Clinical effects of preemptive intra-articular lidocaine, dexmedetomidine and lidocaine-dexmedetomidine administration in dogs undergoing arthroscopy.

This study investigated the perioperative effects of preemptive intra-articular lidocaine (L group), dexmedetomidine (D group) and lidocaine-dexmedetomidine (LD group) in dogs. Physiological variables were intraoperatively recorded at 5 min intervals starting from baseline (5 min before intra-articular injection). If nociception occurred, IV fentanyl was administered. Postoperative pain was assessed using the Short Form-Glasgow Composite Measure Pain Scale. Twenty-four dogs (eight in each group) were included in this prospective, randomized, masked clinical study. In the LD group, systolic arterial pressure significantly increased at T10 (P = 0.027), T15 (P = 0.021) and T20 (P = 0.022), compared with baseline. In the D and LD groups, mean arterial pressure significantly increased at T10 (P = 0.022; 0.024), T15 (P = 0.024; 0.09) and T20 (P = 0.019; 0.021), compared with baseline and diastolic arterial pressure significantly increased at T10 (P = 0.026; 0.047), T15 (P = 0.021; 0.023), T20 (P = 0.011; 0.012) and T25 (P = 0.019; 0.027), compared with baseline. In the LD group, heart rate significantly decreased at T5 (P = 0.031), T10 (P = 0.026) and T15 (P = 0.034), compared with baseline. Atrioventricular blocks appeared more frequently in the LD group than in L and D groups (P = 0.002). Group L received more fentanyl than the D and LD groups (P = 0.03). No differences in postoperative pain score were detected (P = 0.121). These findings suggested systemic absorption of intra-articular dexmedetomidine. Intra-articular lidocaine-dexmedetomidine was associated with a greater incidence of atrioventricular blocks. Intra-articular dexmedetomidine, alone and combined with lidocaine, provided better intraoperative analgesia than lidocaine in dogs undergoing arthroscopy, although the 12 h postoperative analgesic effect of the three treatments was similar.

A breaking down of the Mediterranean diet in the land where it was discovered. A cross sectional survey among the young generation of adolescents in the heart of Cilento, Southern Italy.

BACKGROUND: To investigate dietary habits among young people in the Mediterranean lands, exactly where the health benefits of the Mediterranean diet (MD) were discovered by Ancel Keys. STUDY DESIGN: A cross-sectional study design. METHODS: A 10-items food-frequency questionnaire was administered to 1117 students in the schools of the Cilento area. Adherence to the MD was appraised according to a scale of 0-10. A logistic regression model was used to identify possible factors associated with "Following an unhealthy diet". Results were expressed as Odds Ratio with 95% confidence interval and the level of significance was set at p<0.05. RESULTS: A percentage of 63.8 reached a score under six, indicating that the majority of the students did not respect the rules of the Mediterranean diet and only 36.2% (n. 371) exceeded a score of 6 adhering to it in varying degrees. At the logistic regression analysis smokers resulted to be affected by almost a double risk of getting away from the Mediterranean dietary pattern (OR = 1.93; CI 95% 1.44-2.57); on the contrary, those with a higher PCS12 (Physical Component Summary score) were in a lower risk to move away from the MD style (OR = 0.98; 95% CI = 0.96-0.99). CONCLUSIONS: Despite its increasing popularity worldwide, adherence to the MD model is decreasing. The new generation of young people does not adhere to the MD pattern although they live in the lands characterized by the tradition and culture of healthy diet and where the benefits from this pattern were initially discovered. Interventions and specific education about the healthy diet may be useful to recover student's dietary patterns as in the old eating tradition.

Photo-ionization of aluminum in a hot cavity for the selective production of exotic species project.

