Showing papers by "University of Palermo published in 2017"

An assessment of the global impact of 21st century land use change on soil erosion.

Abstract: Human activity and related land use change are the primary cause of accelerated soil erosion, which has substantial implications for nutrient and carbon cycling, land productivity and in turn, worldwide socio-economic conditions. Here we present an unprecedentedly high resolution (250 × 250 m) global potential soil erosion model, using a combination of remote sensing, GIS modelling and census data. We challenge the previous annual soil erosion reference values as our estimate, of 35.9 Pg yr−1 of soil eroded in 2012, is at least two times lower. Moreover, we estimate the spatial and temporal effects of land use change between 2001 and 2012 and the potential offset of the global application of conservation practices. Our findings indicate a potential overall increase in global soil erosion driven by cropland expansion. The greatest increases are predicted to occur in Sub-Saharan Africa, South America and Southeast Asia. The least developed economies have been found to experience the highest estimates of soil erosion rates.

Parenting Stress, Mental Health, Dyadic Adjustment: A Structural Equation Model

Abstract: Objective: In the first year of the postpartum period, parenting stress, mental health, and dyadic adjustment are important for the wellbeing of both parents and the child. However, there are few studies that analyze the relationship among these three dimensions. The aim of this study is to investigate the relationships between parenting stress, mental health (depressive and anxiety symptoms), and dyadic adjustment among first-time parents. Method: We studied 268 parents (134 couples) of healthy babies. At 12 months postpartum, both parents filled out, in a counterbalanced order, the Parenting Stress Index-Short Form, the Edinburgh Postnatal Depression Scale, the State-Trait Anxiety Inventory, and the Dyadic Adjustment Scale. Structural equation modeling was used to analyze the potential mediating effects of mental health on the relationship between parenting stress and dyadic adjustment. Results: Results showed the full mediation effect of mental health between parenting stress and dyadic adjustment. A multi-group analysis further found that the paths did not differ across mothers and fathers. Discussion: The results suggest that mental health is an important dimension that mediates the relationship between parenting stress and dyadic adjustment in the transition to parenthood.

On-chip generation of high-dimensional entangled quantum states and their coherent control

Abstract: Optical quantum states based on entangled photons are essential for solving questions in fundamental physics and are at the heart of quantum information science. Specifically, the realization of high-dimensional states (D-level quantum systems, that is, qudits, with D > 2) and their control are necessary for fundamental investigations of quantum mechanics, for increasing the sensitivity of quantum imaging schemes, for improving the robustness and key rate of quantum communication protocols, for enabling a richer variety of quantum simulations, and for achieving more efficient and error-tolerant quantum computation. Integrated photonics has recently become a leading platform for the compact, cost-efficient, and stable generation and processing of non-classical optical states. However, so far, integrated entangled quantum sources have been limited to qubits (D = 2). Here we demonstrate on-chip generation of entangled qudit states, where the photons are created in a coherent superposition of multiple high-purity frequency modes. In particular, we confirm the realization of a quantum system with at least one hundred dimensions, formed by two entangled qudits with D = 10. Furthermore, using state-of-the-art, yet off-the-shelf telecommunications components, we introduce a coherent manipulation platform with which to control frequency-entangled states, capable of performing deterministic high-dimensional gate operations. We validate this platform by measuring Bell inequality violations and performing quantum state tomography. Our work enables the generation and processing of high-dimensional quantum states in a single spatial mode.

Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper

Abstract: The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge - of the nature of EV(-RNA)s and of how to effectively and reliably study them - currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data.

Guidelines for the use of flow cytometry and cell sorting in immunological studies

Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

Gaining insight into exclusive and common transcriptomic features linked with biotic stress responses in Malus.

