Expectations, Network Effects and Timing of Technology Adoption: Some Empirical Evidence from a Sample of SMEs in Italy

We provide evidence on the influence of expectations and network effects on the timing of technological adoption. By considering a sample of SMEs operating in Italy we focus on the determinants of their decision to adopt Fast Ethernet, a communication standard for Local Area Networks (LANs). We find that both expectations and network effects significantly affect the timing of adoption. In particular, price expectations generally tend to delay adoption and (indirect) network effects in the form of backward compatibility as well as informational spillovers tend to foster adoption. Firm size also matters.diffusion, network effects, expectations, LAN equipment, SMEs

Oestrogen replacement therapy reduces total plasma homocysteine and enhances genomic DNA methylation in postmenopausal women

Although oestrogen replacement therapy (ERT), which can affect the risk of major cancers, has been known to reduce total plasma homocysteine concentrations in postmenopausal women, the mechanisms and subsequent molecular changes have not yet been defined. To investigate the effect of ERT on homocysteine metabolism, thirteen healthy postmenopausal women were enrolled in a double-blind, placebo-controlled, randomized, cross-over study consisting of two 8-week long phases, placebo and conjugated equine oestrogen (CEE; 0·625 mg/d). Concentrations of total plasma homocysteine, vitamin B6and serum folate and vitamin B12were measured by conventional methods. Genomic DNA methylation was measured by a new liquid chromatography/MS method and promoter methylation status of the oestrogen receptor (ER)α,ERβandp16genes was analysed by methylation-specific PCR after bisulfite treatment. The CEE phase demonstrated a significantly decreased mean of total plasma homocysteine concentrations compared with the placebo phase (8·08 μmol/l (6·82–9·39)v.9·29 (7·53–11·35),P < 0·05) but there was no difference in the blood concentrations of the three B vitamins. The CEE phase also showed a significantly increased genomic DNA methylation in peripheral mononuclear cells compared with the placebo phase (2·85 (SD0·12) ng methylcytosine/μg DNAv.2·40 ± (SD0·15)P < 0·05). However, there was no difference in promoter methylation in theERα,ERβandp16genes. This study demonstrates that decreased homocysteinaemia by CEE therapy parallels with increased genomic DNA methylation, suggesting a potential new candidate mechanism by which ERT affects the risk of cancers and a possible new candidate biomarker for the oestrogen-related carcinogenesis through folate-related one-carbon metabolism

Gene expression profiling in circulating endothelial cells from systemic sclerosis patients shows an altered control of apoptosis and angiogenesis that is modified by iloprost infusion

ABSTRACT: INTRODUCTION: Circulating endothelial cells are increased in patients affected by Systemic Sclerosis and their number strongly correlates with vascular damage. The effects of Iloprost in Systemic sclerosis are only partially known. We aimed at studying the gene expression profile of circulating endothelial cells and the effects of Iloprost infusion on endothelial cells number and gene expression in patients with Systemic Sclerosis. METHODS: We enrolled 50 patients affected by Systemic Sclerosis: 37 patients without and 13 patients with digital ulcers. Blood samples were collected from all patients before and 72 hours after either a single day or five days eight hours Iloprost infusion. Blood samples were also collected from 50 sex and age matched healthy controls. Circulating endothelial cells and endothelial progenitors cells were detected in the peripheral blood of patients with Systemic Sclerosis by flow cytometry with a four-colour panel of antibodies. Statistical analysis was performed with the SPSS 16 statistical package. Circulating endothelial cells were then isolated from peripheral blood by immunomagnetic CD45 negative selection for the gene array study. RESULTS: The number of both circulating endothelial cells and progenitors was significantly higher in patients affected by Systemic Sclerosis than in controls and among patients in those with digital ulcers than in patients without them. Circulating endothelial cells and progenitors number increased after Iloprost infusion. Gene array analysis of endothelial cells showed a different transcriptional profile in patients compared to controls: indeed patients displayed an altered expression of genes involved in the control of apoptosis and angiogenesis. Iloprost infusion had a profound impact on endothelial cells gene expression since the treatment was able to modulate a very high number of transcripts. CONCLUSIONS: We report here that circulating endothelial cells in patients with Systemic Sclerosis show an altered expression of genes involved in the control of apoptosis and angiogenesis. Moreover we describe that Iloprost infusion has a strong effect on endothelial cells and progenitors since it is able to modulate both their number and their gene expression profile

