A canine vaccine against Leptospira serovars Icterohaemorrhagiae, Canicola and Grippotyphosa provides cross protection against Leptospira serovar Copenhageni.

Efficacy of the Leptospira components of multivalent vaccine DAPPi-L was previously demonstrated against virulent challenge with three serovars of Leptospira interrogans (Canicola, Icterohaemorrhagiae and Grippotyphosa) carried out 14 days after primary vaccination. In this study we demonstrate that this vaccine provides, two weeks after vaccination, an additional protection (prevention of mortality, clinical signs, renal infection, bacterial excretion, renal carriage and renal lesions) against fatal leptospirosis due to Leptospira interrogans serovar Copenhageni (serovar of major medical importance).

Resting state brain connectivity patterns before eventual relapse into cocaine abuse.

According to recent theories, drug addicted patients suffer of an impaired response inhibition and salience attribution (I-RISA) together with a perturbed connectivity between the nuclei accumbens (NAcs) and the orbito-prefrontal (oPFC) and dorsal prefrontal (dPFC) cortices, brain regions associated with motivation and cognitive control. To empirically test these assumptions, we evaluated the (neuro)psychological trait and the functional organization of the resting state brain networks associated with the NAcs in 18 former cocaine abusers (FCAs), while being in drug abstinence since 5 months. The psychological data were grouped into three empirical variables related with emotion regulation, emotion awareness and strategic and controlled behaviour. Comparison of the resting state patterns between the entire sample of FCAs and 19 controls revealed a reduction of functional connectivity between the NAcs and the dPFC and enhanced connectivity between the NAcs and the dorsal-striatum. In the 8 FCAs who relapsed into cocaine use after 3 months, the level of functional connectivity between the NAcs and dPFC was lower than the functional connectivity estimated in the group of patients that did not relapsed. Finally, in the entire sample of FCAs, the higher the connectivity between the NAc and the oPFC the lower was the level of strategic and controlled behaviour. Taken together, these results are compatible with models of the interactions between the NAcs, the dorsal striatum and frontal cortices in the I-RISA syndrome, showing that such interactions are particularly perturbed in patients at greater risk of relapse into cocaine abuse.

Laser-induced disaggregation of TiO2 nanofillers for uniform nanocomposites.

Exploiting the intrinsic photosensitivity of TiO2 nanoparticles, we demonstrated how ultraviolet (UV) pulsed laser irradiation of acrylate polymer nanocomposite solutions can separate the initial clusters of these colloidal semiconductor nanorods into clearly distinct units. From the irradiated solutions, optically clear nanocomposite films are obtained which exhibit enhanced optical properties with respect to the nanocomposites obtained without previous UV treatment.

Zinc transporter (ZnT)8(186-194) is an immunodominant CD8+ T cell epitope in HLA-A2+ type 1 diabetic patients.

AIMS/HYPOTHESIS: Anti-zinc transporter (ZnT)8 autoantibodies are commonly detected in type 1 diabetic patients. We hypothesised that ZnT8 is also recognised by CD8(+) T cells and aimed to identify HLA-A2 (A*02:01)-restricted epitope targets. METHODS: Candidate epitopes were selected by ZnT8 plasmid DNA immunisation of HLA-A2/DQ8 transgenic mice and tested for T cell recognition in peripheral blood mononuclear cells of type 1 diabetic, type 2 diabetic and healthy participants by IFN-γ enzyme-linked immunospot. RESULTS: White HLA-A2(+) adults (83%) and children (60%) with type 1 diabetes displayed ZnT8-reactive CD8(+) T cells that recognised a single ZnT8(186-194) (VAANIVLTV) epitope. This ZnT8(186-194)-reactive fraction accounted for 50% to 53% of total ZnT8-specific CD8(+) T cells. Another sequence, ZnT8(153-161) (VVTGVLVYL), was recognised in 20% and 25% of type 1 diabetic adults and children, respectively. Both epitopes were type 1 diabetes-specific, being marginally recognised by type 2 diabetic and healthy participants (7-12% for ZnT8(186-194), 0% for ZnT8(153-161)). CONCLUSIONS/INTERPRETATION: ZnT8-reactive CD8(+) T cells are predominantly directed against the ZnT8(186-194) epitope and are detected in a majority of type 1 diabetic patients. The exceptional immunodominance of ZnT8(186-194) may point to common environmental triggers precipitating beta cell autoimmunity.

Immunology of Diabetes Society T-Cell Workshop: HLA class I tetramer-directed epitope validation initiative T-Cell Workshop Report-HLA Class I Tetramer Validation Initiative.

BACKGROUND: Identification of T-cell reactivity to ß-cell antigen epitopes is an important goal for studying pathogenesis and for designing and monitoring of immunotherapeutic interventions in type 1 diabetes (T1D). METHODS: We performed a multicentre validation of known human leukocyte antigen (HLA) class I CD8+ T-cell epitopes. To this end, peripheral blood T-cell responses were measured in 35 recently (<2 years) diagnosed HLA-A*02:01+ T1D patients using blind-coded HLA-A2 tetramers (TMrs) and pentamers (PMrs), encompassing two epitopes of preproinsulin (PPI; PPIA12-20 and PPIB10-18) and two epitopes of glutamic acid decarboxylase (GAD; GAD114-122 and GAD536-545). We also compared the readout of TMrs and PMrs with a CD8+ T-cell interferon-γ enzyme-linked immunospot assay. RESULTS: Despite the minute frequencies of autoreactive cells detected by TMrs/PMrs, most (73-77%) T1D patients had responses to one or more of the epitopes used. All four epitopes were recognized by T1D patients, with a prevalence ranging from 5 to 25%. TMrs and PMrs detected more positive responses to the ß-cell epitopes than CD8+ T-cell interferon-γ enzyme-linked immunospot. However, concordance between positive responses to TMrs and PMrs was limited. CONCLUSIONS: Using a multicentre blind-coded setup and three different T-cell assays, we have validated PPI and GAD epitopes as commonly recognized CD8+ T-cell targets in recently diagnosed T1D patients. Both TMrs and PMrs showed higher detection sensitivity than the CD8+ T-cell interferon-γ enzyme-linked immunospot assay. However, there are some important methodological issues that need to be addressed in using these sensitive techniques for detecting low frequency responses.

Comparison of cryopreservation methods on T-cell responses to islet and control antigens from type 1 diabetic patients and controls.

BACKGROUND: Type 1 diabetes (T1D) is a cell-mediated autoimmune disease characterized by destruction of the pancreatic islet cells. The use of cryopreserved cells is preferable to the use of freshly isolated cells to monitor clinical trials to decrease assay and laboratory variability. METHODS: The T-Cell Workshop Committee of the Immunology of Diabetes Society compared two widely accepted T-cell freezing protocols (warm and cold) to freshly isolated peripheral blood mononuclear cells from patients with T1D and controls in terms of recovery, viability, cell subset composition, and performance in functional assays currently in use in T1D-related research. Nine laboratories participated in the study with four different functional assays included. RESULTS: The cold freezing method yielded higher recovery and viability compared with the warm freezing method. Irrespective of freezing protocol, B cells and CD8+ T cells were enriched, monocyte fraction decreased, and islet antigen-reactive responses were lower in frozen versus fresh cells. However, these results need to take in to account that the overall response to islet autoantigens was low in some assays. CONCLUSIONS: In the current study, none of the tested T-cell functional assays performed well using frozen samples. More research is required to identify a freezing method and a T-cell functional assay that will produce responses in patients with T1D comparable to responses using fresh peripheral blood mononuclear cells.

[Risk factors and prevalence of asthma and rhinitis among primary school children in Lisbon]. / Factores de risco e prevalência de asma e rinite em crianças em idade escolar em Lisboa.

AIMS: A cross-sectional study was carried out with the objective of identifying nutrition habits and housing conditions as risk factors for respiratory problems in schoolchildren in Lisbon. MATERIAL AND METHODS: Between October and December 2008, parents of 900 students of the basic schools of Lisbon were invited to answer a questionnaire of the International Study of Asthma and Allergies in Childhood Program (ISAAC). The response rate was 40%. Logistic regression was used in the analysis of results. RESULTS: The prevalence of asthma, allergic rhinitis and wheeze was 5.6%, 43.0% and 43.3%, respectively. Risk factors independently associated with asthma were wheezing attacks, and dry cough at night not related to common cold in the last 12 months. Wheezing crises were found to affect children daily activities. Risk factors for wheeze were hay fever and the presence of a pet at home. A risk factor for rhinitis was cough at night. The frequent consumption of egg was also associated with increased risk of rhinitis. CONCLUSION: Contrarily to asthma, the prevalence of allergic rhinitis and wheeze increased in comparison with previous ISAAC studies. Wheezing attacks were associated with asthma and hay fever was identified as a risk factor of manifesting wheezing symptoms. Having pets at home was pointed out as a significant risk factor for rhinitis, but not smoking exposure, mould, plush toys, diet (except egg consumption), breastfeeding or other conditions.

23Na NMR study of the interaction between hyaluronan and the bications Ca(++), Mg(++) and Cu(++).

