Effects of secukinumab on serum adipocytokines: preliminary data

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA. The aim of this study was to evaluate the possible interferences of secukinumab on different adipocytokines. We enrolled 28 patients with PsA, classified with the CASPAR criteria. Serum samples were stored at baseline and then at the first, the third and the sixth month of therapy. Resistin, chemerin, adiponectin and C-reactive protein (CRP) were dosed. When tested globally, none of the adipokine tested showed any statistically significant variation. However, when the male group was tested, both resistin and chemerin at M6 showed a significant decrease from baseline. CRP did not show any variation at any time point. Our study demonstrated that treatment with secukinumab has little influence on the levels of adipokines tested within the first six months of treatment even though it might exert different influence between males and females from a metabolic perspective. Further studies with greater numbers of patients are needed to determine whether these preliminary results have clinical relevance

Antiretroviral therapy in HIV/HCV co-infection Italian consensus workshop

About 50% of people living with the HIV infection in Italy are co-infected with HCV. In this group of patients, the primary cause of mortality is liver disease, which accounts for up to 14% of deaths. HIV/HCV co-infection also exposes patients to a higher risk of progression to AIDS, a faster evolution towards cirrhosis, more frequent drug toxicity, and lower tolerance for antiretroviral therapy. Moreover, HCV infection can play a part in increasing immune system depression; neurological, cognitive and renal damage; and bone fragility. Hence an optimal antiretroviral regimen needs to be chosen for co-administration with anti-HCV therapy and timed appropriately to improve the prognosis of co-infected HIV/HCV patients. Unfortunately, however, data on the safety and efficacy of antiretroviral drugs in these patients is scarce, as are studies of pharmacokinetics in patients with advanced liver impairment. Furthermore, restoring adequate immune constitution seems not to slow the progression of liver disease, and the metabolic and hepatic toxicity of some antiretroviral drugs can even contribute to inflammatory and fibrogenic processes. It is therefore essential that HIV/HCV co-infected patients receive only medications capable of ensuring the best immune recovery but possessing the lowest potential to trigger immune reconstitution syndrome or hepatic and metabolic damage

Towards a Comprehensive Asset Integrity Management (AIM) Approach for European Infrastructures

Abstract Transport infrastructure is the backbone of national economies, providing connections for people and goods, access to jobs and services, and enabling trade and economic growth. It is of paramount importance to preserve, maintain and upgrade the infrastructure network so that to sustain the economic growth and an intelligent mobility. Asset Integrity Management (AIM) approaches will therefore represent key tools for facing the infrastructure maintenance issue and for tackling the ageing that characterize already existing assets. This paper, starting from analyzing the current state of the art solutions in assets management (Enevoldsen, I., 2008), proposes a comprehensive AIM approach that aims at replacing current time-based approaches with a performance-based approach that can systematically take into account the dynamic nature of the transport network. This means moving from a deterministic to a probabilistic approach in design, rehabilitation and retrofitting of infrastructures for increasing life-time and reducing maintenance costs. Such approach therefore laid the basis of secure sustainable impact since by improving awareness and reducing uncertainties, it might allow achieving an optimal balance among available resources and planning of investments

OPTIMIZING RF LINACS AS DRIVERS FOR INVERSE COMPTON SOURCES: THE ELI-NP CASE

The design guide-lines of RF Linacs to fulfil the requirements of high spectral density Inverse Compton Sources for the photo-nuclear science are mostly taken from the expertise coming from high brightness electron Linacs driving X-ray FEL's. The main difference is the quest for maximum phase space density (instead of peak brightness), but many common issues and techniques are exploited, in order to achieve an optimum design and layout for the machine. A relevant example in this field is the design of the hybrid C-band multi-bunch RF Linacs for the ELI-NP Gamma Beam System, aiming at improving by two orders of magnitude the present state of the art in spectral density available for the gamma-ray beam produced

The future search for low-frequency axions and new physics with the FLASH resonant cavity experiment at Frascati National Laboratories

We present a proposal for a new experiment, the FINUDA magnet for Light Axion SearcH (FLASH), a large resonant-cavity haloscope in a high static magnetic field which is planned to probe new physics in the form of dark matter (DM) axions, scalar fields, chameleons, hidden photons, as well as high frequency gravitational waves (GWs). Concerning the QCD axion, FLASH will search for these particles as the DM in the mass range (0.49-1.49) ueV, thus filling the mass gap between the ranges covered by other planned searches. A dedicated Microstrip SQUID operating at ultra-cryogenic temperatures will amplify the signal. The frequency range accessible overlaps with the Very High Frequency (VHF) range of the radio wave spectrum and allows for a search in GWs in the frequency range (100-300) MHz. The experiment will make use of the cryogenic plant and magnet of the FINUDA experiment at INFN Frascati National Laboratories near Rome (Italy); the operations needed to restore the functionalities of the apparatus are currently underway. We present the setup of the experiment and the sensitivity forecasts for the detection of axions, scalar fields, chameleons, hidden photons, and GWs

Physico-chemical properties and toxicological effects on plant and algal models of carbon nanosheets from a nettle fibre clone.

peer reviewedCarbon nanosheets are two-dimensional nanostructured materials that have applications as energy storage devices, electrochemical sensors, sample supports, filtration membranes, thanks to their high porosity and surface area. Here, for the first time, carbon nanosheets have been prepared from the stems and leaves of a nettle fibre clone, by using a cheap and straight-forward procedure that can be easily scaled up. The nanomaterial shows interesting physical parameters, namely interconnectivity of pores, graphitization, surface area and pore width. These characteristics are similar to those described for the nanomaterials obtained from other fibre crops. However, the advantage of nettle over other plants is its fast growth and easy propagation of homogeneous material using stem cuttings. This last aspect guarantees homogeneity of the starting raw material, a feature that is sought-after to get a nanomaterial with homogeneous and reproducible properties. To evaluate the potential toxic effects if released in the environment, an assessment of the impact on plant reproduction performance and microalgal growth has been carried out by using tobacco pollen cells and the green microalga Pseudokirchneriella subcapitata. No inhibitory effects on pollen germination are recorded, while algal growth inhibition is observed at higher concentrations of leaf carbon nanosheets with lower graphitization degree

Circulating sCD14 Is Associated with Virological Response to Pegylated-Interferon-Alpha/Ribavirin Treatment in HIV/HCV Co-Infected Patients

Microbial translocation (MT) through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10) reduction from baseline after 12 weeks of therapy) and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively), but similar T-cell activation compared to Non-EVR (Null Responders, NR) and Non-SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014).In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy

Activin A Induces Langerhans Cell Differentiation In Vitro and in Human Skin Explants

Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFβ. Ιn vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFβ. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFβ family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFβ. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFβ, responsible for LC differentiation during inflammatory/autoimmune conditions

The CC-NB-LRR-Type Rdg2a Resistance Gene Confers Immunity to the Seed-Borne Barley Leaf Stripe Pathogen in the Absence of Hypersensitive Cell Death

BACKGROUND: Leaf stripe disease on barley (Hordeum vulgare) is caused by the seed-transmitted hemi-biotrophic fungus Pyrenophora graminea. Race-specific resistance to leaf stripe is controlled by two known Rdg (Resistance to Drechslera graminea) genes: the H. spontaneum-derived Rdg1a and Rdg2a, identified in H. vulgare. The aim of the present work was to isolate the Rdg2a leaf stripe resistance gene, to characterize the Rdg2a locus organization and evolution and to elucidate the histological bases of Rdg2a-based leaf stripe resistance. PRINCIPLE FINDINGS: We describe here the positional cloning and functional characterization of the leaf stripe resistance gene Rdg2a. At the Rdg2a locus, three sequence-related coiled-coil, nucleotide-binding site, and leucine-rich repeat (CC-NB-LRR) encoding genes were identified. Sequence comparisons suggested that paralogs of this resistance locus evolved through recent gene duplication, and were subjected to frequent sequence exchange. Transformation of the leaf stripe susceptible cv. Golden Promise with two Rdg2a-candidates under the control of their native 5′ regulatory sequences identified a member of the CC-NB-LRR gene family that conferred resistance against the Dg2 leaf stripe isolate, against which the Rdg2a-gene is effective. Histological analysis demonstrated that Rdg2a-mediated leaf stripe resistance involves autofluorescing cells and prevents pathogen colonization in the embryos without any detectable hypersensitive cell death response, supporting a cell wall reinforcement-based resistance mechanism. CONCLUSIONS: This work reports about the cloning of a resistance gene effective against a seed borne disease. We observed that Rdg2a was subjected to diversifying selection which is consistent with a model in which the R gene co-evolves with a pathogen effector(s) gene. We propose that inducible responses giving rise to physical and chemical barriers to infection in the cell walls and intercellular spaces of the barley embryo tissues represent mechanisms by which the CC-NB-LRR-encoding Rdg2a gene mediates resistance to leaf stripe in the absence of hypersensitive cell death.Davide Bulgarelli, Chiara Biselli, Nicholas C. Collins, Gabriella Consonni, Antonio M. Stanca, Paul Schulze-Lefert and Giampiero Val

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection