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It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

Study question Could Reactive Oxygen Species (ROS) detected in human spermatozoa represent a predictive marker of fertilization ability? Summary answer ROS detected by CellROX® Orange probe is related to a better sperm quality and function, indicating the sensitivity of the probe to identify physiological ROS. What is known already Oxidative stress (OS), defined as an unbalance between ROS production and antioxidant defenses, is one of the causes of male infertility. A small amount of ROS is necessary for the physiological sperm function, however high ROS levels could impair fertility potential inducing damages at membrane, protein and DNA levels. Previous studies performed by using different methods and probes for OS evaluation in semen or in spermatozoa highlighted the negative role of ROS on sperm functions. However, such studies were not conclusive because of the small number of included subjects and of high variability in the cohorts. Study design, size, duration Observational study conducted on 73 male partners of infertile couples attended consecutively to the Andrology Laboratory of Careggi University Hospital of Florence from September to December 2021. Analyses were performed on both washed and Swim-up selected spermatozoa. Participants/materials, setting, methods After routine semen analysis, washed and Swim-up selected spermatozoa were incubated with CellRox®Orange (a fluorescent probe able to reveal OS in viable cells), at the concentration of 1 µM for 30 minutes at 37°C, 5%CO2, and revealed by flow cytometry. Sperm DNA fragmentation (by TUNEL/PI method), sperm kinematic parameters and hyperactivated motility (by C.A.S.A. system) were also assessed. In some samples a double staining with CellRox®Orange and Annexin V (which stains phosphatidylserine externalization) was performed. Main results and the role of chance We found that the percentage of spermatozoa positive to CellRox® Orange is positively correlated with routine seminal parameters. Although this result appears in contrast with most studies in literature reporting negative correlations between OS and semen parameters, it can be explained by the fact that the probe is specific for viable spermatozoa characterized by a better motility and morphology. Considering the importance of distinguishing between positive and negative ROS in spermatozoa, we further investigated the significance of ROS detected by this probe. To understand whether the probe marks spermatozoa with a better quality, CellRox® Orange positivity was evaluated in Swim-up selected spermatozoa finding significantly higher levels of CellRox® Orange positivity respect to unselected samples. Furthermore, the fact that most of the CellRox® Orange positive spermatozoa were negative for Annexin V (which reveals cells with early signs of apoptosis) is a further confirmation of the good quality of CellRox® Orange positive spermatozoa. Another evidence is represented by the finding that we observed a negative correlation between OS detected by CellRox® Orange and sperm DNA fragmentation, although several studies have shown a positive relationship between these two parameters (when OS is measured by different probes). Limitations, reasons for caution Up to now, the study involved a limited number of subjects. Further experiments should be performed to increase the number of subjects in order to confirm the results. Wider implications of the findings Results of this study together with those previously published evidence that different OS is detected depending on which probe is used. CellRox® Orange seems to be sensible for physiological ROS detection, therefore, it could be employed in future studies aimed to evaluate the association between OS and assisted reproduction outcomes. Trial registration number not applicable

BackgroundInterstitial lung disease (ILD) is a common manifestation of systemic sclerosis and other Rheumatic Diseases, and is one of the major causes of mortality. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and anti-inflammatory effects in preclinical models of systemic sclerosis and ILD.ObjectivesTo evaluate efficacy and safety of Nintedanib in pulmonary fibrosis secondary to Connective Tissue Disease.MethodsTen patients with pulmonary fibrosis secondary to Connective Tissue Disease treated with Nintedanib were monitored at baseline, 6 and/or 12 months, with clinical assessment, chest CT scan and/or pulmonary function testing (PFT) with assessment of the diffusing capacity for CO (DLCO). 8/10 patients had a diagnosis of Progressive Systemic Sclerosis, while the remaining ones had Polydermatomyositis and Mixed Connectivitis. All patients were dyspnoic at baseline and presented with dry cough. All patients had pulmonary fibrosis according to high-resolution chest CT scan. All patients had been treated with at least one csDMARD or bDMARD (cyclophosphamide, azathioprine, cyclosporine, rituximab, tocilizumab), prior to receiving nintedanib. At baseline 2/10 patients were treated with Nintedanib monotherapy, 7/10 were in combination therapy with Mycophenolate, 1 patient received a combination therapy with cyclosporine.ResultsCompared to baseline values, 4/7 patients showed stationarity of the respiratory function parameters (DLCO), in 2/7 patients it was observed a significant improvement of the DLCO (with a change of 15%) while in only 1 patient there was a worsening over time. FVC remained stable over time except in 1 patient who got a significant improvement. In 5/9 patients cough improved (unchanged in the rest of patients). Dyspnea (NYHA scale) improved in 6/9 patients, remained stationary in 2/6 patients and became worse in 1 patient. 8/9 patients had a stable chest CT at 6 and / or 12 months, while only 1 patient witnessed a further worsening of the fibrosis. 50% of the patients showed good gastrointestinal tolerance to the full dose of nintedaninb. The other half had the dose reduced in order to improve gastrointestinal symptoms.ConclusionOur data show that patients with ILD associated with Rheumatic Diseases treated with nintedanib had a clinical benefit over dyspnea and cough symptoms and a stabilization of radiological findings 12 months after starting the treatment. Also, respiratory function parameters remained stable over time. Gastrointestinal adverse events, including diarrhea, were common in these patients, but therapeutic dose adjustment led to fast symptoms resolution and good tolerance.References[1]Kristin B Highland, Oliver Distler, Masataka Kuwana, Yannick Allanore, Shervin Assassi, Arata Azuma, Arnaud Bourdin, Christopher P Denton, Jörg H W Distler, Anna Maria Hoffmann-Vold, Dinesh Khanna, Maureen D Mayes, Ganesh Raghu, Madelon C Vonk, Martina Gahlemann, Emmanuelle Clerisme-Beaty, Mannaig Girard, Susanne Stowasser, Donald Zoz, Toby M Maher, SENSCIS trial investigators. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial. Lancet Respir Med. 2021 Jan;9(1):96-106.[2]Oliver Distler, Kristin B Highland, Martina Gahlemann, Arata Azuma, Aryeh Fischer, Maureen D Mayes, Ganesh Raghu, Wiebke Sauter, Mannaig Girard, Margarida Alves, Emmanuelle Clerisme-Beaty, Susanne Stowasser, Kay Tetzlaff, Masataka Kuwana, Toby M Maher, SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528.Disclosure of InterestsNone declared

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z 1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at [Formula: see text] and [Formula: see text] with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

Major challenges in the area of wet transportation of radioactive materials are reliability and safety of transportation casks. In most cases, the bottom part of the cask is filled with water whereas a gaseous mixture is contained in the upper part. In such a configuration, water radiolysis leads to the formation of hydrogen and oxygen, which continuously enriches the gaseous mixture. Among the functions to be satisfied, wet transportation systems shall thus allow the control of the hydrogen content below its flammability limit. This is currently achieved by limiting the transportation duration so as to reopen the cask before the critical hydrogen concentration is reached. Development of new technologies that would mitigate the hydrogen risk is all the more motivated because it would allow an extension of the transportation duration. AREVA-TN International and the Institut de recherches sur la catalyse et l'environnement de Lyon have developed a catalytic system which aims at buffering the hydroge...

The efficacy of the dioxygenase inhibitor prohexadione-Ca (ProCa) as an inducer of resistance responses against apple scab (Venturia inaequalis/Spilocaea pomi) was evaluated in two sets of experiments under glasshouse conditions. ProCa (200 ppm) was applied on seedlings of open-pollinated Malus domestica L. cv. Golden Delicious, and 10 days after application, a group of seedlings was inoculated with a conidial suspension of S. pomi. Total RNA was extracted from leaf samples collected at different times from both inoculated and noninoculated seedlings, and expression of the pathogenesis-related proteins PR-1, PR-2, PR-5, PR-8, PR-10 and chitinase was studied by reverse transcription-polymerase chain reaction and Northern blot hybridisation. Disease severity was significantly lower on seedlings treated with ProCa than on the water-treated control seedlings. ProCa triggered a general increase in gene expression of almost all the PR genes; only the level of chitinase and PR-10 did not show a detectable increase. A strong upregulation of all the assayed genes was observed in leaves of apple seedlings first treated with ProCa and then inoculated with the pathogen, whereas no expression and/or a constitutive signal was found in samples from the control seedlings.