Abstract: Identifying key information in transcriptomic data is very important, especially when the “omic” study deals with plant responses to stresses in field conditions where a high number of variables and disturbing factors may affect the analysis. In this meta-analysis we collected 12 transcriptomic works in Malus in order to identify which key genes, proteins, gene categories are involved in general plant pathological conditions and those features linked with exclusive biotic stress responses. Those genes that are only related with molecular responses to pathogen attacks and those linked with other plant physiological processes were identified. A pipeline composed by pathway and gene set enrichment analysis, protein-protein interaction networks and gene visualization tools was employed. A total of 13,230 genes of the 12 studies were analyzed with functional data mining tools: 5,215 were upregulated, 8,015 were downregulated. Gene set enrichment analysis pointed out that photosynthesis was inhibited by Erwinia amylovora and fungal pathogens. Different hormonal crosstalk was linked with responses to different pathogens. Gibberellin-related pathways, ABA-related were mostly repressed by fungal pathogens. Relating to transcription factors, genes encoding MYBs and WRKY2 were downregulated by fungal pathogens and 12 WRKYs were commonly regulated by different biotic stresses The protein-protein interaction analysis discovered the presence of several proteins affected by more than one biotic stress including a WRKY40 and some highly interactive proteins such as heat shock proteins. This study represents a first preliminary curated meta-analysis of apple transcriptomic responses to biotic stresses.

Transcriptional responses to pre-flowering leaf defoliation in grapevine berry from different growing sites, years, and genotypes

Abstract: Leaf removal is a grapevine canopy management technique widely used to modify the source-sink balance and/or microclimate around berry clusters to optimize fruit composition. In general, the removal of basal leaves before flowering reduces fruit set, hence achieving looser clusters, and improves grape composition since yield is generally curtailed more than proportionally to leaf area itself. Albeit responses to this practice seem quite consistent, overall vine performance is affected by genotype, environmental conditions, and severity of treatment. The physiological responses of grape varieties to defoliation practices have been widely investigated, and just recently a whole genome transcriptomic approach was exploited showing an extensive transcriptome rearrangement in berries defoliated before flowering. Nevertheless, the extent to which these transcriptomic reactions could be manifested by different genotypes and growing environments is entirely unexplored. To highlight general responses to defoliation vs. different locations, we analyzed the transcriptome of cv. Sangiovese berries sampled at four development stages from pre-flowering defoliated vines in two different geographical areas of Italy. We obtained and validated five markers of the early defoliation treatment in Sangiovese, an ATP-binding cassette transporter, an auxin response factor, a cinnamyl alcohol dehydrogenase, a flavonoid 3-O-glucosyltransferase and an indole-3-acetate beta-glucosyltransferase. Candidate molecular markers were also obtained in another three grapevine genotypes (Nero d'Avola, Ortrugo, and Ciliegiolo), subjected to the same level of selective pre-flowering defoliation (PFD) over two consecutive years in their different areas of cultivation. The flavonol synthase was identified as a marker in the pre-veraison phase, the jasmonate methyltransferase during the transition phase and the abscisic acid receptor PYL4 in the ripening phase. The characterization of transcriptome changes in Sangiovese berry after PFD highlights, on one hand, the stronger effect of environment than treatment on the whole berry transcriptome rearrangement during development and, on the other, expands existing knowledge of the main molecular and biochemical modifications occurring in defoliated vines. Moreover, the identification of candidate genes associated with PFD in different genotypes and environments provides new insights into the applicability and repeatability of this crop practice, as well as its possible agricultural and qualitative outcomes across genetic and environmental variability.

Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role in tumor heterogeneity

Abstract: The goal of this study was to understand if exosomes derived from high-metastatic cells may influence the behavior of less aggressive cancer cells and the properties of the endothelium. We found that metastatic colon cancer cells are able to transfer their amoeboid phenotype to isogenic primary cancer cells through exosomes, and that this morphological transition is associated with the acquisition of a more aggressive behavior. Moreover, exosomes from the metastatic line (SW620Exos) exhibited higher ability to cause endothelial hyperpermeability than exosomes from the non metastatic line (SW480Exos). SWATH-based quantitative proteomic analysis highlighted that SW620Exos are significantly enriched in cytoskeletal-associated proteins including proteins activating the RhoA/ROCK pathway, known to induce amoeboid properties and destabilization of endothelial junctions. In particular, thrombin was identified as a key mediator of the effects induced by SW620Exos in target cells, in which we also found a significant increase of RhoA activity. Overall, our results demonstrate that in a heterogeneous context exosomes released by aggressive sub-clones can contribute to accelerate tumor progression by spreading malignant properties that affect both the tumor cell plasticity and the endothelial cell behavior.

