Airway microbiome and host inflammatory response in bronchiectasis

Non-cystic fibrosis bronchiectasis (hereby referred to as bronchiectasis) is a chronic respiratory disease characterized by irreversible dilation of bronchi in the context of chronic syndrome mainly represented by daily cough, sputum production and frequent pulmonary exacerbations. Bronchiectasis pathophysiology is recognised in the development of a vicious circle of infection, inflammation, mucous clearance and pulmonary damage. Although microbial community and inflammation have a very important role in respiratory diseases, few is known in bronchiectasis. The aim of this PhD project was to evaluate sputum microbiome and its interaction with the local host inflammatory response in adults with bronchiectasis during their stable state. Several studies were conducted to explore this research question. In the second chapter, we report the methodological selection of techniques for both microbiome and active neutrophil elastase (aNE) analysis in sputum. The third chapter is divided into three different sections. In the first, we identified two groups of adult bronchiectasis patients with different microbiome diversity levels. The low microbiome diversity group was found to be enriched in Pseudomonas, Staphylococcus and Streptococcus. Multivariate analysis identified FEV1%predict.<50, radiology and primary ciliary dyskinesia (PCD) to be independently associated with low microbiome diversity. The following section represents a preliminary study focused on bronchiectasis aetiologies, more specifically PCD and immunodeficiency. The study concerning PCD did not identify a clear association between aetiology, microbiome and inflammation comparing a group of matched PCD with idiopathic or post infective bronchiectasis, although, a trend could be observed.Subsequently, immunodeficiency was comparedto idiopathic bronchiectasis. These two groupsidentified, primary immunodeficiency and idiopathic differed in terms of alpha diversity and quantification of H. influenzae which was higher in the immunodeficiency group. Chapter fourfocuses on neutrophilic inflammation looking at the association of aNE in bronchiectasis with microbiome analysis. We found evidences of low microbiome diversity and P. aeruginosa identification in patients with high levels of aNE. The following study focused on active Cathepsin G (Cat-G) which is a putative biomarker for bronchiectasis. Cat-G was associated with disease severity, radiological severity, quality of life and chronic infection. It was also associated with low microbiome diversity and P. aeruginosa molecular detection. Finally, Cat-G and aNE resulted to be similar in predicting bronchiectasis severity (bronchiectasis severity index -BSI), severe exacerbation and chronic infection in bronchiectasis patients during stable state. Finally, in chapter five, we analyse microbiome and inflammation among adult bronchiectasis patients with chronic P. aeruginosa infection. Association network analysis identified differences in terms of number of interactions of Pseudomonas with other genera and interactions between cytokines and microbial effectors in patients with different exacerbations/year. We hope that this thesis may be a step forward in better understanding the role of both microbiome and inflammation in bronchiectasis that may lead to unravelling of endotypes and the identification of therapeutic targets. This will finally result in advances in a precise medicine approach for bronchiectasis patients

In silico evaluation of the thermal stress induced by MRI switched gradient fields in patients with metallic hip implant

This work focuses on the in silico evaluation of the energy deposed by MRI switched gradient fields in bulk metallic implants and the consequent temperature increase in the surrounding tissues. An original computational strategy, based on the subdivision of the gradient coil switching sequences into sub-signals and on the time-harmonic electromagnetic field solution, allows to realistically simulate the evolution of the phenomena produced by the gradient coils fed according to any MRI sequence. Then, Pennes' bioheat equation is solved through a Douglas-Gunn time split scheme to compute the time-dependent temperature increase. The procedure is validated by comparison with laboratory results, using a component of a realistic hip implant embedded within a phantom, obtaining an agreement on the temperature increase better than 5%, lower than the overall measurement uncertainty. The heating generated inside the body of a patient with a unilateral hip implant when undergoing an Echo-Planar Imaging (EPI) MRI sequence is evaluated and the role of the parameters affecting the thermal results (body position, coil performing the frequency encoding, effects of thermoregulation) is discussed. The results show that the gradient coils can generate local increases of temperature up to some kelvin when acting without radiofrequency excitation. Hence, their contribution in general should not be disregarded when evaluating patients' safety

Structural characterization of phytotoxic terpenoids from Cestrum parqui.

Isolation, chemical characterization and phytotoxicity of nine polyhydroxylated terpenes (five C13 nor-isoprenoids, two sesquiterpenes, a spirostane and a pseudosapogenin) from Cestrum parqui LHerr are reported. In this work we completed the phytochemical investigation of the terpenic fraction of the plant and described the structural elucidation of polar isoprenoids using NMR methods. All the configurations of the compounds have been assigned by NOESY experiments. Four new structures have been identified as (3S,5R,6R,7E,9R)-5,6,9-trihydroxy-3-isopropyloxy-7-megastigmene, 5a-spirostan-3b,12b,15a-triol, and 26-O-(30-isopentanoyl)-b-Dglucopyranosyl- 5a-furost-20(22)-ene-3b,26-diol, and as an unusual tricyclic sesquiterpene. The compounds have been assayed for their phytotoxicity on lettuce at the concentrations ranging between 104 and 107 M. The activities of some compounds were similar to that of the herbicide pendimethalin

Optic nerve sheath diameter ultrasound evaluation in intensive care unit. possible role and clinical aspects in neurological critical patients' daily monitoring

Background. The increase of the optic nerve sheath diameter (ONSD) is a reliable, noninvasive sonographic marker of intracranial hypertension. Aim of the study was to demonstrate the efficacy of ONSD evaluation, when monitoring neurocritical patients, to early identify malignant intracranial hypertension in patients with brain death (BD). Methods. Data from ultrasound ONSD evaluation have been retrospectively analyzed in 21 sedated critical patients with neurological diseases who, during their clinical course, developed BD. 31 nonneurological controls were used for standard ONSD reference. Results. Patients with neurological diseases, before BD, showed higher ONSD values than control group (CTRL: RT  cm; LT  cm; pre-BD: RT  cm; LT  cm; ) even without intracranial hypertension, evaluated with invasive monitoring. ONSD was further significantly markedly increased in respect to the pre-BD evaluation in neurocritical patients after BD, with mean values above 0.7 cm (RT  cm; LT  cm; ), with a corresponding dramatic raise in intracranial pressure. Logistic regression analysis showed a strong correlation between ONSD and ICP ( 0,895, ). Conclusions. ONSD is a reliable marker of intracranial hypertension, easy to be performed with a minimal training. Routine ONSD daily monitoring could be of help in Intensive Care Units when invasive intracranial pressure monitoring is not available, to early recognize intracranial hypertension and to suspect BD in neurocritical patients

Thermal Analysis of Human Tissues Exposed to Focused Beam THz Radiations

The thermal response of human tissues exposed to a focused beam terahertz electromagnetic radiation is evaluated through a combined analytical electromagnetic wave solution and a step-by-step finite element numerical model, which solves Pennes’ bioheat equation. The computational procedure is applied to a three-layer model of the human tissues for wave frequencies ranging from 0.025 THz to 1 THz and compared with a more detailed five-layer model. The effects of the Gaussian beam parameters of the electromagnetic radiation on the temperature elevation are finally evaluated

Dynamic Simulation of a Fe-Ga Energy Harvester Prototype Through a Preisach-Type Hysteresis Model

This paper presents the modeling of an Fe–Ga energy harvester prototype, within a large range of values of operating parameters (mechanical preload, amplitude and frequency of dynamic load, electric load resistance). The simulations, based on a hysteretic Preisach-type model, employ a voltage-driven finite element formulation using the fixed-point technique, to handle the material nonlinearities. Due to the magneto–mechanical characteristics of Fe–Ga, a preliminary tuning must be performed for each preload to individualize the fixed point constant, to ensure a good convergence of the method. This paper demonstrates how this approach leads to good results for the Fe–Ga prototype. The relative discrepancies between experimental and computational values of the output power remain lower than 5% in the entire range of operating parameters considered