High resolution preparation of monocyte-derived macrophages (MDM) protein fractions for clinical proteomics

<p>Abstract</p> <p>Background</p> <p>Macrophages are involved in a number of key physiological processes and complex responses such as inflammatory, immunological, infectious diseases and iron homeostasis. These cells are specialised for iron storage and recycling from senescent erythrocytes so they play a central role in the fine tuning of iron balancing and distribution. The comprehension of the many physiological responses of macrophages implies the study of the related molecular events. To this regard, proteomic analysis, is one of the most powerful tools for the elucidation of the molecular mechanisms, in terms of changes in protein expression levels.</p> <p>Results</p> <p>Our aim was to optimize a protocol for protein fractionation and high resolution mapping using human macrophages for clinical studies. We exploited a fractionation protocol based on the neutral detergent Triton X-114. The 2D maps of the fractions obtained showed high resolution and a good level of purity. Western immunoblotting and mass spectrometry (MS/MS analysis) indicated no fraction cross contamination. On 2D-PAGE mini gels (7 × 8 cm) we could count more than five hundred protein spots, substantially increasing the resolution and the number of detectable proteins for the macrophage proteome. The fractions were also evaluated, with preliminary experiments, using Surface Enhanced Laser Desorption Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS).</p> <p>Conclusion</p> <p>This relatively simple method allows deep investigation into macrophages proteomics producing discrete and accurate protein fractions, especially membrane-associated and integral proteins. The adapted protocol seems highly suitable for further studies of clinical proteomics, especially for the elucidation of the molecular mechanisms controlling iron homeostasis in normal and disease conditions.</p

Relationship Between Human Leucocyte Antigen Class I and Class II and Chronic Idiopathic Urticaria Associated With Aspirin and/or NSAIDs Hypersensitivity

Background. HLA genes play a role in the predisposition of several diseases. The aim was to analyze the prevalence of HLA class I phenotypes and HLA-DRB1* genotype in patients with CIU associated with ASA and NSAIDs hypersensitivity (AICU). Methods. 69 patients with AICU, and 200 healthy subjects. Results. Subjects with HLA-B44 and HLA-Cw5 antigens were more represented in patients with AICU than in control group. Subjects with HLA-A11, HLA-B13, HLACw4, and HLA-Cw7 antigen were more represented in control group than in patients with AICU. Multiple logistic regression demonstrated an association of HLA-Cw4 and HLA-Cw7 with a lower risk of AICU, whereas carriers of HLA-B44 phenotype had a higher risk of AICU. No differences were found between patients and controls as regards to HLA-DRB1* genotype. Conclusions. We observed an association between some HLA class-I antigens and AICU. To the best of our knowledge this is the first description of such association

In Celiac Disease, a Subset of Autoantibodies against Transglutaminase Binds Toll-Like Receptor 4 and Induces Activation of Monocytes

BACKGROUND: Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are a typical serological marker in patients with active disease, and may disappear during a gluten-free diet treatment. Involvement of infectious agents and innate immunity has been suggested but never proven. Molecular mimicry is one of the mechanisms that links infection and autoimmunity. METHODS AND FINDINGS: In our attempt to clarify the pathogenesis of celiac disease, we screened a random peptide library with pooled sera of patients affected by active disease after a pre-screening with the sera of the same patients on a gluten-free diet. We identified a peptide recognized by serum immunoglobulins of patients with active disease, but not by those of patients on a gluten-free diet. This peptide shares homology with the rotavirus major neutralizing protein VP-7 and with the self-antigens tissue transglutaminase, human heat shock protein 60, desmoglein 1, and Toll-like receptor 4. We show that antibodies against the peptide affinity-purified from the sera of patients with active disease recognize the viral product and self-antigens in ELISA and Western blot. These antibodies were able to induce increased epithelial cell permeability evaluated by transepithelial flux of [(3)H] mannitol in the T84 human intestinal epithelial cell line. Finally, the purified antibodies induced monocyte activation upon binding Toll-like receptor 4, evaluated both by surface expression of activation markers and by production of pro-inflammatory cytokines. CONCLUSIONS: Our findings show that in active celiac disease, a subset of anti-transglutaminase IgA antibodies recognize the viral protein VP-7, suggesting a possible involvement of rotavirus infection in the pathogenesis of the disease, through a mechanism of molecular mimicry. Moreover, such antibodies recognize self-antigens and are functionally active, able to increase intestinal permeability and induce monocyte activation. We therefore provide evidence for the involvement of innate immunity in the pathogenesis of celiac disease through a previously unknown mechanism of engagement of Toll-like receptor 4

