Nuclear magnetic resonance-based metabolomics in respiratory medicine

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A simple trapped-ion architecture for high-fidelity Toffoli gates

We discuss a simple architecture for a quantum Toffoli gate implemented using three trapped ions. The gate, which in principle can be implemented with a single laser-induced operation, is effective under rather general conditions and is strikingly robust (within any experimentally realistic range of values) against dephasing, heating and random fluctuations of the Hamiltonian parameters. We provide a full characterization of the unitary and noise-affected gate using three-qubit quantum process tomography

Nuova luce sulla linea bastionata Cottonera. Malta crocevia nel Mediterraneo e fortezza

New Light on the Bastioned Line Cottonera. Malta as Fortress and Crossroads in the Mediterranean Sea In 1669 the Piedmontese engineer Antonio Maurizio Valperga was called to La Valletta by the Grand Master of the Order of Malta to attend to the modernisation of the coastal/island fortresses. His design was, however, considered unfeasibleand too extensive by contemporary military engineers. This short essay intends to clarify the presence of Valperga in Malta and shed light on his project through the criticisms of the famous engineer Gaspare Beretta, by means of unpublished papers conserved at the Biblioteca Trivulziana of Milan

NMR Profiling of Exhaled Breath Condensate Defines Different Metabolic Phenotypes of Non-Cystic Fibrosis Bronchiectasis

Nuclear-magnetic-resonance (NMR) profiling of exhaled breath condensate (EBC) provides insights into the pathophysiology of bronchiectasis by identifying specific biomarkers. We evaluated whether NMR-based metabolomics discriminates the EBC-derived metabolic phenotypes ("metabotypes") of 41 patients with non-cystic fibrosis (nCF) bronchiectasis of various etiology [24 subjects with Primary Ciliary Dyskinesia (PCD); 17 patients with bronchiectasis not associated with PCD (nCF/nPCD)], who were compared to 17 healthy subjects (HS). NMR was used for EBC profiling, and Orthogonal Projections to Latent Structures with partial least-squares discriminant analysis (OPLS-DA) was used as a classifier. The results were validated by using the EBC from 17 PCD patients not included in the primary analysis. Different statistical models were built, which compared nCF/nPCD and HS, PCD and HS, all classes (nCF/nPCD-PCD-HS), and, finally, PCD and nCF/nPCD. In the PCD-nCF/nPCD model, four statistically significant metabolites were able to discriminate between the two groups, with only a minor reduction of the quality parameters. In particular, for nCF/nPCD, acetone/acetoin and methanol increased by 21% and 18%, respectively. In PCD patients, ethanol and lactate increased by 25% and 28%, respectively. They are all related to lung inflammation as methanol is found in the exhaled breath of lung cancer patients, acetone/acetoin produce toxic ROS that damage lung tissue in CF, and lactate is observed in acute inflammation. Interestingly, a high concentration of ethanol hampers cilia beating and can be associated with the genetic defect of PCD. Model validation with 17 PCD samples not included in the primary analysis correctly predicted all samples. Our results indicate that NMR of EBC discriminates nCF/nPCD and PCD bronchiectasis patients from HS, and patients with nCF/nPCD from those with PCD. The metabolites responsible for between-group separation identified specific metabotypes, which characterize bronchiectasis of a different etiology

Metabolomics of COPD Pulmonary Rehabilitation Outcomes via Exhaled Breath Condensate

: Chronic obstructive pulmonary disease (COPD) is characterized by different phenotypes and clinical presentations. Therefore, a single strategy of pulmonary rehabilitation (PR) does not always yield the expected clinical outcomes as some individuals respond excellently, others discreetly, or do not respond at all. Fifty consecutive COPD patients were enrolled. Of them, 35 starting a 5-week PR program were sampled at admission (T0), after 2 (T2W) and 5 (T5W) weeks, while 15 controls not yet on PR were tested at T0 and T5W. Nuclear magnetic resonance (NMR) profiling of exhaled breath condensate (EBC) and multivariate statistical analysis were applied to investigate the relationship between biomarkers and clinical parameters. The model including the three classes correctly located T2W between T0 and T5W, but 38.71% of samples partially overlapped with T0 and 32.26% with T5W, suggesting that for some patients PR is already beneficial at T2W (32.26% overlapping with T5W), while for others (38.71% overlapping with T0) more time is required. Rehabilitated patients presented several altered biomarkers. In particular, methanol from T0 to T5W decreased in parallel with dyspnea and fatigue, while the walk distance increased. Methanol could be ascribed to lung inflammation. We demonstrated that the metabolic COPD phenotype clearly evolves during PR, with a strict relationship between clinical and molecular parameters. Methanol, correlating with clinical parameters, represents a useful biomarker for monitoring personalized outcomes and establishing more targeted protocols

Exploring Airway Diseases by NMR-Based Metabonomics: A Review of Application to Exhaled Breath Condensate

There is increasing evidence that biomarkers of exhaled gases or exhaled breath condensate (EBC) may help in detecting abnormalities in respiratory diseases mirroring increased, oxidative stress, airways inflammation and endothelial dysfunction. Beside the traditional techniques to investigate biomarker profiles, “omics” sciences have raised interest in the clinical field as potentially improving disease phenotyping. In particular, metabonomics appears to be an important tool to gain qualitative and quantitative information on low-molecular weight metabolites present in cells, tissues, and fluids. Here, we review the potential use of EBC as a suitable matrix for metabonomic studies using nuclear magnetic resonance (NMR) spectroscopy. By using this approach in airway diseases, it is now possible to separate specific EBC profiles, with implication in disease phenotyping and personalized therapy

Is Two Better Than One? The Impact of Doubling Training Volume in Severe COPD: A Randomized Controlled Study

Patients with severe chronic obstructive pulmonary disease (COPD) are unable to exercise at high intensities for sufficiently long periods of time to obtain true physiological training effects. It therefore appears sensible to increase training duration at sub-maximal exercise intensities to optimize the benefit of exercise training. We compared the effects on exercise tolerance of two endurance cycloergometer submaximal exercise protocols with different cumulative training loads (one (G1) versus two (G2) daily 40 min training sessions) both implemented over 20 consecutive days in 149 patients with COPD (forced expiratory volume at first second (FEV1): 39% predicted) admitted to an inpatient pulmonary rehabilitation program. Patients in G2 exhibited greater improvement (p = 0.011) in submaximal endurance time (from 258 (197) to 741 (662) sec) compared to G1 (from 303 (237) to 530 (555) sec). Clinically meaningful improvements in health-related quality of life, 6MWT, and chronic dyspnea were not different between groups. Doubling the volume of endurance training is feasible and can lead to an additional benefit on exercise tolerance. Future studies may investigate the applicability and benefits of this training strategy in the outpatient or community-based pulmonary rehabilitation settings to amplify the benefits of exercise interventions