Sensitivity and specificity of mastoid vibration test in detection of effects of vestibular neuritis [Sensibilità e specificità del test della vibrazione mastoidea nella individuazione degli esiti della neurite vestibolare]

Aim of this study was to determine sensitivity and specificity of the mastoid vibration test in patients who had suffered an attack of vestibular neuritis. Results were compared with the caloric test and two bedside tests of vestibular function (head shaking test and head thrust test). Results are reported in 28 patients who had a residual vestibular deficit 6 months after acute neuritis and in 25 healthy subjects. Mastoid vibration nystagmus was evoked in 21 patients but not in controls. In these patients, mastoid vibration test had a sensitivity of 75% and specificity of 100%. Since one patient had inverted mastoid vibration nystagmus, specificity of identification on the pathological side was 95%. Sensitivity of the test increased with increasing severity of the vestibular lesion. Indeed, mastoid vibration nystagmus was induced in 93% of patients with caloric paralysis and in 58% of those with caloric paresis. Nystagmus could usually be modulated or elicited by stimulation of either mastoid. In the few patients in whom mastoid vibration nystagmus was elicited only from one side, or when there was a clear difference in intensity of the nystagmus induced on the two sides, the stimulated side was more often the affected side. Four patients still showed spontaneous nystagmus. The caloric test was abnormal in 26/28 patients (93%) with paralysis in 16 and paresis in 12; 71% of patients had a head shaking induced nystagmus: 64% had an asymmetrical response in head thrust test. In conclusion, mastoid vibration test was overall more sensitive than head thrust test. Mastoid vibration test was slightly less sensitive than head shaking test in patients with severe residual deficit and more sensitive in patients with partial deficit. Mastoid vibration test, a valid, low cost clinical screening test for rapid detection of asymmetrical vestibular function, does not cause patient discomfort. It is suggested that this test be included in the diagnostic workup of all patients with suspected vestibular dysfunction

Patient Perceptions of Effectiveness in Treatments for Menière's Disease: a National Survey in Italy

Objective: The aim of this study was to investigate current treatment practices and self-reported effectiveness in Menière's disease. Materials and Methods: Members of two Italian Menière's disease support (n=170) with ≥6-month history of Menière's disease were administered an online survey about recent treatments. Vertigo episode count, work absenteeism, and limitations in family life, social life,work or travel, as included in the Social Life and Work Impact of Dizziness (SWID) Questionnaire before and after recent treatments were queried. Results: Twenty-four different treatments were reported for Menière's disease, with dietary modifications (55%), diuretics (47%), and betahistine (41%) being most common. The majority (71%) received multiple simultaneous treatments. Prior to the most recent treatments 78-89% of respondents indicated limitations in family or social life, work or traveling. After their most recent treatment, respondents reported improvements in mean vertigo episode counts (5.7±7.6 vs. 2.6 ±4.6, p<0.001), days off work per month (10.1 ±9.2 vs. 4.2 ±6.7, p<0.001), and proportions indicating limitations in any functional measure assessed (p<0.05). These findings were consistent regardless of treatment approach (all p<0.05). Intratympanic gentamicin provided the greatest reductions in vertigo count, functional limitations, and work absenteeism (all p<0.01) as well as the fewest respondents reporting post-treatment functional limitations (16-37%). Conclusions: Despite numerous treatment approaches targeting different proposed pathophysiology for Menière's disease in this cross-sectional survey, all treatments are reported as effective by patients. These findings support a prominent placebo effect in Menière's disease and highlight challenges in studying treatment outcomes; there is a critical need to better understand Menière's disease

Ehrlichia infection in Italy.

Immunoglobulin M seroconversion to Ehrlichia chaffeensis was documented in U.S. citizens bitten by ticks in Sardinia. Seven cases of suspected ehrlichiosis in local residents were not confirmed by laboratory tests. In Alpine areas antibodies to E. phagocytophila were detected in persons at high risk, i.e., foresters (8.6%) and hunters (5.5%), and in controls (1.5%). Of 153 persons bitten by ticks, only one was Ehrlichia antibody-positive after 6 months

A degrading Bouc\u2013Wen model for the hysteresis of reinforced concrete structural elements

This paper presents a smooth hysteresis model for reinforced concrete (RC) structural elements based on the differential equation of the Bouc?Wen model. Stiffness degradation and strength degradation are defined by introducing a damage index that includes both dissipated energy and maximum displacement. The pinching effect acts directly on the stiffness of the system and is controlled by an activation energy. The degrading functions are connected to the actual processes with which the damage occurs, thereby giving each parameter a physical meaning. The simple formulation of the model allows a straightforward identification of the best-fitting parameters and an easy interpretation of the results. Applications to the cyclic behaviour of RC structural elements demonstrate that the model is well capable of describing complex hysteretic behaviours involving degradation and pinching effects

Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

Background: The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic associations with cutaneous subtype and internal organ involvement have been also described. However, little is known about the potential of autoantibodies to exert a direct pathogenic role in SSc. The aim of the study is to assess the pathogenic capacity of anti-DNA-topoisomerase I (anti-Topo-I) and anti-centromeric protein B (anti-Cenp-B) autoantibodies to induce pro-fibrotic markers in dermal fibroblasts. Methods: Dermal fibroblasts were isolated from unaffected and affected skin samples of (n = 10) limited cutaneous SSc (LcSSc) patients, from affected skin samples of diffuse cutaneous (DcSSc) patients (n = 10) and from healthy subjects (n = 20). Fibroblasts were stimulated with anti-Topo-I, anti-Cenp-B IgGs, and control IgGs in ratios 1:100 and 1:200 for 24 h. Cells were also incubated with 10% SSc anti-Topo-I+ and anti-Cenp-B+ whole serum and with 10% control serum for 24 h. Viability was assessed by MTT test, while apoptosis was assessed by flow cytometry. Activation of pro-fibrotic genes ACTA2, COL1A1, and TAGLN was evaluated by quantitative real-time PCR (qPCR), while the respective protein levels alpha-smooth-muscle actin (\u3b1-SMA), type-I-collagen (Col-I), and transgelin (SM22) were assessed by immunocytochemistry (ICC). Results: MTT showed that anti-Cenp-B/anti-Topo-I IgGs and anti-Cenp-B+/anti-Topo-I+ sera reduced viability (in a dilution-dependent manner for IgGs) for all the fibroblast populations. Apoptosis is induced in unaffected LcSSc and control fibroblasts, while affected LcSSc/DcSSc fibroblasts showed apoptosis resistance. Basal mRNA (ACTA2, COL1A1, and TAGLN) and protein (\u3b1-SMA, Col-1, and SM22) levels were higher in affected LcSSc/DcSSc fibroblasts compared to LcSSc unaffected and to control ones. Stimulation with anti-Cenp-B/anti-Topo-I IgGs and with anti-Cenp-B+/anti-Topo-I+ sera showed a better induction in unaffected LcSSc and control fibroblasts. However, a statistically significant increase of all pro-fibrotic markers is reported also in affected LcSSc/DcSSc fibroblasts upon stimulation with both IgGs and sera. Conclusions: This study suggests a pathogenic role of SSc-specific autoantibodies to directly induce pro-fibrotic activation in human dermal fibroblasts. Therefore, besides the diagnostic and prognostic use of those autoantibodies, these data might further justify the importance of immunosuppressive drugs in the early stages of the autoimmune disease, including SSc

The metalloproteinase ADAM10 requires its activity to sustain surface expression

The metalloproteinase ADAM10 critically contributes to development, inflammation, and cancer and can be controlled by endogenous or synthetic inhibitors. Here, we demonstrate for the first time that loss of proteolytic activity of ADAM10 by either inhibition or loss of function mutations induces removal of the protease from the cell surface and the whole cell. This process is temperature dependent, restricted to mature ADAM10, and associated with an increased internalization, lysosomal degradation, and release of mature ADAM10 in extracellular vesicles. Recovery from this depletion requires de novo synthesis. Functionally, this is reflected by loss and recovery of ADAM10 substrate shedding. Finally, ADAM10 inhibition in mice reduces systemic ADAM10 levels in different tissues. Thus, ADAM10 activity is critically required for its surface expression in vitro and in vivo. These findings are crucial for development of therapeutic ADAM10 inhibition strategies and may showcase a novel, physiologically relevant mechanism of protease removal due to activity loss

