Allergic Sensitization in Rhinitis and Asthma

Allergic rhinitis (AR) is usually defined as an inflammatory disease of the nasal mucosa induced by an interaction of environmental allergens and IgE in sensitized patients. Its symptoms are sneezing, nasal itching, rhinorrhoea and nasal obstruction. Allergic rhinitis affects approximately 20- 30% of the population worldwide and its prevalence is increasing. Isolated AR is rare and it actually has to be considered as a systemic allergic disease, associated to comorbidities, such as conjunctivitis, chronic middle ear effusions, irregular sleep, sinusitis, lymphoid hypertrophy with obstructive sleep apnoea. The most relevant comorbidity is asthma, a heterogeneous disease, usually characterized by chronic airway inflammation in which many cells and cellular elements play an important role. Bronchial asthma is characterized by bronchial hyper-reactivity and symptoms may be triggered or worsened by factors such as viral infections, allergens, tobacco smoke, exercise and stress. A state of "minimal persistent inflammation" is permanently maintained in the lower respiratory tract of asthmatic individuals. The diagnosis of asthma is based on evidence of variable airflow limitation tested with spirometry and a positive bronchodilation reversibility test. Skin prick tests (SPTs) are widely used to demonstrate an immediate IgE-mediated allergic reaction. They represent a major diagnostic tool in the field of allergy. Skin prick tests have a high specificity and sensitivity for the diagnosis of inhalant allergens. Immunotherapy (AIT) for allergic diseases has entered in a new age characterized by the development of a few innovative therapeutic classes of standardized allergen formulations registered. Clinical randomized trials have demonstrated the efficacy of AIT in allergic rhinitis in children and in adults, expressed in terms of reduction of symptom score and use of rescue medication. The efficacy is confirmed both for subcutaneous (SCIT) and sublingual (SLIT) immunotherapy in adults and in pediatric patients. The long lasting effect of AIT after its discontinuation is an important added value of this therapy. Controlled studies are available, where the carry-over effect of AIT is demonstrated for two years after discontinuance. The capacity to prevent new sensitizations, and to modify the evolution of the disease from the rhinitis to asthma are two important features of AIT. Allergen immunotherapy showed preventive capacity and also a carryover effect once treatment is discontinued

A flexible scintillation light apparatus for rare event searches

Compelling experimental evidences of neutrino oscillations and their implication that neutrinos are massive particles have given neutrinoless double beta decay a central role in astroparticle physics. In fact, the discovery of this elusive decay would be a major breakthrough, unveiling that neutrino and antineutrino are the same particle and that the lepton number is not conserved. It would also impact our efforts to establish the absolute neutrino mass scale and, ultimately, understand elementary particle interaction unification. All current experimental programs to search for neutrinoless double beta decay are facing with the technical and financial challenge of increasing the experimental mass while maintaining incredibly low levels of spurious background. The new concept described in this paper could be the answer which combines all the features of an ideal experiment: energy resolution, low cost mass scalability, isotope choice flexibility and many powerful handles to make the background negligible. The proposed technology is based on the use of arrays of silicon detectors cooled to 120 K to optimize the collection of the scintillation light emitted by ultra-pure crystals. It is shown that with a 54 kg array of natural CaMoO4 scintillation detectors of this type it is possible to yield a competitive sensitivity on the half-life of the neutrinoless double beta decay of 100Mo as high as ~10E24 years in only one year of data taking. The same array made of 40CaMoO4 scintillation detectors (to get rid of the continuous background coming from the two neutrino double beta decay of 48Ca) will instead be capable of achieving the remarkable sensitivity of ~10E25 years on the half-life of 100Mo neutrinoless double beta decay in only one year of measurement.Comment: 12 pages, 4 figures. Prepared for submission to EPJ

Cysticercosis by Taenia pisiformis in Brown Hare (Lepus europaeus) in\ua0Northern Italy: Epidemiologic and pathologic features

In Northern Italy, a hastening of hare population decline was noticeable from 2008. In the same year hunters reported a sudden increase of hares infected by Taenia sp. larvae, whose morphology was consistent with T. pisiformis cysticerci. The aim of the survey was: i)to identify the parasites through morphological features and molecular techniques; ii)to quantify the prevalence and abundance of cysticerci in hunted hares; iii)to describe pathological aspects of parasite-induced lesions; iv)to evaluate the short-term trend of the infection comparing two different hunting seasons; v)to highlight possible relationship between T. pisiformis infection and hare-related variables. In 2013, 2015 the viscera of 54 and 61 hares legally hunted in agro-ecosystems of the Po Plain were collected. Peritoneum, liver and lungs were examined for cysticercosis; abundance was estimated counting superficial parasites in liver; parasites were microscopically identified by shape and measure of both large and small hooks. One cysticercus from each hare was analized by a PCR targeting Taeniid species and then sequenced. Frozen liver, lungs and gastrointestinal peritoneum were macroscopically observed and, after thawing, representative samples from the available organs were collected for histologic examination to verify parasitic cysts and the subsequent damage of the involved organs. Sex, weight and age class of the animals were recorded. Generalized linear models were used for statistical analysis. T. pisiformis was isolated in 8 hares in 2013 (prevalence 14.8%; abundance range: 0-400; mean abundance 17.8) and in 2 hares in 2015 (prevalence 3.28%; abundance range: 0-180; mean abundance 3.22). Identification was confirmed morphologically and by PCR. The DNA sequencing confirmed T. pisiformis in all samples. The sequences were all identical each-other. Infection was significantly related with adult age class, sampling year and low full-weight. Epidemiological and pathological pattern suggest both a possible role on host population health and a tendency toward host-parasite equilibrium