Microplastic Incorporation into Soil in Agroecosystems

Abstract: We live in a plastic age (Thompson et al., 2009), with microplastic (typically defined as plastic particles < 5mm) becoming an increasingly appreciated aspect of environmental pollution. Research has been overwhelmingly focused on aquatic systems, especially the oceans, but there is a current shift to more strongly consider terrestrial ecosystems (Rillig, 2012; Horton et al., 2017). In particular agroecosystems are coming into focus as a major entry point for microplastics in continental systems (Nizzetto et al., 2016b), where contamination might occur via different sources as sludge amendment or plastic mulching (Steinmetz et al., 2016). Given the central role of agroecosystems, including their soil biodiversity (Rillig et al., 2016), in food production, such numbers are potential cause for concern. Field data on measured microplastic presence in agricultural soils are still not widely available, but nevertheless this material is certain to arrive at the soil surface. The fate of material deposited at the soil surface is not clear: particles may be removed by wind or water erosion, becoming airborne, or may be lost by surface runoff (Nizzetto et al., 2016a). Nevertheless, a substantial part of the microplastic (or nanoplastic following further disintegration) is expected to enter the soil. The degree of hazard represented by microplastic to various soil biota is not clear. Direct evidence comes from experimental work on earthworms, on which microbeads had negative effects (Huerta Lwanga et al., 2016; also reviewed in Horton et al., 2017). Data on impacts on other soil biota groups are not available. However, Kiyama et al. (2012) have shown that polystyrene beads can be taken up by the nematode Caenorhabditis elegans; this means the material could also accumulate in the soil food web (Rillig, 2012). Movement into soil is an important aspect of assessing risk: will soil biota be exposed to microplastics? Here, we sketch what is known about movement of such particles in soil, which players and factors could influence this, and we chart avenues for research aimed at the movement and distribution of microplastic in agricultural soils.

Organic coating on biochar explains its nutrient retention and stimulation of soil fertility

Abstract: Amending soil with biochar (pyrolized biomass) is suggested as a globally applicable approach to address climate change and soil degradation by carbon sequestration, reducing soil-borne greenhouse-gas emissions and increasing soil nutrient retention. Biochar was shown to promote plant growth, especially when combined with nutrient-rich organic matter, e.g., co-composted biochar. Plant growth promotion was explained by slow release of nutrients, although a mechanistic understanding of nutrient storage in biochar is missing. Here we identify a complex, nutrient-rich organic coating on co-composted biochar that covers the outer and inner (pore) surfaces of biochar particles using high-resolution spectro(micro)scopy and mass spectrometry. Fast field cycling nuclear magnetic resonance, electrochemical analysis and gas adsorption demonstrated that this coating adds hydrophilicity, redox-active moieties, and additional mesoporosity, which strengthens biochar-water interactions and thus enhances nutrient retention. This implies that the functioning of biochar in soil is determined by the formation of an organic coating, rather than biochar surface oxidation, as previously suggested. Biochar promotes plant growth via a slow release of nutrients; however, a mechanistic understanding of nutrient storage in biochar is lacking. Here, using high-resolution spectromicroscopy and mass spectrometry, the authors identify an organic coating on co-composted particles that enhances nutrient retention.