AN IN VIVO MODEL OF HYPERACUTE REJECTION: CHARACTERIZATION AND EVALUATION OF THE EFFECT OF TRANSGENIC HUMAN COMPLEMENT INHIBITORS

Hyperacute rejection (HAR) occurring after transplantation within phylogenetically distant species is a severe reaction triggered by preexisting xenoreactive antibodies and complement activation, leading to the destruction of the donor organ. Expression of human complement inhibitors in transgenic pig organs prolongs the survival of xenograft in experimental models. Moreover, the extent of protection from hyperacute rejection is dependent on the level and site of expression of the transgenic molecules and, probably, on the combination of different molecules. In this regard a small animal model to test the efficacy of expression vectors and different human molecules could be very advantageous. A murine model developed in our laboratory was characterized by measurement of several parameters characteristic of HAR in the livers of control and transgenic mice expressing transgenic human DAF (CD55) or MCP (CD46) at the end of 2 h of perfusion with human plasma and after 1 day. The parameters studied were heamatological values of hepatic functions (GOT and GPT), induction of pro-inflammatory molecules and histopathological evaluation. Cytokines (IL-1 alpha, IL-1 beta, IL-6) induction and exposure of P-selectin on the endothelial cell surface, was only observed in control animals after 2 h of perfusion, as an early event. GOT and GPT values increase drammatically after 2 h perfusion and 1 day after the treatment according to the histopathological observation of liver damage. On the contrary, the livers of hDAF or hMCP transgenic mice, under the same treatment were significantly protected although the extent of this protection is dependent on the level of expression of transgenic human molecules

Discovery of chemotherapy-associated ovarian cancer antigens by interrogating memory T cells

According to the immunogenic cell death hypothesis, clinical chemotherapy treatments may result in CD8(+) and CD4(+) T-cell responses against tumor cells. To discover chemotherapy-associated antigens (CAAs), T cells derived from ovarian cancer (OC) patients (who had been treated with appropriate chemotherapy protocols) were interrogated with proteins isolated from primary OC cells. We screened for immunogenicity using two-dimensional electrophoresis gel-eluted OC proteins. Only the selected immunogenic antigens were molecularly characterized by mass-spectrometry-based analysis. Memory T cells that recognized antigens associated with apoptotic (but not live) OC cells were correlated with prolonged survival in response to chemotherapy, supporting the model of chemotherapy-induced apoptosis as an adjuvant of anti-tumor immunity. The strength of both memory CD4(+) and CD8(+) T cells producing either IFN- or IL-17 in response to apoptotic OC antigens was also significantly greater in Responders to chemotherapy than in nonresponders. Immunogenicity of some of these antigens was confirmed using recombinant proteins in an independent set of patients. The T-cell interrogation system represents a strategy of reverse tumor immunology that proposes to identify CAAs, which may then be validated as possible prognostic tumor biomarkers or cancer vaccines

Integral abutment bridges: Investigation of seismic soil-structure interaction effects by shaking table testing

In recent years there has been renewed interest on integral abutment bridges (IABs), mainly due to their low construction and maintenance cost. Owing to the monolithic connection between deck and abutments, there is strong soil-structure interaction between the bridge and the backfill under both thermal action and earthquake shaking. Although some of the regions where IABs are adopted qualify as highly seismic, there is limited knowledge as to their dynamic behaviour and vulnerability under strong ground shaking. To develop a better understanding on the seismic behaviour of IABs, an extensive experimental campaign involving over 75 shaking table&nbsp;tests and&nbsp;4800 time histories of recorded data, was carried out at EQUALS Laboratory, University of Bristol, under the auspices of EU-sponsored SERA project (Seismology and Earthquake Engineering Research Infrastructure Alliance for Europe). The tests were conducted on a 5&nbsp;m long shear stack mounted on a 3&nbsp;m × 3&nbsp;m 6-DOF earthquake simulator, focusing on interaction effects between a scaled bridge model, abutments, foundation piles and backfill soil. The study aims at (a) developing new scaling procedures for physical modelling of IABs, (b) investigating experimentally the potential benefits of adding compressible inclusions (CIs) between the abutment and the backfill and (c) exploring the influence of different types of connection between the abutment and the pile foundation. Results indicate that the CI reduces the accelerations on the bridge deck and the settlements in the backfill, while disconnecting piles from the cap decreases bending near the pile head