SPES (Selective Production of Exotic Species) is an Isotope Separation On-Line (ISOL) based accelerator facility that will be built in the Legnaro-Istituto Nazionale di Fisica Nucleare (INFN) Laboratory (Italy), intended to provide intense neutron-rich radioactive ion beams obtained by proton-induced fission of a uranium carbide (UCx) target. Besides this main target material, silicon carbide (SiC) will be the first to be used to deliver p-rich beams. This target will also validate the functionality of the SPES facility with aluminum beam as result of impinging SiC target with proton beam. In the past, off line studies on laser photoionization of aluminum have been performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro; a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. With the new Wien filter installed a better characterization of the ionization process in terms of efficiency was performed and results are discussed.

Ongoing characterization of the forced electron beam induced arc discharge ion source for the selective production of exotic species facility.

An intense research and development activity to finalize the design of the target ion source system for the selective production of exotic species (SPES) facility (operating according to the isotope separation on line technique) is at present ongoing at Legnaro National Laboratories. In particular, the characterization of ion sources in terms of ionization efficiency and transversal emittance is currently in progress, and a preliminary set of data is already available. In this work, the off-line ionization efficiency and emittance measurements for the SPES forced electron beam induced arc discharge ion source in the case of a stable Ar beam are presented in detail.

Laboratory tests of low density astrophysical nuclear equations of state.

Clustering in low density nuclear matter has been investigated using the NIMROD multidetector at Texas A&M University. Thermal coalescence modes were employed to extract densities, ρ, and temperatures, T, for evolving systems formed in collisions of 47A MeV (40)Ar+(112)Sn, (124)Sn and (64)Zn+(112)Sn, (124)Sn. The yields of d, t, (3)He, and (4)He have been determined at ρ=0.002 to 0.03 nucleons/fm(3) and T=5 to 11 MeV. The experimentally derived equilibrium constants for α particle production are compared with those predicted by a number of astrophysical equations of state. The data provide important new constraints on the model calculations.

Experimental determination of in-medium cluster binding energies and Mott points in nuclear matter.

In-medium binding energies and Mott points for d, t, 3He and α clusters in low-density nuclear matter have been determined at specific combinations of temperature and density in low-density nuclear matter produced in collisions of 47A MeV 40Ar and 64Zn projectiles with 112Sn and 124Sn target nuclei. The experimentally derived values of the in-medium modified binding energies are in good agreement with recent theoretical predictions based upon the implementation of Pauli blocking effects in a quantum statistical approach.

Prospects for advanced electron cyclotron resonance and electron beam ion source charge breeding methods for EURISOL.

As the most ambitious concept of isotope separation on line (ISOL) facility, EURISOL aims at producing unprecedented intensities of post-accelerated radioactive isotopes. Charge breeding, which transforms the charge state of radioactive beams from 1+ to an n+ charge state prior to post-acceleration, is a key technology which has to overcome the following challenges: high charge states for high energies, efficiency, rapidity and purity. On the roadmap to EURISOL, a dedicated R&D is being undertaken to push forward the frontiers of the present state-of-the-art techniques which use either electron cyclotron resonance or electron beam ion sources. We describe here the guidelines of this R&D.

Studies for aluminum photoionization in hot cavity for the selective production of exotic species project.

Selective production of exotic species (SPES) is an ISOL-based accelerator facility that will be built in the Legnaro INFN Laboratory (Italy), intended to provide an intense neutron-rich radioactive ion beams obtained by proton induced fission of an uranium carbide target. Beside this main target, a silicon carbide (SiC) target will the first to be used to deliver some p-rich beams. This target will validate also the functionality of the SPES facility with aluminum beam as result of hitting SiC target with protons. In the past off-line studies on laser photoionization of aluminum have performed in Pavia Spectroscopy Laboratory and in Laboratori Nazionali di Legnaro where, recently, a XeCl excimer laser was installed in order to test the laser ionization in the SPES hot cavity. Results are promising to justify further studies with this technique, aiming a better characterization of the SPES ion extraction capability under laser photoionization.

Radiation damage evaluation on concrete within a facility for Selective Production of Exotic Species (SPES Project), Italy.