3D Printing Cardiovascular Anatomy: A Single-Centre Experience

This chapter presents the experience of the cardiac engineering team within the Centre for Cardiovascular Imaging at Great Ormond Street Hospital for Children (London, UK) in using three-dimensional (3D) printing technology. 3D models can serve different functions towards implementing a patient-specific approach for studying and potentially treating congenital heart disease (CHD). In order to showcase different potential applications, this chapter discusses not only clinical case studies and engineering experiments but also the potential for translation through patients and public involvement and engagement (PPI/E)

First report outside Eastern Europe of West Nile virus lineage 2 related to the Volgograd 2007 strain, northeastern Italy, 2014

open11noWest Nile virus (WNV) is a Flavivirus transmitted to vertebrate hosts by mosquitoes, maintained in nature through an enzootic bird-mosquito cycle. In Europe the virus became of major public health and veterinary concern in the 1990s. In Italy, WNV re-emerged in 2008, ten years after the previous outbreak and is currently endemic in many areas of the country. In particular, the northeastern part of Italy experience continuous viral circulation, with human outbreaks caused by different genovariants of WNV lineage 1, Western-European and Mediterranean subcluster, and WNV lineage 2, Hungarian clade. Alongside the WNV National Surveillance Program that has been in place since 2002, regional surveillance plans were implemented after 2008 targeting mosquitoes, animals and humans.openRavagnan, Silvia; Montarsi, Fabrizio; Cazzin, Stefania; Porcellato, Elena; Russo, Francesca; Palei, Manlio; Monne, Isabella; Savini, Giovanni; Marangon, Stefano; Barzon, Luisa; Capelli, GioiaRavagnan, Silvia; Montarsi, Fabrizio; Cazzin, Stefania; Porcellato, Elena; Russo, Francesca; Palei, Manlio; Monne, Isabella; Savini, Giovanni; Marangon, Stefano; Barzon, Luisa; Capelli, Gioi

Finite Element Analysis to Study Percutaneous Heart Valves

Communications engineering / telecommunication

Computational investigation of the haemodynamics shows criticalities of central venous lines used for chronic haemodialysis in children

Background: Haemodialysis is a life-saving treatment for children with kidney failure. The majority of children have haemodialysis through central venous lines (CVLs). The use of CVLs in pediatric patients is often associated to complications which can lead to their replacement. The aim of this study is to investigate haemodynamics of pediatric CVLs to highlight the criticalities of different line designs. Methods: Four models of CVLs for pediatric use were included in this study. The selected devices varied in terms of design and sizes (from 6.5 Fr to 14 Fr). Accurate 3D models of CVLs were reconstructed from high-resolution images including venous and arterial lumens, tips and side holes. Computational fluid dynamics (CFD) analyses were carried out to simulate pediatric working conditions of CVLs in ideal and anatomically relevant conditions. Results: The arterial lumens of all tested CVLs showed the most critical conditions with the majority of blood flowing through the side-holes. A zone of low flow was identified at the lines' tip. The highest shear stresses distribution (>10 Pa) was found in the 8 Fr line while the highest platelet lysis index in the 10 Fr model. The analysis on the anatomical geometry showed an increase in wall shear stress measured in the 10 F model compared to the idealised configuration. Similarly, in anatomical models an increased disturbance and velocity of the flow was found inside the vein after line placement. Conclusion: This study provided a numerical characterization of fluid dynamics in pediatric CVLs highlighting performance criticalities (i.e. high shear stresses and areas of stagnation) associated to specific sizes (8 Fr and 10 Fr) and conditions (i.e. anatomical test)

Metadynamics Simulations Distinguish Short- and Long-Residence-Time Inhibitors of Cyclin-Dependent Kinase 8.

The duration of drug efficacy in vivo is a key aspect primarily addressed during the lead optimization phase of drug discovery. Hence, the availability of robust computational approaches that can predict the residence time of a compound at its target would accelerate candidate selection. Nowadays the theoretical prediction of this parameter is still very challenging. Starting from methods reported in the literature, we set up and validated a new metadynamics (META-D)-based protocol that was used to rank the experimental residence times of 10 arylpyrazole cyclin-dependent kinase 8 (CDK8) inhibitors for which target-bound X-ray structures are available. The application of reported methods based on the detection of the escape from the first free energy well gave a poor correlation with the experimental values. Our protocol evaluates the energetics of the whole unbinding process, accounting for multiple intermediates and transition states. Using seven collective variables (CVs) encoding both roto-translational and conformational motions of the ligand, a history-dependent biasing potential is deposited as a sum of constant-height Gaussian functions until the ligand reaches an unbound state. The time required to achieve this state is proportional to the integral of the deposited potential over the CV hyperspace. Average values of this time, for replicated META-D simulations, provided an accurate classification of CDK8 inhibitors spanning short, medium, and long residence times