Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

EBV (Epstein-Barr Virus) and other human DNA viruses are associated with autoimmune syndromes in epidemiologic studies. In this work, immunoglobulin G response to EBV-encoded proteins which share regions with human immune response proteins from the human host including ZEBRA (BZLF-1 encoded protein), BALF-2 recombinase expressed primarily during the viral lytic replication cycle, and EBNA-1 (Epstein-Barr Virus Nuclear Antigen) expressed during the viral latency cycle respectively were characterized using a laser-printed micro-array ( PEPperprint.com ). IgG response to conserved "A/T hooks" in EBV-encoded proteins such as EBNA-1 and the BALF-2 recombinase related to host DNA-binding proteins including RAG-1 recombinase and histones, and EBV-encoded virokines such as the IL-10 homologue BCRF-1 suggest further directions for clinical research. The author suggests that proteomic "molecular fingerprints" of the immune response to viral proteins shared with human immune response genes are potentially useful in early diagnosis and monitoring of autoantibody production and response to therapy in EBV-related autoimmune syndromes

Innate immune modulation induced by EBV lytic infection promotes endothelial cell inflammation and vascular injury in scleroderma

Microvascular injury is considered an initial event in the pathogenesis of scleroderma and endothelial cells are suspected of being the target of the autoimmune process seen in the disease. EBV has long been proposed as a trigger for autoimmune diseases, including scleroderma. Nevertheless, its contribution to the pathogenic process remains poorly understood. In this study, we report that EBV lytic antigens are detected in scleroderma dermal vessels, suggesting that endothelial cells might represent a target for EBV infection in scleroderma skin. We show that EBV DNA load is remarkably increased in peripheral blood, plasma and circulating monocytes from scleroderma patients compared to healthy EBV carriers, and that monocytes represent the prominent subsets of EBV-infected cells in scleroderma. Given that monocytes have the capacity to adhere to the endothelium, we then investigated whether monocyte-associated EBV could infect primary human endothelial cells. We demonstrated that endothelial cells are infectable by EBV, using human monocytes bound to recombinant EBV as a shuttle, even though cell-free virus failed to infect them. We show that EBV induces activation of TLR9 innate immune response and markers of vascular injury in infected endothelial cells and that up-regulation is associated with the expression of EBV lytic genes in infected cells. EBV innate immune modulation suggests a novel mechanism mediating inflammation, by which EBV triggers endothelial cell and vascular injury in scleroderma. In addition, our data point to up-regulation of EBV DNA loads as potential biomarker in developing vasculopathy in scleroderma. These findings provide the framework for the development of novel therapeutic interventions to shift the scleroderma treatment paradigm towards antiviral therapies

Harmony of transitions in assessing interpersonal motivations in transcripts analysis can discriminate between Adult Attachment Interview secure and disorganized individuals

SUMMARY. Aim. Assessing Interpersonal Motivations in Transcripts (AIMIT) is a validated coding system to assess the activation of interpersonal motivational systems (IMS) in the transcripts of psychotherapy sessions. The Transition Index (TI) is an AIMIT measure that reflects the levels of organisation, synchronisation and harmony amongst two or more IMS when they are rapidly shifting or simultaneously in the clinical dialogue. It is supposed to be a measure of integration and coherence of the patient’s state of mind within the psychotherapeutic sessions. It has also been hypothesized that low TI could be a marker for disorganization of attachment of the patient leading to difficulties in the therapeutic relationships and ruptures in the therapeutic alliance. In order to assess this hypothesis we tested its capability to discriminate between Adult Attachment Interview (AAI) organized and disorganized individuals. Methods. Two groups of 15 transcriptions of AAI matched for age and sex, one classified as free-autonomous and one as disorganized, were analysed by the AIMIT method. Results. Compared to organized individuals, disorganized patients at AAI reported lower TI scores (3.7±0.63 vs 3.0±0.53; F=2.98, p=0.005). Furthermore, TI showed a good discriminant capability (Wilks’ Lambda=0.77, p=0.004). Discussion and Conclusion. This result seems to confirm the usefulness and reliability of AIMIT analysis in evaluating the interpersonal difficulties which often characterize the therapeutic relationship with disorganized attachment patient

Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury

Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment.Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects.The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc

Set up and preliminary validation of a small spatial sound reproduction system for clinical purposes

Hearing research and audio technology have met to cope with hearing impairment issues under multiple aspects. Among them, spatial sound reproduction systems have been used for both clinical and research purposes to optimize signal processing algorithms of Hearing Aids (HAs) and for the assessment of hearing loss under complex acoustic conditions. Furthermore, spatial sound reproduction systems are also well suited for the administration of listening tests properly designed to optimize HAs fittings, for which ecological validity is crucial to achieve effective hearing improvement in daily life. Based on well-grounded 3D sound systems, this work discusses the procedure of installation, signal network set-up and evaluation of a Virtual Sound Environment (VSE) reproduction system that is meant to be replicated and used indoors in small settings for clinical purposes. The system, aimed at reproducing sound fields starting from 3rd-order ambisonics encodings, is based on a spherical array of 16 commercial 2-way active loudspeakers installed inside of a small acoustically dampened room of 35.5 m3. Results of this work can be summarized as follows: (i) a small spatial sound reproduction system was tuned and (ii) a preliminary investigation of the accuracy of the reproduced VSEs compared to the real environments was performed

Health Technological Supports to Detect Medication Errors: The Saniarp Case-Study

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Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three-Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal tablets were designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity. Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug release from tablets appeared to be sufficient to induce cell death as confirmed by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of treatment, when about 90% of the drug had been discharged from the tablets into the culture environment, 5-FU caused loss of cell-cell communications and apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral outgrowths and the death of all the cells was observed. Buccal matrix tablets could be considered a promising new approach to the locoregional treatment of OSCC. Risks of systemic toxicity are avoided since very low drug doses are delivered

EChO payload electronics architecture and SW design

EChO is a three-modules (VNIR, SWIR, MWIR), highly integrated spectrometer, covering the wavelength range from 0.55 μ m to 11.0 μ m. The baseline design includes the goal wavelength extension to 0.4 μ m while an optional LWIR module extends the range to the goal wavelength of 16.0 μ m. An Instrument Control Unit (ICU) is foreseen as the main electronic subsystem interfacing the spacecraft and collecting data from all the payload spectrometers modules. ICU is in charge of two main tasks: the overall payload control ( Instrument Control Function) and the housekeepings and scientific data digital processing ( Data Processing Function), including the lossless compression prior to store the science data to the Solid State Mass Memory of the Spacecraft. These two main tasks are accomplished thanks to the Payload On Board Software (P-OBSW) running on the ICU CPUs. <P /

Fresolimumab Treatment Decreases Biomarkers and Improves Clinical Symptoms in Systemic Sclerosis Patients

BACKGROUND. TGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TGF-β–regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients. METHODS. Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β–regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS). RESULTS. In patient skin, THBS1 expression rapidly declined after fresolimumab treatment in both groups (P = 0.0313 at 7 weeks and P = 0.0156 at 3 weeks), and skin expression of COMP exhibited a strong downward trend in both groups. Clinical skin disease dramatically and rapidly decreased (P \u3c 0.001 at all time points). Expression levels of other TGF-β–regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067). Dermal myofibroblast infiltration also declined in patient skin after fresolimumab (P \u3c 0.05). Baseline levels of THBS1 were predictive of reduced THBS1 expression and improved MRSS after fresolimumab treatment. CONCLUSION. The rapid inhibition of TGF-β–regulated gene expression in response to fresolimumab strongly implicates TGF-β in the pathogenesis of fibrosis in SSc. Parallel improvement in the MRSS indicates that fresolimumab rapidly reverses markers of skin fibrosis

The visible and near infrared module of EChO

The Visible and Near Infrared (VNIR) is one of the modules of EChO, the Exoplanets Characterization Observatory proposed to ESA for an M-class mission. EChO is aimed to observe planets while transiting by their suns. Then the instrument had to be designed to assure a high efficiency over the whole spectral range. In fact, it has to be able to observe stars with an apparent magnitude Mv = 9-12 and to see contrasts of the order of 10-4-10-5 necessary to reveal the characteristics of the atmospheres of the exoplanets under investigation. VNIR is a spectrometer in a cross-dispersed configuration, covering the 0.4-2.5 μm spectral range with a resolving power of about 330 and a field of view of 2 arcsec. It is functionally split into two channels respectively working in the 0.4-1.0 μm and 1.0-2.5 μm spectral ranges. Such a solution is imposed by the fact the light at short wavelengths has to be shared with the EChO Fine Guiding System (FGS) devoted to the pointing of the stars under observation. The spectrometer makes use of a HgCdTe detector of 512 by 512 pixels, 18 μm pitch and working at a temperature of 45 K as the entire VNIR optical bench. The instrument has been interfaced to the telescope optics by two optical fibers, one per channel, to assure an easier coupling and an easier colocation of the instrument inside the EChO optical bench. <P /