Uncertainty propagation in phaseless electric properties tomography

Uncertainty propagation in a phaseless magnetic resonance-based electric properties tomography technique is investigated using the Monte Carlo method. The studied inverse method, which recovers the electric properties distribution at radiofrequency inside a scatterer irradiated by the coils of a magnetic resonance imaging scanner, is based on the contrast source inversion technique adapted to process phaseless input data.Comment: 4 pages, 6 figures. 2019 International Conference on Electromagnetics in Advanced Applications (ICEAA

Efficient prediction of MRI gradient-induced heating for guiding safety testing of conductive implants

PurposeTo propose an efficient numerical method to predict the temperature increase of an implantable medical device induced by any linearly polarized homogeneous magnetic field, according to the ISO 10974 methodology for testing of gradient-induced device heating. Theory and MethodsThe concepts of device-specific power and temperature tensors are introduced to mathematically describe the electromagnetic and thermal anisotropic behavior of the device, from which the device heating for an arbitrary exposure direction can be predicted. The proposed method is compared to a brute-force approach based on simulations, and validated by applying it to four reference orthopedic implants with a commercial simulation software. ResultsThe proposed method requires about 5%$$\%$$ of the time required by the brute-force approach, and 30%$$\%$$ of the memory occupancy. The temperature increase predicted by the proposed method over a range of incident magnetic field exposures deviated from brute-force direct simulations by less than &amp; PLUSMN;$$\pm$$0.3%$$\%$$. ConclusionThe proposed method allows efficient prediction of the heating of an implantable medical device induced by any linearly polarized homogeneous magnetic field using a small fraction of the simulations required by the brute-force approach. The results can be used to predict the worst-case orientation of the gradient field, for subsequent experimental characterization according to the ISO 10974 standard

Modeling analysis of the electromagnetic braking action on rotating solid cylinders

AbstractThe electromagnetic diffusion and the electromechanical phenomena arising in a solid cylinder rotating inside a magnetic field are here analyzed. The study is developed through a time stepping Finite Element voltage-driven formulation, employing the sliding mesh technique for handling the cylinder motion. The influence on the dynamic behavior and energy dissipation of the material electric and magnetic properties, the geometrical parameters and the supply conditions is investigated considering a model problem

Italian Wikipedia and epilepsy: an infodemiological study of online information-seeking behavior

Wikipedia is the most commonly accessed source of health information by both healthcare professionals and the lay public worldwide. We aimed to evaluate information-seeking behavior of Internet users searching the Italian Wikipedia for articles related to epilepsy and its treatment. Using Pageviews Analysis, we assessed the total and mean monthly views of articles from the Italian Wikipedia devoted to epilepsy, epileptic syndromes, seizure type, and antiepileptic drugs (AEDs) from January 1, 2015 to October 31, 2017. We compared the views of the article on epilepsy with those of articles focusing on Alzheimer's disease, migraine, multiple sclerosis, syncope, and stroke and adjusted all results for crude disease prevalence. With the only exception of the article on multiple sclerosis, the adjusted views for the Italian Wikipedia article on epilepsy were higher than those for the other neurological disorders. The most viewed articles on seizure type were devoted to tonic-clonic seizure, typical absence seizure, tonic convulsive seizures, and clonic convulsive seizures. The most frequently accessed articles on epilepsy syndromes were about temporal lobe epilepsy and Lennox-Gastaut syndrome. The most frequently viewed articles on AEDs were devoted to valproic acid, carbamazepine, and levetiracetam. Wikipedia searches seem to mirror patients' fears and worries about epilepsy more than its actual epidemiology. The ultimate reasons for searching online remain unknown. Epileptologists and epilepsy scientific societies should make greater efforts to work jointly with Wikipedia to convey more accurate and up-to-date information about epilepsy