The first endpoint of this study was to find new markers that document the progression of hepatic steatosis through quantitative histomorphometric analysis in the absence of hemodynamic changes. The second endpoint was to start building a mathematical database to help to achieve a score in the future. For this study we enrolled 130 random patients, including 10 with normal histology despite suspected disease, 70 positive for steatosis, 20 affected by nonalcoholic steato hepatitis, and 30 with hepatitis virus C or B-related cirrhosis. One hundred thirty images were analyzed for a total of 1,320 sinusoids. Each image was processed with a custom program written with the use of the Vision toolbox of the Labview platform, following a semiautomated procedure. The mean sinusoidal areas (SAs) and percentage fractions of parenchymal area occupied by sinusoids (SA/PA) were subdivided into 3 groups. Finally, we analyzed the form of sinusoids, approximating them to an ellipse, to be able to define the relationship between the 2 axes with the aim of proposing a parameter, "local hydraulic resistance" (LHR), that was proportional to the resistance to blood flow within the bounds of the histologic specimen. Among the images, we observed a difference in the size of SAs among the 3 groups of patients, namely, normal, steatotic of different stages, and cirrhotic patients. In fact, there was evidence of a reducted SA when steatosis was30%, with an average value of 0.0032 mm(2), patients with steatosis of 30%-50% showed an average SA of 0.0024 mm(2), and there was a further reduction among subjects with steatosis grades50% (mean 0.0017 mm(2)). The LHR value showed that the morphometric parameter SA/PA could be quantitatively interpreted also as a functional impairment relative to the increased resistance opposing blood flow in pathologic conditions.

This paper considers the problem of the construction of nonlinear mapping by using an adaptive polynomial neural network [1], implementing a learning rule. First we apply the method to a two-class pattern recognition problem. We use one high order neuron with a threshold element ranging from −1 to +1. Positive output means class 1 and negative output means class 2. The main idea of the method proposed is that the weights are adjusted automatically in such a way to move the decision boundary to a place of low pattern density. Once reached the convergence, to improve the generalization ability, we add a growing noise to the data available. The training is performed by a steepest-descent algorithm on the weights.

This study had the following aims: to verify whether children living in different environmental areas present a different development degree of the functional prerequisites of psychomotricity; to test whether a targeted psychomotricity education program could favourably modify the potential differences which may be observed; to investigate the relationship, if any, between the anthropometric differences and the functional prerequisites of psychomotricity.One hundred and sixty-five Italian children, 83 males and 82 females, 6-7 years old were enrolled in this study. Based on the provenance area, the children were subdivided into two groups: the urban one (N=85) and the rural one (N=80). Both groups underwent an initial psychomotor assessment including standardised psychomotor tests aimed at evidencing the general dynamic coordination ability and the static and dynamic balance capacity of every child.The findings of this research point out that children living in an urban setting selectively showed a lower degree of balance development, if compared to children living in rural areas; a targeted psychomotor education program favourably modified the differences in the balance development between the two examined groups, up to their disappearance. In the urban group the body mass index had a trend towards a negative relationship with balance development.Children grown up in an urban environment showed a delay in balance development, if compared to children of the same age grown up in rural areas. This study also clearly proves that such a delay may be regained by means of a targeted psychomotor education program.

Microcalcifications (MCs) are of great importance in breast cancer early diagnosis and sometimes they do represent the unique evidence of cancer disease (up to 47%). Their visualization in ultrasound (US) is limited by a number of factors the most important of which are speckle and system limited spatial resolution. MCs are modelled as hydroxyapatite (HA) microgranules and sound scattering from HA microgranules can be solved by mean of Faran model. Agar based phantoms have been manufactured to simulate human soft tissues with cylindrical shape and a commercial echo-scanner (Technos Mpx di ESAOTE s.r.l., Genova, Italia) has been used to perform the scan of the phantom. This work concerns with phantoms and the analysis of US data for the visualization of HA microgranules under multiple angle scan. A reconstruction method was hence used to get a 2D map of reflectivity from the target and further Fourier analysis was applied to radio frequency (RF) data. (4 pages)

We show the simulation of neural networks on distributed-memory, message-passing multiprocessor systems, by means of a CSP language and related programming environment, that has been implemented at the University of Napoli. Among the features of the system, that make it suitable for simulation, and particularly for fast prototyping, of neural network models, are: simplicity, generality, portability, scalability and ease of use, at a good level of efficiency.

