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Motivation Omics technologies have the potential to facilitate the discovery of new biomarkers. However, only few omics-derived biomarkers have been successfully translated into clinical applications to date. Feature selection is a crucial step in this process that identifies small sets of features with high predictive power. Models consisting of a limited number of features are not only more robust in analytical terms, but also ensure cost effectiveness and clinical translatability of new biomarker panels. Here we introduce GARBO, a novel multi-island adaptive genetic algorithm to simultaneously optimize accuracy and set size in omics-driven biomarker discovery problems. Results Compared to existing methods, GARBO enables the identification of biomarker sets that best optimize the trade-off between classification accuracy and number of biomarkers. We tested GARBO and six alternative selection methods with two high relevant topics in precision medicine: cancer patient stratification and drug sensitivity prediction. We found multivariate biomarker models from different omics data types such as mRNA, miRNA, copy number variation, mutation and DNA methylation. The top performing models were evaluated by using two different strategies: the Pareto-based selection, and the weighted sum between accuracy and set size (w  = 0.5). Pareto-based preferences show the ability of the proposed algorithm to search minimal subsets of relevant features that can be used to model accurate random forest-based classification systems. Moreover, GARBO systematically identified, on larger omics data types, such as gene expression and DNA methylation, biomarker panels exhibiting higher classification accuracy or employing a number of features much lower than those discovered with other methods. These results were confirmed on independent datasets. Availability and implementation github.com/Greco-Lab/GARBO. Contact dario.greco@tuni.fi Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background/Study context: Posture and gait are complex sensorimotor functions affected by age. These difficulties are particularly apparent when performing cognitively demanding tasks. Characterizing the functional organization of brain networks involved in these associations remains a challenge because of the incompatibility of brain imagery techniques with gross body movements. The present study aimed at testing whether resting-state functional connectivity of sensorimotor networks is associated with posture and gait performance recorded offline, in young and older adults. Methods: Young (n = 12, mean = 24.1 y/o) and older (n = 14, mean = 65.6 y/o) healthy adults were tested for stability of their posture and gait. Four hours later, anatomical and functional brain imaging data were collected with Magnetic Resonance Imaging (MRI). Bilateral precentral and postcentral gyri were used as seeds in a graph theory analysis focused on global and local efficiency. The possible association between these data and posture and gait performance was examined. Results: Both samples presented similar sensorimotor graphs, but with different global and local efficiencies (small world properties). The association between the networks' graph measures and posture and gait performance also differed across groups: local efficiency was correlated with gait stability in challenging conditions in older adults, but not in young adults. Conclusion: This exploratory study suggests that combining analyses of functional networks and offline body movement may provide important information about motor function. In older adults, the association between graph properties of the sensorimotor network and gait performance in challenging conditions may be indicative of compensatory processes. Prospective studies involving more subjects with a larger age range are warranted. [ABSTRACT FROM AUTHOR]

Background: Spatial normalization of brain images, a prerequisite for voxel based morphometry analysis, may account for the large variability of the volumetric data in medication overuse headache (MOH); possibly because this disease concerns patients differing on both sex and age, and hence with different brain size and shape. Methods: The present study aimed at providing a subject-based analysis of macrostructure using a native space volumes segmentation (Freesurfer), and microstructure using a region of interest (ROI: i.e. hippocampus) tractography approach in MOH patients. Results: The results show that MOH patients had decreased volumes of left hemisphere temporal gyri (temporal superior, fusiform) and occipital middle gyrus, together with an increased volume of the left inferior (temporal) lateral ventricle. The left temporal volume was negatively correlated with depression score and medication dependence parameters. Seed-based tractography of the hippocampus revealed a decreased number of reconstructed fibers passing through the left hippocampus. Conclusion: To our knowledge, these alterations have not been described with methods involving brain normalization, and they indicate that left hemisphere temporal areas, including the hippocampus, may play a role in MOH pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Several imaging studies have identified localized anatomical and functional brain changes in medication-overuse headache (MOH).Objective: The objective of this article is to evaluate whole-brain functional connectivity at rest together with voxel-based morphometry in MOH patients, in comparison with episodic migraine (EM) patients and healthy controls (HCs).Methods: Anatomical MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17 and 9, respectively), EM patients (n = 18 and 15, respectively) and HCs (n = 17 and 17). SPM8 was used to analyze voxel-based morphometry and seed (left precuneus) to voxel connectivity data in the whole brain.Results: Functional connectivity at rest was altered in MOH patients. Connectivity was decreased between precuneus and regions of the default-mode network (frontal and parietal cortices), but increased between precuneus and hippocampal/temporal areas. These functional modifications were not accompanied by significant gross morphological changes. Furthermore, connectivity between precuneus and frontal areas in MOH was negatively correlated with migraine duration and positively correlated with self-evaluation of medication dependence. Gray matter volumes of frontal regions, precuneus and hippocampus were also negatively related to migraine duration. Functional connectivity within the default-mode network appeared to predict anxiety scores of MOH patients while gray matter volumes in this network predicted their depression scores.Conclusions: Our data suggest that MOH is associated with functional alterations within intrinsic brain networks rather than with macrostructural changes. They also support the view that dependence-related processes might play a prominent role in its development and maintenance. [ABSTRACT FROM AUTHOR]

The reticular groove mucosa of adult cattle, buffalo and sheep was investigated by histochemical and immunocytochemical techniques. Intense NADPH-d staining was observed in the folds of the epithelium mucosa and at the bottom of the reticular groove in all domestic ruminants studied. The NADPH-d staining showed that the innervations of the tunica muscularis of the reticular groove lip were composed of nerve corpuscles, nerve fibres and nerve cells of the mucosa epithelium. SEM analysis showed an intense nitric oxide synthase ( NOS) I immunoreactivity in deep and medium cellular layers. It is interesting to note that the same morphologies were observed in samples of the mucosa epithelium, and of the tunica muscularis processed by NADPH-d and in those processed by immunogold techniques. This study has demonstrated that nitric oxide ( NO) is involved in the rumination activity and that it plays a double role in this activity in the reticular groove of all domestic ruminants studied: (1) NO plays a role similar to the one it has in the mucosa epithelium of all the other compartments of the ruminant forestomach, (2) The lip sections of the reticular groove has shown abundant innervations that may indirectly coordinate and control the forestomach motility through the direct activation of the nitrergic (nitroxidergic) nerve cells and nerve fibres. [ABSTRACT FROM AUTHOR]

Abstract: The rodent olfactory bulb sends direct projections to the piriform cortex and to two structures intimately implicated in memory processes, the entorhinal cortex and the amygdala. The piriform cortex has monosynaptic projections with the amygdala and the piriform cortex and is therefore in a position to modulate olfactory input either directly in the piriform cortex, or via the amygdala. In order to investigate this hypothesis, field potential signals induced in anesthetized rats by electrical stimulation of the olfactory bulb or the entorhinal cortex were recorded simultaneously in the piriform cortex (anterior part and posterior part) and the amygdala (basolateral nucleus and cortical nucleus). Single-site paired-pulse stimulation was used to assess the time courses of short-term inhibition and facilitation in each recording site in response to electrical stimulation of the olfactory bulb and entorhinal cortex. Paired-pulse stimulation of the olfactory bulb induced homosynaptic inhibition for short interpulse interpulse intervals (20–30 ms) in all the recording sites, with a significantly lower degree of inhibition in the anterior piriform cortex than in the other structures. At longer intervals (40–80 ms), paired-pulse facilitation was observed in all the structures. Paired-pulse stimulation of the entorhinal cortex mainly resulted in inhibition for the shortest interval duration (20 ms) in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. Double-site paired-pulse stimulation was then applied to determine if stimulation of the entorhinal cortex can modulate responses to olfactory bulb stimulation. For short interpulse intervals (20 ms) heterosynaptic inhibition was observed in anterior piriform cortex, posterior piriform cortex and amygdala basolateral but not cortical nucleus. The level of inhibition was greater in the basolateral nucleus than in the other structures. Taken together these data suggest that the entorhinal cortex exerts a main inhibitory effect on the olfactory input via the amygdala basolateral nucleus and to a lesser extent the piriform cortex. The potential role of these effects on the processing of olfactory information is discussed. [Copyright &y& Elsevier]