Spatio-temporal dynamics of a planktonic system and chlorophyll distribution in a 2D spatial domain: matching model and data

Abstract: Field data on chlorophyll distribution are investigated in a two-dimensional spatial domain of the Mediterranean Sea by using for phytoplankton abundances an advection-diffusion-reaction model, which includes real values for physical and biological variables. The study exploits indeed hydrological and nutrients data acquired in situ, and includes intraspecific competition for limiting factors, i.e. light intensity and phosphate concentration. As a result, the model allows to analyze how both the velocity field of marine currents and the two components of turbulent diffusivity affect the spatial distributions of phytoplankton abundances in the Modified Atlantic Water, the upper layer of the water column of the Mediterranean Sea. Specifically, the spatio-temporal dynamics of four phytoplankton populations, responsible for about 80% of the total chlorophyll a, are reproduced. Results for phytoplankton abundances obtained by the model are converted in chlorophyll a concentrations and compared with field data collected in twelve marine sites along the Cape Passero (Sicily)- Misurata (Libya) transect. Statistical checks indicate a good agreement between theoretical and experimental distributions of chlorophyll concentration. The study can be extended to predict the spatio-temporal behaviour of the primary production, and to prevent the consequent decline of some fish species in the Mediterranean Sea.

Creating stable Floquet-Weyl semimetals by laser-driving of 3D Dirac materials.

Abstract: Tuning and stabilizing topological states, such as Weyl semimetals, Dirac semimetals or topological insulators, is emerging as one of the major topics in materials science. Periodic driving of many-body systems offers a platform to design Floquet states of matter with tunable electronic properties on ultrafast timescales. Here we show by first principles calculations how femtosecond laser pulses with circularly polarized light can be used to switch between Weyl semimetal, Dirac semimetal and topological insulator states in a prototypical three-dimensional (3D) Dirac material, Na3Bi. Our findings are general and apply to any 3D Dirac semimetal. We discuss the concept of time-dependent bands and steering of Floquet-Weyl points and demonstrate how light can enhance topological protection against lattice perturbations. This work has potential practical implications for the ultrafast switching of materials properties, such as optical band gaps or anomalous magnetoresistance.

Comparison of US Strain Elastography and Entero-MRI to Typify the Mesenteric and Bowel Wall Changes during Crohn's Disease: A Pilot Study.

Abstract: Purpose. To evaluate and compare the mesenteric and bowel wall changes during Crohn’s disease (CD) on ultrasonography (US) Strain Elastography (SE) and Enterography Magnetic Resonance Imaging (E-MRI). Methods. From July 2014 to September 2016, 35 patients with ileocolonoscopy diagnosis of CD were prospectively examined with E-MRI and in the same time with US and SE. Results. A total of 41 affected bowel segments and 35 unaffected bowel segments in 35 patients were evaluated. US-SE color-scale coding showed a blue color pattern in the fibrotic mesentery and bowel wall in 15 patients and a green color pattern in the edematous ones in 20 patients. The signal of the bowel wall and mesenteric fat was iso/hypointense on T2-weighted sequence in the fibrotic pattern (23/35 and 12/35 patients) and hyperintense in the edematous pattern (12/35 and 23/35 patients). Mean ADC values were, respectively, 2, ,33 × 10−3 for the fibrotic mesentery and 2, ,28 × 10−3 for edematous one. There was a statistical correlation between US-SE color-scale and T2 signal intensity and between the US-SE color-scale and ADC maps. Conclusions. US-SE, ADC, and signal intensity on T2-weighted sequences on MR prove to be useful tools for the evaluation of CD pattern.

A novel community driven software for functional enrichment analysis of extracellular vesicles data

Abstract: Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group However, such software tools may fail to capture “what the community needs in a tool” Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

Abstract: In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

Pneumococcal Colonization in the Familial Context and Implications for Anti-Pneumococcal Immunization in Adults: Results from the BINOCOLO Project in Sicily