We consider a McCulloch and Pitts, also called Boolean, net in the Caianiello formalism, as a set of “node assemblies”, to implement an Hebbian rule [1]. So we obtain a system learning, by examples, how to control a robot in the execution of task sequences, without any limitation on their length.

41 hyaline membrane diseases (H.M.D.), 39 fetal aspiration syndromes (F.A.S.) and 81 wet lung syndromes (W.L.S.) observed during the last four years have been critically examined by the Authors. Anamnestic, clinic and radiological findings have revealed how it is difficult to make a differential diagnosis between W.L.S. and the two other neonatal respiratory disorders and therefore how it is difficult to classify the W.L.S. as an autonomous nosological entity. Therefore the AA. think that the neonatal respiratory disorders can be divided in only two groups: H.M.D. and F.A.S., and suggest the hypothesis that W.L.S. is not an autonomous nosological entity but may be only a milder clinic and radiological aspect of the two other syndromes.

The reported incidence of Bronchopulmonary dysplasia (BPD) varies from 5% to 68%. The different criteria used to define BPD are responsable for these discrepancies: some Authors include only patients with a clinical and radiological picture that fits the stage IV, as originally described by Northway, others use a more liberal approach and include all patients with manifestations of chronic pulmonary disease. We observed BPD in 12 of 22 (54%) survivors infants of very low birth weight (mean 1115 gm) and gestational age (mean 29,2 weeks). The infants were all born between November 1979 and March 1981. According to Ehrenkranz et al., we classified the radiological findings as severe, moderate and mild. We believe that the etiology of BPD in very low birth weight infants is multifactorial. However, pulmonary oxygen toxicity and immaturity are the most important causes.

The authors describe a case of hepatic hemangiomathosis in a three months old infant with a clinical picture of multiple cutaneous hemangioma, epatomegaly and severe cardiac failure. The cardiac catheterization with selective angiography showed extensive communication between the mammary artery and the hepatic circulation with the presence of large bloody areas into the markedly enlarged liver. The medical treatment with digitalis, diuretics, and corticosteroids obtained rapid resolution of the cardiac failure and of the A-V fistula signs. A clinical picture of severe liver cholostatic disease developed few months later which was confirmed by histological examination. The subsequent course has been favorable with complete clinical resolution of the liver disease.

The complete nucleotide sequence of the Bacillus coagulans plasmid pBC1 was determined. The sequence revealed an open reading frame encoding a polypeptide of 259 amino acids. This open reading frame shows sequence similarity to genes coding for replication-associated proteins in a group of gram-positive bacterial plasmids known to replicate via single-stranded intermediates. A region required for replication in cis, when the intact replicon is supplied in trans, was identified as well.

Bone quality is affected by trabecular architecture at microscopic level. Various abnormalities of bone tissue lead to altered strength and to an increased susceptibility to fracture, such as Osteoporosis and Osteoarthritis, two major health burdens of our society. These are two complex musculoskeletal diseases that mainly concern bone tissue. In the last twenty years, there has been a growing interest in finding an appropriate topological model for the micro-architecture of trabecular bone tissue. In particular, we prove that these models involve general topological spaces. The appropriate notion to deal with is that of CW-complex.

This paper presents a case study of the HVAC system for a greenhouse. The optimal control of greenhouse climate entails operations on the control variables in order to maximize the economic profit of the grower and is heavily influenced by the accuracy of the greenhouse dynamics and the weather predictions, thus accurate dynamic model and good weather forecasts are required. We first address the problem of environmental temperature forecasting by using a classical linear model. We then suggest superior nonlinear prediction models based on neural networks. Finally, an optimal control is applied to the nonlinear greenhouse model and is approximately implemented by means of neural networks. >