Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: a pilot study.

BACKGROUND: The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES: We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS: We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS: Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS: Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patient

Regulation of fibroblast growth factor receptor signalling and trafficking by Src and Eps8

Fibroblast growth factor receptors (FGFRs) mediate a wide spectrum of cellular responses that are crucial for development and wound healing. However, aberrant FGFR activity leads to cancer. Activated growth factor receptors undergo stimulated endocytosis, but can continue to signal along the endocytic pathway. Endocytic trafficking controls the duration and intensity of signalling, and growth factor receptor signalling can lead to modifications of trafficking pathways. We have developed live-cell imaging methods for studying FGFR dynamics to investigate mechanisms that coordinate the interplay between receptor trafficking and signal transduction. Activated FGFR enters the cell following recruitment to pre-formed clathrin-coated pits (CCPs). However, FGFR activation stimulates clathrin-mediated endocytosis; FGF treatment increases the number of CCPs, including those undergoing endocytosis, and this effect is mediated by Src and its phosphorylation target Eps8. Eps8 interacts with the clathrin-mediated endocytosis machinery and depletion of Eps8 inhibits FGFR trafficking and immediate Erk signalling. Once internalized, FGFR passes through peripheral early endosomes en route to recycling and degredative compartments, through an Src- and Eps8-dependent mechanism. Thus Eps8 functions as a key coordinator in the interplay between FGFR signalling and trafficking. This work provides the first detailed mechanistic analysis of growth factor receptor clustering at the cell surface through signal transduction and endocytic trafficking. As we have characterised the Src target Eps8 as a key regulator of FGFR signalling and trafficking, and identified the early endocytic system as the site of Eps8-mediated effects, this work provides novel mechanistic insight into the reciprocal regulation of growth factor receptor signalling and trafficking

Pasta consumption and connected dietary habits: Associations with glucose control, adiposity measures, and cardiovascular risk factors in people with type 2 diabetes—TOSCA.IT study

Background: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. Methods: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. Results: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. Conclusions: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors

Diamond-Based Thin Film Bulk Acoustic Wave Resonator for Biomedical Applications

Nowadays it is in constant growing the development of thin film bulk acoustic resonators. If the piezoelectric material is going to be implanted in the human body, an important requirement is the biocompatibility of the implant. In this regard, Aluminum Nitride (AlN) has emerged as an attractive alternative for use in biomedical MicroElectroMechanical Systems. Ultrananocrystalline Diamond (UNCD) is a promising material to be used in biomedical applications, due to its extraordinary mulifunctionality; it is exceptional for implantable medical devices requiring stringent biological performance. Since both UNCD and AlN films can be processed via photolithography processes used in microfabrication, the integration of UNCD and AlN films provides the bases for developing a new generation of biocompatible Bio-MEMS/NEMS. Research and development was conducted to produce implantable MEMS devices: Pt/piezoelectric AlN/Pt layer heterostructure was grown and patterned on the UNCD membrane with a Ti adhesion layer. By applying voltages between the top and bottom Pt electrodes layers the piezoelectric AlN layer is energized. The feasibility of the fabrication of biocompatible AlN/diamond-based FBAR structure has been demonstrated.Fil: Zalazar, Martin. Universidad Nacional de Entre Rios. Facultad de Ingenieria. Departamento de Bioingenieria; ArgentinaFil: Guarnieri, Fabio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Centro de Investigación de Métodos Computacionales; Argentina. Universidad Nacional de Entre Rios. Facultad de Ingenieria. Departamento de Bioingenieria; Argentin

A first-principles study of oxygen vacancy pinning of domain walls in PbTiO3

We have investigated the interaction of oxygen vacancies and 180-degree domain walls in tetragonal PbTiO3 using density-functional theory. Our calculations indicate that the vacancies do have a lower formation energy in the domain wall than in the bulk, thereby confirming the tendency of these defects to migrate to, and pin, the domain walls. The pinning energies are reported for each of the three possible orientations of the original Ti-O-Ti bonds, and attempts to model the results with simple continuum models are discussed.Comment: 8 pages, with 3 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/lh_dw/index.htm

Giant Enhancement of Surface Second Harmonic Generation in BaTiO_3 due to Photorefractive Surface Wave Excitation

We report observation of strongly enhanced surface SHG in BaTiO_3 due to excitation of a photorefractive surface electromagnetic wave. Surface SH intensity may reach 10^{-2} of the incident fundamental light intensity. Angular, crystal orientation and polarization dependencies of this SHG are presented. Possible applications of this effect in nonlinear surface spectroscopy are discussed.Comment: 5 pages, 6 figures, submitted to Physical Review Letters on the 3/29/199

Electronic structure and ferroelectricity in SrBi2Ta2O9

The electronic structure of SrBi2Ta2O9 is investigated from first-principles, within the local density approximation, using the full-potential linearized augmented plane wave (LAPW) method. The results show that, besides the large Ta(5d)-O(2p) hybridization which is a common feature of the ferroelectric perovskites, there is an important hybridization between bismuth and oxygen states. The underlying static potential for the ferroelectric distortion and the primary source for ferroelectricity is investigated by a lattice-dynamics study using the Frozen Phonon approach.Comment: 17 pages, 7 figures. Phys. Rev. B, in pres

Polyphenol intake and cardiovascular risk factors in a population with\ua0type 2 diabetes: The TOSCA.IT study.

Summary Background The role of polyphenol intake on cardiovascular risk factors is little explored, particularly in people with diabetes. Aim: To evaluate the association between the intake of total polyphenols and polyphenol classes with the major cardiovascular risk factors in a population with type 2 diabetes. Methods Dietary habits were investigated in 2573 males and females participants of the TOSCA.IT study. The European Prospective Investigation on Cancer and Nutrition (EPIC) questionnaire was used to assess dietary habits. In all participants, among others, we assessed anthropometry, plasma lipids, blood pressure, C-reactive protein and HbA1c following a standard protocol. The USDA and Phenol-Explorer databases were used to estimate the polyphenol content of the habitual diet. Results Average intake of polyphenols was 683.3 \ub1 5.8 mg/day. Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%, respectively). After adjusting for potential confounders, people with the highest intake of energy-adjusted polyphenols (upper tertile) had a more favorable cardiovascular risk factors profile as compared to people with the lowest intake (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9 mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs 148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs 134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was 1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the analysis was conducted separately for flavonoids or phenolic acids, the two main classes of polyphenols consumed in this population. Conclusions Polyphenol intake is associated with a more favorable cardiovascular risk factors profile, independent of major confounders. These findings support the consumption of foods and beverages rich in different classes of polyphenols particularly in people with diabetes. Clinical trial http://www.clinicaltrials.gov; Study ID number: NCT00700856