Search

Additional file 1.

This study compared three severity measures for chronic rhinosinusitis with nasal polyps (CRSwNP). The outcome was to identify patients who are eligible for biological therapy.330 adult patients with CRSwNP were examined. Nasal polyp score (NPS), sinonasal outcome test (SNOT-22) and clinical-cytological grading (CCG) were compared. Clinical history, past surgery and asthma control test were also considered.Only 45 (13.6%) patients had a contextual positivity to the three severity measures. The concordance among tests was slight/fair. Patients with severe disease (all tests positive) had more impaired parameters. The mixed cytotype (OR = 4.07), nasal obstruction (OR = 10.06), post-nasal drip (OR = 1.98), embarrassment (OR = 2.53) and difficulty falling asleep (OR = 1.92) were significantly associated with severe CRSwNP.To identify candidates for biological therapy, the contextual use of NPS, SNOT-22 and CCG is preferable. In this way, global assessment of CRSwNP, including morphology, inflammation, comorbidity, symptoms and quality of life is possible.Rinosinusite cronica con poliposi nasale: come individuare i candidati alla terapia biologica nella pratica clinica.Questo studio confrontava 3 differenti indici di gravità della rinosinusite cronica con poliposi nasale (RSCcPN). L’obbiettivo era individuare i pazienti eleggibili al trattamento con farmaci biologici.330 pazienti adulti con RSCcPN erano arruolati. Tutti i pazienti venivano valutati mediante nasal polyp score (NPS), sinonasal outcome test (SNOT-22) e clinical-cytological grading (CCG). Inoltre erano considerati la storia clinica, i pregressi interventi chirurgici ed il controllo dell’asma.Solamente 45 (13,6%) pazienti avevano i 3 indici positivi. La concordanza tra i 3 indici era bassa/modesta. I pazienti con la malattia grave (contestuale positività a tutti i test) avevano peggiori parametri. Il citotipo misto (OR = 4,07), l’ostruzione nasale (OR = 10,06), il post-nasal drip (OR = 1,98), il disagio (OR = 2,53), e la difficoltà ad addormentarsi (OR = 1,92) erano significativamente associati con la malattia grave.È preferibile utilizzare contemporaneamente i 3 test per individuare i pazienti candidati alla terapia biologica. In questo modo si può avere un quadro generale della malattia, comprendente la morfologia dei polipi, lo stato di infiammazione, le comorbidità, i sintomi e la qualità della vita.

Chronic rhinosinusitis (CRS) includes two main phenotypes: without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP). CRSwNP may be associated with comorbidity, mainly concerning asthma, aspirin intolerance, and allergy. CRSwNP patients may also be evaluated by clinical-cytological grading (CCG). The current study investigated the prevalence and characteristics of the different CCG and phenotypes in CRSwNP outpatients examined in clinical practice. This retrospective cross-sectional study enrolled 791 consecutive CRSwNP outpatients (424 males, mean age 48.8 years). In the total population, asthma was a common comorbidity (30.8%) as well as aspirin intolerance (24.8%), and allergy (50.8%). As concerns CCG-grading, 210 (26.5%) outpatients had low-grade, 366 (46.3%) medium, and 215 (27.2%) high. As regards cytological phenotypes, 87 (11%) had neutrophilic type, 371 (46.3%) eosinophilic, 112 (14.2%) mast cell, and 221 (27.9%) mixed. High-grade CCG was significantly associated with more frequent asthma, aspirin intolerance, allergy, recurrent surgery, and mixed cytological phenotype. Low-grade CCG was characterized by fewer comorbidities and operations, and neutrophilic phenotype. Therefore, the present study confirmed that CCG is a useful tool in the management of outpatients with CRSwNP. CRSwNP is frequently associated with asthma, aspirin intolerance, and allergy comorbidity. High-grade CCG is frequently characterized by a mixed cytological phenotype, thus, by more severe progress. These real-world outcomes underline that CRSwNP deserves adequate attention for careful management and optimal identification of the best-tailored therapy; CCG and cytological phenotyping could be fruitful tools in clinical practice. Asthma and aspirin intolerance should be adequately investigated in all CRS patients.

This book represents the most current, comprehensive, and authoritative study of integrins on the market today. It provides an overview of the diverse biological functions of integrins, including: The structure and functions of integrin cytoplasmic domains, the role of b2 integrins in leukocyte adhesion, the role of platelet membrane fibrinogen receptor glycoprotein IIb-IIIa (aIIbb3) in thrombosis and hemostasis, the functions of aV integrin family, the role of integrins in signal transduction, the role of integrins in carcinoma cells, the role of integrins in internalization of microbial pathogens through the binding of Yersinia pseudotuberculosis invasin protein, the role of integrins in the skin, the integrin function in early vertebrate development using amphibian embryos.

Mycotoxines are widespread toxic substances produced by moulds in human and animal foodstuffs. Some of them, such as aflatoxin B1 (AFB1), are very toxic even in small amounts, but the modern approach to the problem (and the link with public health) started only in the 60s. The presence of aflatoxin M1 (AFM1), in milk and dairy products is also a problem of crucial interest. AFM1 is resistant to thermal and chemical treatments, so mineral sorbents are highly advisable. Clay minerals are suitable, but only a few data are available, as most studies deal with AFB1 (absent in milk). The capacity of clay materials to remove or attenuate the contamination of AFM1 in bovine milk was studied, also considering the effects of these clays on the nutritional properties of milk (in terms of protein, fat and lactose). In order to make the experiments transferable for practical use, only clays available from the market were tested, as well a very simple clay-milk interaction procedure was used. Some bentonites and a kaolin were selected for the experimental work. In particular, different bentonites were selected in order to partially accomplish the wide crystal-chemical features of smectite. Kaolin was less effective than bentonites, but was still able to detoxify contaminated milk, even using a little amount of kaolin (2.4% of the milk suspension). The detoxification role of the bentonites used was variable, but still very efficient: contaminated bovine milk (up to about 80 ng/L) was purified to safe levels (50ng/L for adults and 25ng/L for lactants), with moderate alteration of the nutritional properties of milk; moreover, the bentonite residue in the purified milk was very low (0.4%). The protein was more sensitive to clay adsorption compared to fat and lactose, and the decrease of protein in the treated milk increased with the clay-milk ratio. Among bentonites (beidellite-montmorillonite, ferruginous and saponite types), a saponite clay showed the highest sorbent capacity, in agreement with theoretical consideration about its higher cell surface (available for AFM1) and higher hydrophobicity. Isothermal adsorption procedures for the two more effective bentonites were also carried out in water. The collected data show an effective and safe use of clays in the detoxification of milk (and dairy products) contaminated by AFM1. The climatic changes observed in the last decades point to a wider diffusion of mycotoxines and health effects, and push toward the search for safe, cheap and accessible food treatments.

This paper deals with the numerical and experimental activities performed by CIRA for the Aeroelastic flutter predictions and the numerical structural model validation of the CIRA Unmanned Space Vehicle in the first phase of the Dropped Transonic Test campaign. Starting from the FE model, the numerical results have been used in order to plan the test strategy and to find the optimal location for sensors and shakers, allowing the optimal control and observation of the structural modes in the frequency range of interest. A dedicated suspension system has been designed and realized in order to achieve the test article free free boundary conditions. The Ground Vibration test has been carried out in order to characterize the experimental dynamic model of the vehicle by using both the Phase Resonance (Normal Mode) and the Phase Separation techniques. A correlation analysis between the experimental modal data and the numerical results has been performed. The aeroelastic model has been updated on the basis of experimental FRFs and modal parameters, by minimizing the discrepancies between the FE model predictions and experimental data. Finally the validated numerical model has been used to investigate the aeroelastic phenomena. The interactions of elastic, inertial and aerodynamic forces have been predicted and the flutter speeds have been calculated.

Tissue remodelling is a dynamic process that occurs during fetal or adult life and involves a modification of the original organization and function of a tissue. Tissue remodelling is observed in physiological and pathological conditions such as during wound healing or in the mammary gland during the course of pregnancy. In this review we will discuss the remodelling occurring in the liver as a consequence of chronic inflammation, as observed in chronic hepatitis, or as a consequence of hepatocellular carcinoma (HCC) progression in more detail. We will consider how altered deposition and turn-over of extracellular matrix (ECM) proteins could lead to development of liver fibrosis, and how the exacerbation of fibrosis could underlie the development of cirrhosis. The involvement of inflammatory and anti-inflammatory cytokines commonly used as therapeutic agents, such as Interferon-a, is then evaluated with a particular focus on modulation of ECM proteolysis. Finally, we analyze the role of alterations of the surrounding microenvironment including ECM, growth factors, cytokines and membrane receptors for ECM ligands in the development of HCC and in its invasive behaviour.

Laminin 5 (alpha3beta3gamma2) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-alpha3, -beta3, and -gamma2 mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma restricted to the medullary area on a subset of stellate epithelial cells and vessel structures. We also found that laminin 5 may influence mature human thymocyte expansion; while bulk laminin and laminin 2, when cross-linked, are comitogenic with a TCR signal, cross-linked laminin 5 has no effect. By contrast, soluble laminin 5 inhibits thymocyte proliferation induced by a TCR signal. This is accompanied by a particular pattern of inhibition of early tyrosine kinases, including Zap 70 and p59(fyn) inhibition, but not overall inhibition of p56(lck). Using a mAb specific for alpha6beta4 integrins, we observed that while alpha3beta1 are known to be uniformly present on all thymocytes, alpha6beta4 expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and alpha6beta4 on mature thymocytes. Moreover, the soluble Ab against alpha6beta4 inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that alpha6beta4 is involved in laminin 5-induced modulation of T cell activation.Laminin 5 (alpha3beta3gamma2) distribution in the human thymus was investigated by immunofluorescence on frozen sections with anti-alpha3, -beta3, and -gamma2 mAbs. In addition to a linear staining of subcapsular basal laminae, the three mAbs give a disperse staining in the parenchyma restricted to the medullary area on a subset of stellate epithelial cells and vessel structures. We also found that laminin 5 may influence mature human thymocyte expansion; while bulk laminin and laminin 2, when cross-linked, are comitogenic with a TCR signal, cross-linked laminin 5 has no effect. By contrast, soluble laminin 5 inhibits thymocyte proliferation induced by a TCR signal. This is accompanied by a particular pattern of inhibition of early tyrosine kinases, including Zap 70 and p59(fyn) inhibition, but not overall inhibition of p56(lck). Using a mAb specific for alpha6beta4 integrins, we observed that while alpha3beta1 are known to be uniformly present on all thymocytes, alpha6beta4 expression parallels thymocyte maturation; thus a correspondence exists between laminin 5 in the thymic medulla and alpha6beta4 on mature thymocytes. Moreover, the soluble Ab against alpha6beta4 inhibits thymocyte proliferation and reproduces the same pattern of tyrosine kinase phosphorylation suggesting that alpha6beta4 is involved in laminin 5-induced modulation of T cell activation.