The present investigation was designed lo detect abnormalities in CMI and the presence of polyclonally activated B cells in patients with HBV positive CAH. We studied the peripheral levels and ³H-thymidine incorporation of three lymphocyte subsets: B lymphocytes, as well as two T cell subsets that are either active or late rosetters with high and low affinity receptors respectively for sheep red blood cells (SRBC). In patients the level of peripheral T active cells was decreased, but they exhibited elevated B cell activation. There was also a significant correlation between the decreased levels of T active cells and increased ³H-thymidine incorporation by B lymphocytes. Taken together, our results are consistent with the hypothesis that patients with HBV positive CAH have a severe impairment of T cell function that may lead to an abnormal B cell activation. The increased B cell activity may account for the presence of circulating immune complexes and the variety of autoantibodies often observed in patients with HBV positive CAH. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article related to food allergies by K. Soares-Weiser and other published in a previous issue of the periodical is presented.

Objectif: La perte cutanée suite aux brulures profondes ou aux traumatismes est fréquente chez l’enfant. La greffe de peau fine est utilisée dans la reconstruction cutanée avec le désavantage d’être moins souple et de se rétracter souvent. Nous décrivons notre expérience avec Matriderm®, un supplément dermique à base de collagène-élastine, appliqué durant la même intervention que la greffe de peau fine. Patients et Méthodes: Avec l’accord du comité d’éthique nous avons revu les dossiers des enfants traités par Matriderm® entre 2007 et 2010. 10 patients ont été traités de façon standardisée par Matriderm® fixé par colle de fibrine, suivi de la greffe de peau fine et pansement à pression négative (VAC®). La greffe était prélevée au cuir chevelu. Résultat: La prise de greffe était en moyenne > 95 % avec une guérison stable et une peau souple au suivi (moyenne 10,4 mois).Un patient a été regreffé avec succès après surinfection et perte de 50 % de la greffe. Un patient a développé des cicatrices chéloïdes après un résultat initial excellent. Conclusion: Dans notre expérience Matriderm® semble être un traitement sûr avec l’avantage de la possibilité d’application simultanée avec la greffe cutanée. Il s’agit de la première publication de Matriderm® chez l’enfant et nos résultats sont favorables. [ABSTRACT FROM AUTHOR]

Objectif: La plicature de l’anthélix lors d’otoplastie est parfois décevante, car trop marquée et visible. Cette étude rapporte l’intérêt d’associer à la technique de Mustardé, un lambeau sous-cutané à pédicule supérieur. Méthodes: Analyse rétrospective des cas opérés par le même chirurgien depuis 2007, et comparée à la technique classique de Mustardé sans lambeau associé, pratiquée auparavant. La satisfaction des patients et du chirurgien ont été répertoriées, à 6 mois post-opératoire, photos à l’appui. Technique / Résultats: Le lambeau à pédicule supérieur est prélevé dans le tissu sous-cutané, immédiatement après l’incision cutanée postérieure. Il est positionné et fixé sous les points dans l’espace postérieur obtenu après plicature de l’anthélix selon Mustardé. 63 otoplasties ont été réalisées avec cette technique. 100 % des patients étaient satisfaits. Un granulome sur fil a été la seule complication notée. L’aspect final parait plus satisfaisant et plus naturel que sans lambeau, la présence de tissu sous-cutanée sous la plicature de l’anthélix permettant d’adoucir l’angle de correction. Conclusion: L’utilisation de ce lambeau nous parait utile et intéressante à connaitre afin d’obtenir une correction plus harmonieuse et plus naturelle de l’anthélix. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Latent inhibition (LI) refers to the decrease in conditioned response induced by the repeated non-reinforced pre-exposure to the conditioned stimulus before its pairing with the unconditioned stimulus during the conditioning stage. LI has been considered as a relevant animal model for the study of the biological bases of schizophrenia. LI has recently been demonstrated to depend on the integrity of the entorhinal cortex, as lesioning of this area disrupted LI. Objectives: The present study aimed to verify whether the classical neuroleptic haloperidol and/or the atypical antipsychotic olanzapine would prevent the effect of entorhinal cortex lesioning. Methods: LI was studied in an off-baseline conditioned emotional response (CER) paradigm in which a tone is paired with a footshock. Entorhinal cortex lesions were produced by the electrolytic method. After a recovery period, both lesioned and control rats received either haloperidol (0.3 mg/kg), olanzapine (0.3 mg/kg) or vehicle before both the pre-exposure and conditioning stages of the experiment. Results: In control rats, pre-exposure to the tone induced LI, which was affected by neither haloperidol nor olanzapine. Lesioning of the entorhinal cortex produced a deficit of LI, which was restored by olanzapine but not by haloperidol. Conclusions: This result suggests a dissociation of the anatomical and pharmacological targets of the two drugs. The possible involvement of dopamine D3 receptors in the effects of olanzapine is discussed. [ABSTRACT FROM AUTHOR]

Aims. We aim to explore the variable photometric and stellar properties of four yellow hypergiants (YHGs), HR 8752, HR 5171A, ρ Cas, and HD 179821, and their pulsations of hundreds of days, and long-term variations (LTVs) of years. We also aim to explore light and colour curves for characteristics betraying evolutionary loops and eruptive episodes and to investigate trends of quasi-periods and the possible need for distance revisions. Methods. We tackled multi-colour and visual photometric data sets, looked for photometric indications betraying eruptions or enhanced mass-loss episodes, calculated stellar properties mainly using a previously published temperature calibration, and investigated the nature of LTVs and their influence on quasi-periods and stellar properties. Results. Based on driven one-zone stellar oscillation models, the pulsations can be characterised as "weakly chaotic". The BV photometry revealed a high-opacity layer in the atmospheres. When the temperature rises the mass loss increases as well, consequently, as the density of the high-opacity layer. As a result, the absorption in B and V grow. The absorption in B, presumably of the order of one to a few 0.m 1 0. m 1 $ 0{{\overset{\text{ m}}{.}}}1 $ , is always higher than in V. This difference renders redder and variable (B − V) colour indexes, but the absorption law is unknown. This property of YHGs is unpredictable and explains why spectroscopic temperatures (reddening independent) are always higher than photometric ones, but the difference decreases with the temperature. A new (weak) eruption of ρ Cas has been identified. We propose shorter distances for ρ Cas and HR 5171A than the accepted ones. Therefore, a correction to decrease the blue luminescence of HR 5171A by polycyclic aromatic hydrocarbon (PAH) molecules is necessary, and HR 5171A would no longer be a member of the cluster Gum48d. HR 5171A is only subject to one source of light variation, not by two as the literature suggests. Eruptive episodes (lasting one to two years), of YHGs prefer relatively cool circumstances when a red evolutionary loop (RL) has shifted the star to the red on the HR diagram. After the eruption, a blue loop evolution (BL) is triggered lasting one to a few decades. We claim that in addition to HR 8752, also the other three YHGs have shown similar cycles over the last 70 years. This supports the suspicion that HD 179821 might be a YHG (with a possible eruptive episode between 1925 and 1960). The range in temperature of these cyclic Teff variations is 3000 K–4000 K. LTVs mainly consist of such BL and RL evolutions, which are responsible for a decrease and increase, respectively, of the quasi-periods. The reddening episode of HR 5171A between 1960 and 1974 was most likely due to a red loop evolution, and the reddening after the 1975 eruption was likely due to a shell ejection, taking place simultaneously with a blue loop evolution. [ABSTRACT FROM AUTHOR]

Summary: Behçet's syndrome (BS) is a complex disease with different organ involvement. The vascular one is the most intriguing, considering the existence of a specific group of patients suffering from recurrent vascular events involving the venous and, more rarely, the arterial vessels. Several clinical clues suggest the inflammatory nature of thrombosis in BS, especially of the venous involvement, thus BS is considered a model of inflammation‐induced thrombosis. Unique among other inflammatory conditions, venous involvement (together with the arterial one) is currently treated with immunosuppressants, rather than with anti‐coagulants. Although many in‐vitro studies have suggested the different roles of the multiple players involved in clot formation, in‐vivo models are crucial to study this process in a physiological context. At present, no clear mechanisms describing the pathophysiology of thrombo‐inflammation in BS exist. Recently, we focused our attention on BS patients as a human in‐vivo model of inflammation‐induced thrombosis to investigate a new mechanism of clot formation. Indeed, fibrinogen displays a critical role not only in inflammatory processes, but also in clot formation, both in the fibrin network and in platelet aggregation. Reactive oxygen species (ROS)‐derived modifications represent the main post‐translational fibrinogen alterations responsible for structural and functional changes. Recent data have revealed that neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. Altogether, these new findings may help understand the pathogenetic bases of inflammation‐induced thrombosis and, more importantly, may suggest potential targets for innovative therapeutic approaches. Thrombotic events in BS are sustained by an inflammatory process rather than a thrombophilic state. Reactive oxygen species (ROS)‐derived modifications represent the main post‐translational fibrinogen alterations responsible for structural and functional changes. Neutrophils (pivotal in the pathogenetic mechanisms leading to BS damage) promote fibrinogen oxidation and thrombus formation in BS. [ABSTRACT FROM AUTHOR]

Aims: To characterize airborne virus‐like particles isolated from two cheese production plants in order to reveal their complexity in terms of viral communities and microbial genes potentially mobilized by viruses. Methods and Results: Airborne virus‐like particles have been isolated from Grana Padano and Gorgonzola PDO cheese production plants and ripening cellars. A shotgun metagenomics analysis of the isolated viromes highlighted a high complexity of the viral communities both in terms of viral taxonomy and phage–host associations. Bacterial reads in each of the viromes were confirmed to be abundant and their taxonomy appeared to be associated with the environmental parameters and the technological processes that characterize the sampling area. Antibiotic resistance genes have been identified in each virome thus confirming that phages could be involved in the mobilization of antimicrobial resistances among bacterial populations. Interestingly human viruses were also identified even if the contamination source was not revealed. Conclusions: The environmental conditions, which are imposed by the technology of the dairy process, seam to shape the viral populations as a consequence of the adaptation of microbial taxa to those environments. The identification of sequences belonging to Legionella pneumophila and to the human papillomavirus, raised some considerations about the safety of cheese‐ripening cellars. Significance and Impact of the study: In conclusion, the analysis of the dairy airborne viromes, has revealed a high complexity of the viral communities even if the environments where the samples were collected were confined environments. Metagenomics of airborne viral population could be a promising monitoring tool for the biological characterization of dairy environments. [ABSTRACT FROM AUTHOR]

Purpose: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study.Methods: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value.Results: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10− 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10− 3 mm2/s) group (p < 2.2 × 10− 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10− 3 mm2/s.Conclusions: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID) is a major health problem in our society. Genetic causes of ID remain unknown because of its vast heterogeneity. Here we report two Finnish families and one Dutch family with affected individuals presenting with mild to moderate ID, neuropsychiatric symptoms and delayed speech development. By utilizing whole exome sequencing (WES), we identified a founder missense variant c. 983T>C (p. Leu328Pro) in seven affected individuals from two Finnish consanguineous families and a deletion c.799_1034- 429delinsTTATGA (p.Gln267fs) in one affected individual from a consanguineous Dutch family in the C12orf4 gene on chromosome 12. Both the variants co-segregated in the respective families as an autosomal recessive trait. Screening of the p. Leu328Pro variant showed enrichment in the North Eastern sub-isolate of Finland among anonymous local blood donors with a carrier frequency of 1:53, similar to other disease mutations with a founder effect in that region. To date, only one Arab family with a three affected individuals with a frameshift insertion variant in C12orf4 has been reported. In summary, we expand and establish the clinical and mutational spectrum of C12orf4 variants. Our findings implicate C12orf4 as a causative gene for autosomal recessive ID. [ABSTRACT FROM AUTHOR]

Abstract: There is a growing interest in identifying biomacromolecules such as proteins and peptides to functionalize metallic surfaces through noncovalent binding. One method for functionalizing materials without fundamentally changing their inherent structure is using biorecognition moieties. Here, we proved a general route to select a biomolecule adhesive motif for surface functionalization by comprehensively screening phage displayed peptides. In particular, we selected a genetically engineered M13 bacteriophage and a linear dodecapeptide derived from its pIII domain for recognizing gold surfaces in a specific and selective manner. In the phage context, we demonstrated the adhesive motif was capable to adsorb on gold in a preferential way with a morphological and viscoelastic signature of the adsorbed layer as evidenced by QCM-D and AFM investigations. Out of the phage context, the linear dodecapeptide is reproducibly found to adhere to the gold surface, and by quantitative SPR measurements, high affinity constants (K eq∼ 106M−1, binding energy ∼−8kcal/mol) were determined. We proved that the interactions occurring at gold interface were mainly hydrophobic as a consequence of high frequency of hydrophobic residues in the peptide sequence. Moreover, by CD, molecular dynamics and steered molecular dynamics, we demonstrated that the molecular flexibility only played a minor role in the peptide adsorption. Such noncovalent but specific modification of inorganic surfaces through high affinity biomolecule adsorption represents a general strategy to modulate the functionality of multipurpose metallic surfaces. [Copyright &y& Elsevier]

The frequency of diurnal clenching and/or grinding and nail-biting habits was assessed in patients affected by temporomandibular disorders (TMDs) and in healthy controls in order to investigate the possible association between these oral parafunctions and different diagnostic subgroups of TMDs. The case group included 557 patients (127 men, mean age ± SD = 34·5 ± 15·4 years; 430 women, mean age ± SD = 32·9 ± 14·1 years) affected by myofascial pain or disc displacement or arthralgia/arthritis/arthrosis. The control group included 111 healthy subjects (55 men, mean age ± SD = 37 ± 15·2 years; 56 women, mean age ± SD = 38·2 ± 13·8 years). Multinomial logistic regression analysis was used to assess the association between oral parafunctions and TMDs, after adjusting for age and gender. Daytime clenching/grinding was a significant risk factor for myofascial pain (odds ratio (OR) = 4·9, 95% confidence interval (CI): 3·0–7·8) and for disc displacement (OR = 2·5, 95% CI: 1·4–4·3), nail biting was not associated to any of the subgroups investigated. Female gender was a significant risk factor for myofascial pain (OR = 3·8; 95% CI: 2·4–6·1), whereas the risk factor for developing disc displacement decreased with ageing. No association was found between gender, age and arthralgia/arthritis/arthrosis. [ABSTRACT FROM AUTHOR]