Abstract: The spread of Streptococcus pneumoniae within families has been scarcely investigated so far. This feasibility study aimed to estimate the prevalence of pneumococcal carriage in school-aged children and co-habiting relatives and to explore the potential link between the family environment and the sharing of pneumococcal serotypes covered by the vaccine. Oropharyngeal samples of 146 subjects belonging to 36 different family groups were molecularly tested for pneumococcal detection and serotyping. The overall prevalence of pneumococcal carriage was 65.8% (n = 96/146), whereas it was higher among schoolchildren (77.8%, n = 28/36); subjects of seven years of age had the highest odds of being colonized (odds ratio, OR = 5.176; p = 0.145). Pneumococcal serotypes included in the 13-valent conjugate vaccine formulation were largely detected in the study population and multiple serotypes colonization was considerable. Factors relating to a close proximity among people at the family level were statistically associated with pneumococcal carriage (OR = 2.121; p = 0.049), as well as active smoking habit with a clear dose-response effect (ORs = 1.017-3.326). About half of family clusters evidenced similar patterns of carried pneumococcal serotypes and the odds of sustaining a high level of intrafamilial sharing increased with household size (ORs = 1.083-5.000). This study highlighted the potential role played by the family environment in sustaining both the circulation and horizontal transmission of pneumococcus.

Poly(N-isopropylacrylamide) and Copolymers: A Review on Recent Progresses in Biomedical Applications

Abstract: The innate ability of poly(N-isopropylacrylamide) (PNIPAAm) thermo-responsive hydrogel to copolymerize and to graft synthetic polymers and biomolecules, in conjunction with the highly controlled methods of radical polymerization which are now available, have expedited the widespread number of papers published in the last decade-especially in the biomedical field. Therefore, PNIPAAm-based hydrogels are extensively investigated for applications on the controlled delivery of active molecules, in self-healing materials, tissue engineering, regenerative medicine, or in the smart encapsulation of cells. The most promising polymers for biodegradability enhancement of PNIPAAm hydrogels are probably poly(ethylene glycol) (PEG) and/or poly(e-caprolactone) (PCL), whereas the biocompatibility is mostly achieved with biopolymers. Ultimately, advances in three-dimensional bioprinting technology would contribute to the design of new devices and medical tools with thermal stimuli response needs, fabricated with PNIPAAm hydrogels.

Effect of Morphology and Size of Halloysite Nanotubes on Functional Pectin Bionanocomposites for Food Packaging Applications.

Abstract: Pectin bionanocomposite films filled with various concentrations of two different types of halloysite nanotubes were prepared and characterized in this study as potential films for food packaging applications. The two types of halloysite nanotubes were long and thin (patch) (200–30 000 nm length) and short and stubby (Matauri Bay) (50–3000 nm length) with different morphological, physical, and dispersibility properties. Both matrix (pectin) and reinforcer (halloysite nanotubes) used in this study are considered as biocompatible, natural, and low-cost materials. Various characterization tests including Fourier transform infrared spectroscopy, field emission scanning electron microscopy, release kinetics, contact angle, and dynamic mechanical analysis were performed to evaluate the performance of the pectin films. Exceptional thermal, tensile, and contact angle properties have been achieved for films reinforced by patch halloysite nanotubes due to the patchy and lengthy nature of these tubes, which form a b...

Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo Chronic Myelogenous Leukemia cell growth.

Abstract: Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in vitro and in vivo cancer cell growth.

Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial.

Abstract: Objectives:The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity.Methods:Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk–based infant formula (co

Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis

Abstract: Background Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS. Methods Ileal biopsies were obtained from 50 HLA-B27 + patients with AS and 20 normal subjects. Silver stain was used to visualise bacteria. Ileal expression of tight and adherens junction proteins was investigated by TaqMan real-time (RT)-PCR and immunohistochemistry. Serum levels of lipopolysaccharide (LPS), LPS-binding protein (LPS-BP), intestinal fatty acid-BP (iFABP) and zonulin were assayed by ELISA. Monocyte immunological functions were studied in in vitro experiments. In addition the effects of antibiotics on tight junctions in human leukocyte antigen (HLA)-B27 transgenic (TG) rats were assessed. Results Adherent and invasive bacteria were observed in the gut of patients with AS with the bacterial scores significantly correlated with gut inflammation. Impairment of the gut vascular barrier (GVB) was also present in AS, accompanied by significant upregulation of zonulin, and associated with high serum levels of LPS, LPS-BP, iFABP and zonulin. In in vitro studies zonulin altered endothelial tight junctions while its epithelial release was modulated by isolated AS ileal bacteria. AS circulating monocytes displayed an anergic phenotype partially restored by ex vivo stimulation with LPS+sCD14 and their stimulation with recombinant zonulin induced a clear M2 phenotype. Antibiotics restored tight junction function in HLA-B27 TG rats. Conclusions Bacterial ileitis, increased zonulin expression and damaged intestinal mucosal barrier and GVB, characterises the gut of patients with AS and are associated with increased blood levels of zonulin, and bacterial products. Bacterial products and zonulin influence monocyte behaviour.