The relaxation rate R = pi Delta nu(1/2) of the quadrupolar (23)Na nucleus was measured at pH approximately 7 using a 200 MHz NMR spectrometer with a view to observe the interaction between hyaluronan and its natural counterion Na(+) and the bications Ca(++), Mg(++) and Cu(++). An interpretation of our results, by means of the "entropy of fluctuations" concept of Na(+), is presented. We show that Cu(++) ions are more effective than Ca(++) and Mg(++). A possible model of complexation of Cu(++) in a cage formed by the 1-4 glycosidic bond, the carboxylate side-chain and the acetoamide side-chain is proposed, according to electrostatic potential computations using the ZINDO1 quantum semi empirical method.

Reproducibility of neurophysiological and myometric measurement in the ulnar nerve-abductor digiti minimi system.

Reliability in strength and neurophysiological measurements is important in evaluating progression of neuromuscular diseases. No data are available on the variability of neurophysiological parameters as compared with maximal voluntary isometric contraction (MVIC) in the same muscles, in healthy subjects. A control population of 26 healthy subjects was studied twice on different days. We evaluated the reliability of neurophysiological parameters obtained from bilateral ulnar nerve stimulation, recording the response over the abductor digiti minimi (ADM) muscle, including distal motor latency, compound muscle potential amplitude and area, F-wave frequency and mean F-wave latency, and the derived neurophysiological index that we have described previously. MVIC force was measured in each session in both ADM muscles. The variances between the grouped data obtained in the two recording sessions were identical, indicating a low intrinsic variability with this experimental methodology. Comparison of the mean values obtained in the two sessions revealed no statistically significant differences. The reliability of these neurophysiological and strength measurements in the same nerve/muscle system suggests they may be useful in comparing the dynamics of weakness and neurophysiological change in neuromuscular disease.

An unusual case of sundown syndrome subsequent to a traumatic head injury.

An unusual case of sundown syndrome is here reported, in which a bilingual patient would involuntarily change languages at sunset. Numerous theories have been advanced in attempting to account for sundowning. Cameron has suggested that nocturnal delirium was based on an inability to maintain a spatial image without the assistance of repeated visualization. Kral and Wolanin and Phillips have argued for a more psychogenic account, by stating that psychosocial stressors may, in concert with impaired cognitive functioning, account for sundowning. The present case concerns a 42-year-old white male who in January 1989 suffered a closed head injury. A thorough personal history as well as a detailed examination of the patient's daily activities allowed us to account for the unusual manner in which the sundowning manifested itself. The uniqueness of this case allows us to underscore both the psychological as well as environmental and neurological factors involved in sundowning. Thus, we have as a consequence been able to synthesize the seemingly disparate accounts of both Cameron and more recent published literature.

Smooth periodic eye movements can entrain perceptual alternation.

The reversal signals and eye movements of three subjects looking at a Necker cube that moved sinusoidally in the subject's field of view were recorded. The aim of the experiment was to provide evidence of possible synchronisation of perceptual alternation with smooth periodic eye movements. The occurrence of synchronisation was demonstrated for a proper choice of the eye oscillation period by both a sharp reduction in the fluctuations of the reversal time and a change in the mean value of this parameter. Such variations resulted in a close match of the mean reversal time to a multiple of the eye oscillation period. Further, inversions of the direction of eye movements elicited pattern reversals in a systematic way, characteristic for each subject. The described phenomenon, which is a typical example of nonlinear-resonant behaviour, stresses a new important aspect of the complex interaction pattern relating pursuit eye movements to visual perception.

Eye movements and reversal rates of ambiguous patterns.

To study the influence of eye movements on the time course of perceptual alternation of ambiguous patterns, we recorded the reversal signals and eye movements of four subjects, during prolonged observations of a Necker cube, under three experimental conditions: unrestricted normal viewing, instruction-restricted normal viewing, and imperfectly stabilized viewing. An important decrease in the frequency of saccadic eye movements and a significant increase in the reversal rates were shown by all subjects under imperfectly stabilized viewing over the normal unrestricted viewing. Moreover, three out of four subjects showed a significant decrease in their reversal rates when changing from the normal to instruction-restricted viewing. Results are discussed in terms of the role and time cost of scanning eye movements in perceptual processes.

Limit cycle oscillations of the human eye.

The altered feedback technique is very suited to display nonlinearities of the human smooth pursuit system. In fact, when the gain of the retinal feedback path is raised, for the horizontal channel, above its normal unitary negative value, a threshold is met beyond which sustained horizontal self-excited smooth oscillations of the eye can be observed, which point out the existence of a stable limit cycle. Furthermore, the characterizing features of both the transient and steady state show a well defined dependence on the total feedback factor K. In particular, the analytical dependence on K of the amplitude and frequency of limit cycle oscillations can be derived. Implications of the experiment with respect to the mathematical modelling of the system are discussed.