Concrete is commonly used as a biological shield against nuclear radiation. As long as, in the design of nuclear facilities, its load carrying capacity is required together with its shielding properties, changes in the mechanical properties due to nuclear radiation are of particular significance and may have to be taken into account in such circumstances. The study presented here allows for reaching first evidences on the behavior of concrete when exposed to nuclear radiation in order to evaluate the consequent effect on the mechanical field, by means of a proper definition of the radiation damage, strictly connected with the strength properties of the building material. Experimental evidences on the decay of the mechanical modulus of concrete have allowed for implementing the required damage law within a 3D F.E. research code which accounts for the coupling among moisture, heat transfer and the mechanical field in concrete treated as a fully coupled porous medium. The development of the damage front in a concrete shielding wall is analyzed under neutron radiation and results within the wall thickness are reported for long-term radiation spans and several concrete mixtures in order to discuss the resulting shielding properties.

Nucleic Acid, Antibody, and Virus Culture Methods to Detect Xenotropic MLV-Related Virus in Human Blood Samples.

The MLV-related retrovirus, XMRV, was recently identified and reported to be associated with both prostate cancer and chronic fatigue syndrome. At the National Cancer Institute-Frederick, MD (NCI-Frederick), we developed highly sensitive methods to detect XMRV nucleic acids, antibodies, and replication competent virus. Analysis of XMRV-spiked samples and/or specimens from two pigtail macaques experimentally inoculated with 22Rv1 cell-derived XMRV confirmed the ability of the assays used to detect XMRV RNA and DNA, and culture isolatable virus when present, along with XMRV reactive antibody responses. Using these assays, we did not detect evidence of XMRV in blood samples (N = 134) or prostate specimens (N = 19) from two independent cohorts of patients with prostate cancer. Previous studies detected XMRV in prostate tissues. In the present study, we primarily investigated the levels of XMRV in blood plasma samples collected from patients with prostate cancer. These results demonstrate that while XMRV-related assays developed at the NCI-Frederick can readily measure XMRV nucleic acids, antibodies, and replication competent virus, no evidence of XMRV was found in the blood of patients with prostate cancer.

Stimulation of TH1 response by Helicobacter pylori neutrophil activating protein decreases the protective role of IgE and eosinophils in experimental trichinellosis.

Th2 responses seem to play an important role in defence against Trichinella spiralis (Ts). The neutrophil Activating protein of Helicobacter pylori (HP-NAP), that induces IL-12, and IL-23 expression and shifts to Th1 allergen-specific Th2 cells in vitro was used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower (p < 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r -0.617, p = 0.0013 and HP-NAP-treated: r -0.678, p = 0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r -0.390, p = 0.0592 and r -0.803, p = 0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivo by HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection.

Mutations in TAZ/WWTR1, a co-activator of NKX2.1 and PAX8 are not a frequent cause of thyroid dysgenesis.

AIM: In 80-85% of cases, congenital hypothyroidism is associated with thyroid dysgenesis (TD), but only in a small percentage of cases mutations in thyroid transcription factors (NKX2.1, PAX8, FOXE1, and NKX2.5) have been associated with the disease. Several studies demonstrated that the activity of the transcription factors can be modulated by the interaction with other proteins, such as coactivators and co-repressors, and TAZ (transcriptional co-activator with PDZ-binding motif or WWTR1) is a co-activator interacting with both NKX2.1 and PAX8. In the present study we investigate the role of TAZ in the pathogenesis of TD. MATERIAL AND METHODS: By Single Stranded Conformational Polymorphism, we screened the entire TAZ coding sequence for mutations in 96 patients with TD and in 96 normal controls. RESULTS: No mutations were found in patients and controls, but we found several polymorphisms in both groups. No significant differences could be demonstrated in the prevalence of the mutations between patients and controls. CONCLUSIONS: Our data indicate that TAZ mutations are not a cause of TD in the series of patients studied.

Plant-derived recombinant F1, V, and F1-V fusion antigens of Yersinia pestis activate human cells of the innate and adaptive immune system.

Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamiana administered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent Y. pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-alpha, IL-12, IL-10, IL-1beta, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from Y. pestis infection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y. pestis infection.

Moraxella catarrhalis-specific Th1 cells in BAL fluids of chronic obstructive pulmonary disease patients.

In chronic obstructive pulmonary disease (COPD) patients airway mucosa is infiltrated by macrophages and T lymphocytes, potentially reactive to pathogens. We studied the antigen-specificity and the effector functions of in vivo activated T lymphocytes isolated from BAL (Bronchoalveolar lavage) of 5 Moraxella catarrhalis (Mc)-infected and 5 Mc-non-infected COPD patients. Mc-specific T cells were detected only in BAL or peripheral blood of Moraxella catarrhalis-infected patients. The majority of BAL Mc-specific T cells expressed the T helper type 1 (Th1) cytokine profile with high cytotoxic and pro-apoptotic activity. Upon antigen stimulation, all Mc-specific T clones were able to help the immunoglobulin production by autologous B cells and the MMP (Matrix MetalloProteinase)-12 activity by monocytes. Our results suggest a role for Th1-driven response to Moraxella catarrhalis in the genesis of COPD.

The complexity of the CD4 T-cell responses: old and new T-cell subsets.

The T-cell compartment of the immune system reacts to an enormous variety of antigens, including self antigens, due to its a wide repertoire of T-cell clones. Self-reactive T cells undergo a negative selection process resulting in apoptosis of T cells with high affinity for self-peptides. Self-reactive T cells escaped to negative selection are then controlled by natural T regulatory (Treg) cells. Regulation also controls excessive effector T-cell responses. Three types of effector T cells are recognized: T helper 1 (Th1) cells, which protect against intracellular bacteria; Th2 cells, which play a role against parasites; Th17 cells, which would face extracellular bacteria, but also are involved in autoimmunity. Effector T-cell polarization is determined by the complex interaction of antigen-presenting cells with naive T cells and involves a multitude of factors, including the dominant cytokine environment, costimulatory molecules, type and load of antigen presented and signaling cascades. The decision for the immune response to go in a certain direction is based not onto one signal alone, rather onto many different elements acting synergistically, antagonistically and through feedback loops leading to activation of Th1, Th2, or Th17 responses. Both Th1 and Th2 can be suppressed by adaptive Treg cells through contact-dependent mechanisms and/or cytokines.

Human gastric epithelium produces IL-4 and IL-4delta2 isoform only upon Helicobacter pylori infection.

Recent evidence suggests that interleukin-4 (IL-4) is related to mucosal tolerance by which an injurious immune response is prevented, suppressed or shifted to a non-injurious response. We investigated the expression of IL-4 and its splice variant isoform IL-4delta2 in gastric epithelial cells of healthy subjects and gastritis patients infected with Helicobacter pylori (H. pylori) with or without the cag pathogenicity island (cag-PAI). IL-4 and IL-4delta2 mRNAs were evaluated in microdissected gastric epithelium and in AGS cell lines co-cultured with H. pylori B128 or SS1 strains. IL-4 mRNA was consistently detected in microdissected gastric epithelial cells from healthy subjects. The IL-4 mRNA expression was low in H. pylori?infected patients, and markedly reduced in cag-PAI-positive ones. IL-4delta2 mRNA was expressed on gastric epithelium of H. pylori-infected patients, but not in healthy subjects. The IL-4delta2 expression was lower in cag-PAI-positive than in cag-PAI-negative H. pylori infected patients. AGS cells also produced IL-4 mRNA upon SS1 strain stimulation, whereas IL-4delta2 mRNA expression was detected in AGS co-cultured with either SS1 or B128 strains. An inverse correlation was documented between IL-4 and IL-4delta2 mRNA expression by microdissected gastric epithelial cells and the score of gastritis. IL-4, but not IL-4delta2, is expressed by gastric epithelium of healthy subjects, whereas IL-4delta2 and lesser IL-4 mRNA are detectable in the gastric epithelium of H. pylori-infected patients. Data suggest that gastric epithelial cells might regulate the balance between tolerance and immune response by the fine tuning of IL-4 and IL-4delta2 expression.