Blocking CGRP in migraine patients – a review of pros and cons

Abstract: Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks Here, we review the pros and cons of blocking CGRP in migraine patients To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor Several trials have been conducted to test the efficacy and safety of these drugs In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies In addition, the efficacy is in line with other currently used prophylactic treatments The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases In addition, long-term effects are still unknown Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing However, these effects have so far not been reported in human studies In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceed the cons

Cardiovascular Disease in Ageing: An Overview on Thoracic Aortic Aneurysm as an Emerging Inflammatory Disease.

Abstract: Medial degeneration associated with thoracic aortic aneurysm and acute aortic dissection was originally described by Erdheim as a noninflammatory lesion related to the loss of smooth muscle cells and elastic fibre fragmentation in the media. Recent evidences propose the strong role of a chronic immune/inflammatory process in aneurysm evocation and progression. The coexistence of inflammatory cells with markers of apoptotic vascular cell death in the media of ascending aorta with aneurysms and type A dissections raises the possibility that activated T cells and macrophages may contribute to the elimination of smooth muscle cells and degradation of the matrix. On the other hand, several inflammatory pathways (including TGF-β, TLR-4 interferon-γ, chemokines, and interferon-γ) seem to be involved in the medial degeneration related to aged and dilated aorta. This is an overview on thoracic aortic aneurysm as an emerging inflammatory disease.

Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

Abstract: 1.1. Cardiovascular disease and dyslipidemia: prevalence and global economic impact Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, reaching 31% of deaths in 2012 [1]. In particular, atherosclerosis and ischemic heart disease (IHD) are the main causes of premature death in Europe and are responsible for 42% of deaths in women and 38% in men under 75 years old [2]. The global economic impact of CVD is estimated to have been US $906 billion in 2015 and is expected to rise by 22% by 2030 [3]. Cardiovascular diseases also represent the major cause of disability in developed countries. It has been estimated that their growing burden could lead to a global increase in loss of disability-adjusted life years (DALYs), from a loss of 85 million DALYs in 1990 to a loss of ~150 million DALYs in 2020, becoming a major non-psychological cause of lost productivity [4]. Several risk factors contribute to the etiology and development of CVD; they are divided into those modifiable through lifestyle changes or by taking a pharmacologic treatment (e.g. for hypertension, smoking, diabetes mellitus, hypercholesterolemia) and those that are not modifiable (age, male gender, and family history) [5]. Elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) blood concentrations are the major modifiable risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) in certain conditions are considered protective [6]. Moreover, LDL-C remains a fundamental CV risk factor (and a main target of therapy) even when statins are largely used in the general population [7]. An examination of the data of 18 053 participants aged ≥ 20 years who participated in the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2006 showed that the unadjusted prevalence of hypercholesterolemia ranged from 53.2% to 56.1% in United States adults [8]. Differences related to gender and race or ethnicity were observed; in particular, a lower rate of control was found among women than men and lower rates of having a cholesterol check and being told about hypercholesterolemia were reported by African Americans and Mexican Americans than whites [8]. A recent report from the American Heart Association confirmed that in the US only 75.7% of children and 46.6% of adults present targeted TC levels (TC < 170 mg/dl for children and < 200 mg/dl for adults, in untreated individuals) [9]. The pattern is similar in other Western countries [10, 11].