Latent inhibition (LI), that is the decrease in conditioned response induced by the repeated nonreinforced pre-exposures to the to-be-conditioned stimulus, is disrupted by entorhinal cortex (EC) lesions. The mechanism involved in this disruption is unknown, and in particular the experimental stage (pre-exposure or conditioning) at which the integrity of EC is necessary has to be determined. The purpose of this study was to address this issue by using reversible inactivation of the EC by local micro-infusion of tetrodotoxin (TTX). TTX was infused either before the pre-exposure phase, before the conditioning phase, or before both phases. LI was unaffected in rats that received TTX before conditioning or before both pre-exposure and conditioning. In contrast, LI was disrupted in rats that received TTX before pre-exposure only. These results are discussed in the framework of LI models. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: UN1 is a membrane glycoprotein that is expressed in immature human thymocytes, a subpopulation of peripheral T lymphocytes, the HPB acute lymphoblastic leukemia (ALL) T-cell line and fetal thymus. We previously reported the isolation of a monoclonal antibody (UN1 mAb) recognizing the UN1 protein that was classified as “unclustered” at the 5th and 6th International Workshop and Conference on Human Leukocyte Differentiation Antigens. UN1 was highly expressed in breast cancer tissues and was undetected in non-proliferative lesions and in normal breast tissues, indicating a role for UN1 in the development of a tumorigenic phenotype of breast cancer cells. In this study, we report a partial purification of the UN1 protein from HPB-ALL T cells by anion-exchange chromatography followed by immunoprecipitation with the UN1 mAb and MALDI-TOF MS analysis. This analysis should assist in identifying the amino acid sequence of UN1. [Copyright &y& Elsevier]

Background: The safety and tolerability of sublingual immunotherapy (SLIT) has been documented in allergic patients both in the build-up phase as well as during maintenance, but only two studies have evaluated the occurrence of adverse reactions with an ultra-rush regimen of SLIT induction in a mixed paediatric/adult population. Moreover one of these two studies used a chemically modified extract (allergoid). The aim of the present study was to evaluate the occurrence of immediate or late adverse reactions in allergic children after a very fast (40 min) ultra-rush SLIT induction with two different allergen extract solutions. Methods: We studied 100 children (64 boys, mean age of 9.6 years, range 3.5–16.8), with a history of intermittent/persistent rhinitis and/or intermittent/mild persistent asthma due to inhalant allergens. The ultra-rush build-up phase involved the administration, every 10 min, of increasing doses of the highest-concentration vial of SLIT of two different manufacturers (Anallergo and Stallergènes). Results: All patients completed the treatment, side-effects have been recorded in 19% of the cases: 10% within 1 h after the build-up phase, 7% within 48 h and 2% mixed. A major difference (p = 0.0001) was recorded between Anallergo (6 patients, 8.7%) and Staloral (13 patients, 41.9%), but all the reactions were mild: principally oral symptoms, in 1 case rhinorrhoea and cough, and delayed abdominal pain and diarrhoea in another patient. Conclusions: No severe adverse reactions were observed with this ultra-rush SLIT induction also in the paediatric age; statistical differences have been documented between the two different extracts. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Lesions of the entorhinal cortex are now an accepted model for mimicking some of the neuropathological aspects of schizophrenia, since evidence has accumulated for the presence of cytoarchitectonic abnormalities within this cortex in schizophrenic patients. The present study was undertaken to address the functional consequences of bilateral entorhinal cortex lesions on antipsychotic-induced c-fos expression. After a 15-day recovery period, the effect of a typical antipsychotic, haloperidol (1 mg/kg), on c-fos mRNA expression was compared with that of an atypical one, olanzapine (10 mg/kg), in both sham-lesioned and entorhinal cortex-lesioned rats. In sham-lesioned rats, both haloperidol and olanzapine induced c-fos expression in the caudal cingulate cortex, dorsomedial and dorsolateral caudate-putamen, nucleus accumbens core and shell and lateral septum. In addition, olanzapine, but not haloperidol, increased c-fos expression within the central amygdala. In entorhinal cortex-lesioned rats, haloperidol-induced c-fos expression was markedly reduced in most areas. In contrast, the olanzapine-induced c-fos expression was not altered in the nucleus accumbens shell and lateral septum of the lesioned rats. These findings reveal that entorhinal cortex lesions affect c-fos expression in a compound- and regional-dependent manner. Our results further emphasize the importance of the exploration of the mechanisms of action of antipsychotic drugs in the context of an associated cortical pathology. [Copyright &y& Elsevier]

A letter to the editor is presented regarding distinguishing Bruton's tyrosine kinase (Btk) complex induced by oxidative stress.