Aerobic training and angiogenesis activation in patients with stable chronic heart failure: a preliminary report.

The pathophysiology of chronic heart failure (CHF) involves multiple hystologic and molecular alterations. To determine the effects of physical training on circulating endothelial progenitor cells (EPCs), angiogenesis (angiogenin, angiopoietin-1 and -2, VEGF, Tie-2, SDF-1α) and inflammation (IL-6, CRP), we compared data obtained from 11 CHF pts before and after 3 months aerobic exercise training, to those from 10 non trained CHF pts (CHF-C group, age 64 + 2 years, NYHA 2). At the end of the study, EPCs count and AP-2 serum levels significantly increased in the CHF-TR group. These preliminary data suggest a significant effect of even a short program of physical training on angiogenic activation and endothelial dysfunction

Effects of diffusion induced recrystallization on volume diffusion in the copper-nickel system

Abstract The effects of diffusion induced recrystallization (DIR) on volume diffusion in the Cu(Ni) system was investigated. Cu-Ni diffusion couples annealed at 500, 550, 600, and 650°C for 120 and 200 h were used to calculate the volume diffusion for the Cu(Ni) binary system. Using characterization techniques such as focused ion beam (FIB) and transmission electron microscopy (TEM), observation of the interdiffusion zone revealed areas containing DIR and non-DIR. The volume diffusion of Ni into Cu across the non-DIR regions were calculated using the Boltzmann-Matano (B/M) method at 1 wt% Ni to be 8.05E-21, 9.88E-20, 4.53E-19, 2.67E-18 m 2 /s for 500, 550, 600, and 650°C, respectively. Calculations of volume diffusion across the DIR zones were approximately three to four orders of magnitude higher than the volume diffusion based on the non-DIR information. Literature values for volume diffusion in the Cu(Ni) system are also higher than the non-DIR values by approximately one order of magnitude, implying that previous values may contain grain boundary contributions

Short and long term surface chemistry and wetting behaviour of stainless steel with 1D and 2D periodic structures induced by bursts of femtosecond laser pulses

We investigate the short and long term wettability of laser textured stainless steel samples in order to better understand the interplay between surface topography and chemistry. Very different 1D and 2D periodic as well as non-periodic surface patterns were produced by exploiting the extreme flexibility of a setup consisting of five rotating birefringent crystals, which allows generating bursts of up to 32 femtosecond laser pulses with fixed intra-burst delay of 1.5 ps. The change of the surface morphology as a function of the pulse splitting, the burst polarization state and the fluence was systematically studied. The surface topography was characterized by SEM and AFM microscopy. The laser textured samples exhibited, initially, superhydrophilic behaviour which, during exposure to ambient air, turned into superhydrophobic with an exponential growth of the static contact angle. The dynamic contact angle measurements revealed a water adhesive character which was explained by XPS analyses of the surfaces that showed an increase of hydrocarbons and more oxidized metal species with the aging. The characteristic water adhesiveness and superhydrophobicity of laser textured surfaces can be exploited for no loss droplet reversible transportation or harvesting

Successful private–public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines

The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMAPaediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. Conclusion: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private–public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of offpatent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes

Bicrystal growth and characterization of copper twist grain boundaries

Abstract Copper bicrystals with twist character were grown using the vertical Bridgman technique. Cu bicrystals were grown such that the grain boundary in each sample had a nominal twist misorientation consisting of either a low angle (108), a special angle (S5=36.878), or a high angle (458). The grain boundary plane in all cases was (1 0 0). The grain boundaries were grown using single-crystal seeds that were oriented to within AE 0.58 using the Laue back-reflection X-ray diffraction method. The misorientation of each twist boundary was characterized using electron backscattering diffraction patterns in a scanning electron microscope. All grain boundary misorientations were determined to be within the limits defined by the Brandon criterion. # 2001 Published by Elsevier Science B.V

Growth hormone secretagogues exert differential effects on skeletal muscle calcium homeostasis in male rats depending on the peptidyl/non-peptidyl structure

TheorexigenicandanaboliceffectsinducedbyghrelinandthesyntheticGHsecretagogues(GHSs) are thought to positively contribute to therapeutic approaches and the adjunct treatment of a number of diseases associated with muscle wasting such as cachexia and sarcopenia. However, manyquestionsaboutthepotentialutilityandsafetyofGHSsinboththerapyandskeletalmuscle functionremainunanswered.Byusingfura-2cytofluorimetrictechnique,wedeterminedtheacute effectsofghrelin,aswellasofpeptidylandnonpeptidylsyntheticGHSsoncalciumhomeostasis, a critical biomarker of muscle function, in isolated tendon-to-tendon male rat skeletal muscle fibers.ThesyntheticnonpeptidylGHSs,butnotpeptidylghrelinandhexarelin,wereabletosignificantlyincreaserestingcytosoliccalcium[Ca2]i.ThenonpeptidylGHS-induced[Ca2] iincrease was independent of GHS-receptor 1a but was antagonized by both thapsigargin/caffeine and cyclosporineA,indicatingtheinvolvementofthesarcoplasmicreticulumandmitochondria.EvaluationoftheeffectsofapseudopeptidylGHSandanonpeptidylantagonistoftheGHS-receptor 1a together with a drug-modeling study suggest the conclusion that the lipophilic nonpeptidyl structureofthetestedcompoundsisthekeychemicalfeaturecrucialfortheGHS-inducedcalcium alterationsintheskeletalmuscle.Thus,syntheticGHSscanhavedifferenteffectsonskeletalmuscle fibersdependingontheirmolecularstructures.Thecalciumhomeostasisdysregulationspecifically induced by the nonpeptidyl GHSs used in this study could potentially counteract the beneficial effects associated with these drugs in the treatment of muscle wasting of cachexia- or other age-related disorders

Secondary Prevention Through Cardiac Rehabilitation: Position Paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology

The purpose of this statement is to provide specific recommendations in regard to evaluation and intervention in each of the core components of cardiac rehabilitation (CR) to assist CR staff in the design and development of their programmes; the statement should also assist health care providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of such programmes. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, at national or at individual centre level, need to consider where and how structured programmes of CR can be delivered to the large constituency of patients now considered eligible for C

DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma

Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern. Functional analysis highlighted biological processes strongly related to embryonic development, tissue morphogenesis and cellular differentiation, including HOX, BMP and WNT. In addition, the analysis of epigenetic patterns and genome-wide methylation variability identified cDLBCL subgroups. Some of these epigenetic subtypes showed a concordance with the clinical outcome supporting the hypothesis that the accumulation of aberrant epigenetic changes results in a more aggressive behavior of the tumor. Collectively, our results suggest an important role of DNA methylation in DLBCL where aberrancies in transcription factors were frequently observed, suggesting an involvement during tumorigenesis. These findings warrant further investigation to improve cDLBCL prognostic classification and provide new insights on tumor aggressiveness