Soluble CD30 and lymphocyte activation gene-3 (CD223), as potential serological markers of T helper-type cytokine response induced by acellular pertussis vaccine.

T cell responses are involved in vaccine-induced immunity to pertussis but no easy-to-monitor, serological markers are available to assess these responses. The lymphocyte activation gene-3 (CD223) molecule is present on, and released by, activated T helper (Th) 1 cells, whereas CD30 molecules have been associated with Th2 immune responses. Starting from the recent knowledge of the cytokine profile induced by pertussis vaccination, we examined the levels of soluble (s)CD223 and sCD30 proteins in child recipients of acellular pertussis (aP) and diphtheria-tetanus (DT) vaccines and in children receiving DT vaccine only, as control. The correlation of the two proteins with specific antibody and T cell responses was assessed. The main findings are: i) sCD223 and sCD30 levels are inversely related, suggesting that the two markers are the expression of different and counter-regulated T-cell responses; ii) sCD30 level correlated with induction of T cell proliferation to pertussis vaccine antigens and antibody response to pertussis toxin. Overall, sCD30 and sCD223 levels seem to be promising candidate markers to assess the induction of Th-type responses in vaccine recipients.

Serological markers of pulmonary tuberculosis and of response to anti-tuberculosis treatment in a patient population in Guinea.

The aim of the study was to evaluate serological correlates of active tuberculosis and of response to antituberculosis treatment in a cohort of HIV-negative patients with pulmonary tuberculosis studied at diagnosis and during treatment at the Service de Pneumo-Phtisiologie, Centre Hospitalier-Universitaire Ignace Deen, Conakry, Republic of Guinea. Two similar cohorts of HIV-negative healthy households of patients and healthy community controls were included in the study. Plasma samples were obtained from 168 untreated tuberculosis patients, 167 healthy household controls, and 168 healthy community controls. Serial plasma samples were also obtained from the tuberculosis patients at 2 and 8 months after initiation of chemotherapy. IgG antibody levels were measured by an enzyme-linked immunosorbent assay (ELISA) using ten purified M. tuberculosis antigens. ELISA results were analysed by comparing geometric means of data. Of the ten antigens tested, five (14kDa Ag, 19kDa Ag, AlaDH, MS, and MPT83) elicited similar antibody responses in untreated TB patients and controls. In contrast, levels of three antibodies (ESAT-6, LAM, and 38kDa Ag) were higher in untreated TB patients than in household or community controls (p<0.0001). Levels were higher in untreated patients than in community controls also for the anti-Rv2626c antibody (p = 0.0001) and, at a lower significance level, for the anti-FdxA antibody (p<0.025). Antibody levels against ESAT-6 and Rv2626c decreased during therapy, while antibody levels to the 38 kDa antigen and LAM increased during therapy; FdxA antibody levels did not vary with treatment. Neither severity of presentation nor chest X-ray patterns affected levels of these antibodies before treatment. In contrast, after the 8-month therapeutic course, patients who presented with moderate/severe disease had higher levels of anti-ESAT-6, anti-FdxA, and anti-38kDa antibodies than those of patients with mild disease onset. Patients with bilateral lung lesions had significantly higher anti-38kDa and anti-LAM levels, both at diagnosis and after 8-month treatment, than patients with lesions involving only one lung. Antibodies to alanine dehydrogenase and malate synthetase measured at initiation of treatment were higher in tuberculosis patients who subsequently failed therapy than in those who were cured. The main conclusions of the study are: a) plasma levels of antibodies to a number of M. tuberculosis represent serological correlates of active disease; b) these correlates are affected in an antigen-specific fashion by anti-tuberculosis treatment; c) particular serological markers may be predictive of treatment outcome.