Type 1 neurofibromatosis complicated by pulmonary artery hypertension : a case report

We describe the case of a patient with neurofibromatosis type 1 (NF1) complicated by severe pulmonary aterial hypertension (PAH) ; only seven cases have been reported on this association so far, and PAH seems to be related to the vascular involvement of neurofibromatosis. The histology of our patient’s lung tissue showed thickening of arteries and veins by medial and/or intimal hypertrophy and fibrosis. In order to exclude a familiar PAH, the analysis of the bone morphogenetic protein receptor 2 gene was carried out, but no mutations were found. On the basis of histological findings and of the results of genetic study we believe that PAH was a complication of NF1 in our patient and we suggest to screen patients with NF1 for the presence of PAH by means of trans-thoracic echocardiogram

Serum levels of soluble CD30 in adult patients affected by atopic dermatitis and its relation to age, duration of disease and Scoring Atopic Dermatitis index.

The value of CD30 and the soluble circulating fragment of CD30 (sCD30) for atopic dermatitis (AD) remains unclear. In particular, little is known about the effects of age, duration of disease and Scoring Atopic Dermatitis index (SCORAD) on the levels of serum sCD30 in patients affected by AD. In the present study, we have analysed serum sCD30 levels of adult patients affected by AD. The study's population includes 18 non-smoking outpatients, with a diagnosis of AD. As a control group we studied 18 non-atopic subjects from laboratory staff, matched for sex and age. These subjects had no history of AD, urticaria or seasonal or perennial rhinitis or asthma, and had negative skin prick test to a panel of allergens. The sCD30 serum levels were clearly higher in patients affected by AD (14.2+/-9.0 IU/ml) than in healthy subjects (1.2+/-0.8 IU/ml) (p<0.001). No differences were observed between males and females affected by atopic dermatitis, regarding age, duration of disease and SCORAD. Significant correlations were found between serum levels of sCD30 levels and age (r=-0.55; 95% confidence interval (CI) for r (Fisher's z transformed)=-0.81 to -0.12; p=0.01), duration of the disease (months) (r=-0.64; 95% CI for r (Fisher's z transformed)=-0.85 to -0.24; p=0.004) and SCORAD (r=-0.74; 95% CI for r (Fisher's z transformed)=-0.89 to -0.42; p=0.004). As demonstrated by the close correlation with age, duration of disease and SCORAD, serum levels of sCD30 appear to be an additional marker for the follow-up of AD

Low Levels of Serum Paraoxonase Activities are Characteristic of Metabolic Syndrome and May Influence the Metabolic-Syndrome-Related Risk of Coronary Artery Disease

Low concentrations of plasma high-density lipoprotein (HDLs) are characteristic in metabolic syndrome (MS). The antioxidant ability of HDLs is, at least in part, attributable to pleiotropic serum paraoxonase (PON1). Different PON1 activities have been assessed in 293 subjects with (n = 88) or without MS (n = 205) and with (n = 195) or without (n = 98) angiographically proven coronary artery disease (CAD). MS subjects had low PON1 activities, with a progressively decreasing trend by increasing the number of MS abnormalities. The activity versus 7-O-diethyl phosphoryl,3-cyano,4-methyl,7-hydroxycoumarin (DEPCyMC), which is considered a surrogate marker of PON1 concentration, showed the most significant association with MS, independently of both HDL and apolipoprotein A-I levels. Subjects with MS and low DEPCyMCase activity had the highest CAD risk (OR 4.34 with 95% CI 1.44–13.10), while no significant increase of risk was found among those with MS but high DEPCyMCase activity (OR 1.45 with 95% CI 0.47–4.46). Our results suggest that low PON1 concentrations are typical in MS and may modulate the MS-related risk of CAD

Hyperhomocysteinemia and Mortality after Coronary Artery Bypass Grafting

BACKGROUND: The independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy) levels were measured in all participants, and a post-methionine loading (PML) test was performed in 77.7% of them (n = 272). After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90(th) percentile (25.2 µmol/L) of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively). The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses), high-sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic (MTHFR 677C→T polymorphism) and non-genetic (B-group vitamin status and renal function) tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001). CONCLUSIONS: HHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers