rated according to a newly developed clinical 5-point rating scale were significantly improved by the treatment regimen from 2.8 +/- 0.9 to 1.4 +/- 1.2. Additionally, parkinsonian symptoms were significantly reduced during the ON-phase as there was a significant decrease of the Webster rating score from 12.0 +/- 4.6 to 7.1 +/- 4.0. Quality of life as measured by subjective ratings of the patients improved. The tolerability of the new formulation of L-DOPA was rated to be good in 51.1% and very good in 48.9%. The results of this open label study suggest that the combination of L-DOPA standard in the morning and L-DOPA slow release formulation at the following time points can be an efficient therapy in parkinsonian patients who suffer form L-DOPA related end-of-dose motor akinesia.     

New strategies for intraoperative myocardial protection

In the past, most strategies for intraoperative myocardial protection were developed in models using nondiseased adult hearts from various animal species. In the clinical setting, however, myocardial status in cardiac patients may be quite different and there is a need to adapt our current protective strategies to the actual pathophysiological status of the heart. In the immature heart as well as in the senescent heart, current protective techniques have been shown to be deficient and further research is required. New insights have been gained into the pathophysiological processes underlying chronic ischemic left ventricular dysfunction in the "hibernating" myocardium. It has been shown that viability in these hearts is associated with subcellular alterations related to dedifferentiation of the myocytes. This finding explains the delayed recovery in function of these hearts after revascularization and the need for intraoperative protective strategies focusing on the prevention of stunning in the nonhibernating segments. Tepid continuous retrograde blood cardioplegia is suggested as the optimal technique. Unraveling the mechanisms of preconditioning in the heart and understanding endogenous myocardial protection may provide clues for novel cardioprotective techniques. Adenosine itself may be used as an adjunct to cardioplegia, and treatment with adenosine regulating agents or nucleoside transport inhibitors shows promising results. Like adenosine, other hyperpolarizing agents (potassium-channel openers) are suggested for arrest of the heart instead of the depolarizing agents commonly used in cardioplegia. Finally, the role of Na(+)-H+ exchange in the development of ischemic and postischemic injury has become more clear. By the use of a new selective Na(+)-H+ exchange inhibitor, postischemic contracture can be dramatically reduced and contractility improved. This opens prospective approaches in emergency coronary bypass surgery for evolving myocardial infarction.     

Composites of hydroxyapatite and bisphosphonate: properties and alveolar bone response

A composite was made by adsorption of the bisphosphonate [(3-dimethylamino-1-hydroxypropylidene)-1,1-bisphosphonate; dimethyl-APD] into an hydroxyapatite (HA) tube. Adsorbed dimethyl-APD did not change the bulk properties of the HA tube but the surface properties were altered. The amount of 0.1 mmol/L dimethyl-APD adsorbed into the HA tube was 0.78 ( ± 0.20) g after 4 weeks. The composite tube of HA and dimethyl-APD placed after extraction of teeth in the premolar regions of dogs were biocompatible, stable and bonded strongly and intimately to the alveolar bone. Although there was no bone resorption around the composite tubes, no conclusion can be drawn yet from this study as far as local inhibition of alveolar bone resorption is concerned.     

Simulation analysis and experimental verification of coal suction characteristics of the new railway tunnel fallen coal dust collection device北大核心CSCD

Due to air turbulence, large areas of coal will fall when the special coal-transportation trains pass the tunnel exits and entrances. Aiming at the problems of low efficiency and high cost of manual cleaning for long distance coal cleaning in the tunnel, a new railway tunnel fallen coal dust collection device which was composed of a main conveying coal feeding pipe and multiple branch pipes of coal suction was designed. It was used to clean the small particles and lightweight railway tunnel fallen coal. Firstly, the gas-solid two-phase flow model based on the Euler-Lagrange approach for the design of the main conveying coal feeding pipe was established in the coal conveying pipelines. Secondly, the effect of the coal particles' incident angle and multiple branch pipe spacing on the main coal conveying pipe flow field, which was based on Fluent finite element simulation software, was studied. What was more, the optimal angle of incidence and the optimal value of the number of branch coal suction pipe, which was installed on the main conveying pipe, were analyzed. Finally, the finite element simulation was verified by field test. Simulation and experimental results showed that it was more conducive to the railway tunnel fallen coal transportation when coal particles' incident angle was less than 45° and the branch pipe spacing was in the vicinity of 750 mm. For that when incident angle was less than 45°, the main conveying coal pipe pressure-drop became weaker and particle flow could obtain large horizontal transport velocity. And when the branch pipe spacing was in the vicinity of 750 mm, the horizontal transport velocity had a smaller fluctuation range and the transportation of coal was larger than that of the other groups. The research results are of great significance to improve the structure of the main conveying coal pipe, increase the efficiency of tunnel coal conveying and optimize the railway tunnel coal dust collection device.     

Wire + Arc Additive Manufacturing

Depositing large components (>10?kg) in titanium, aluminium, steel and other metals is possible using Wire + Arc Additive Manufacturing. This technology adopts arc welding tools and wire as feedstock for additive manufacturing purposes. High deposition rates, low material and equipment costs, and good structural integrity make Wire+Arc Additive Manufacturing a suitable candidate for replacing the current method of manufacturing from solid billets or large forgings, especially with regards to low and medium complexity parts. A variety of components have been successfully manufactured with this process, including Ti–6Al–4V spars and landing gear assemblies, aluminium wing ribs, steel wind tunnel models and cones. Strategies on how to manage residual stress, improve mechanical properties and eliminate defects such as porosity are suggested. Finally, the benefits of non-destructive testing, online monitoring and in situ machining are discussed.     

Enhanced mortar approach to characterize the effect of reclaimed asphalt pavement on virgin binder true grade

The asphalt community seeks a solvent-free method to determine the properties of RAP binder and those of its blends with virgin binders. A promising approach is to test mortars composed of fine fractions of RAP and a virgin binder, and to calculate grade change rate (GCR) to predict blended binder true grade at any binder replacement rate (BRR). However, the existing mortar approach underestimates the effect of RAP on binder grade, particularly at high temperatures. This study identified the use of a shift factor in the existing method as the source of underestimations. An alternative data analysis method was developed, which eliminates the shift factor by using the relationship between binder and mortar properties. Dynamic shear rheometer tests were conducted on a total of 12 mortar combinations, including 4 virgin binders and 3 RAP sources at a BRR of 15%, and then, RAP GCR values were determined by following both the existing and the alternative methods. Satisfactory comparisons were only observed between grades predicted with the alternative method and measured values of manual RAP binder blends: the average difference was lower than 1 °C for BRR of 15 and 30%, and < 4 °C for BRR of 100%. This not only validated the alternative method but also substantiated that RAP GCR is constant, i.e., the grade of RAP blends linearly increased with BRR. Further evaluation of the enhanced mortar approach is recommended at intermediate and low temperatures as well as with blends including recycled asphalt shingles.     

Surface energy-mediated fibronectin adsorption and osteoblast responses on nanostructured diamond

Nanostructured diamond have potential applications in many biomedical related fields and demonstrated extraordinary capacity to influence cellular responses. Studying the surface property of nanodiamond and its influence to protein adsorption and subsequent cellular responses along with the mechanism behind such capacity becomes more important. Here the role of surface energy associated with nanostructured diamond in modulating fibronectin and osteoblast(OB, bone forming cells) responses was investigated. Nanocrystalline diamond(NCD) and submicron crystalline diamond(SMCD) films with controllable surface energy were prepared by microwave-enhanced plasma chemical vapor deposition(MPCVD) techniques. Fibronectin adsorption on the diamond films with varied surface energy values was measured via the enzyme-linked immunosorbent assay(ELISA) and the relationship between the surface energy and fibronectin adsorption was studied. The result indicated that fibronectin adsorption on nanostructured surfaces was closely related to both surface energy and material microstructures. The spreading and migration of OB aggregates(each containing 30–50 cells) on the NCD with varied surface energy values were also studied. The result indicates a correlation between the cell spreading and migration on nanodiamond and the surface energy of nanostructured surface.