Priming effect in children with Type 1 Diabetes Mellitus.

Previous studies have evidenced cognitive difficulties across various domains in Type 1 Diabetes Mellitus (T1DM) children, but the implicit memory system has not yet been systematically explored.Taking into account that the interplay between memory and perception may be modulated by the semantic category of the stimuli and their salience, we explored explicit and implicit memory using both object and food stimuli to verify whether for T1DM children there is a feebleness in performing the function of memory as a function of the stimuli used.Eighteen T1DM children and 47 healthy children performed an explicit recognition task in which they were requested to judge whether the presented image had already been shown ("old") or not ("new") and an identification priming task in which they were asked to name new and old pictures presented at nine ascending levels of spatial filtering.Results did not reveal any differences between controls and T1DM children in the explicit memory recognition task, whereas some differences between the two groups were found in the identification priming task. In T1DM children, the priming effect was observed only for food images.The dissociation between implicit and explicit memory observed in children with diabetes seems to be modulated by the category of the stimuli, and these results underscore the relevance of taking into account this variable when exploring cognitive functions.

Automatic and controlled attentional orienting in the elderly: A dual-process view of the positivity effect.

The positivity effect in the elderly consists of an attentional preference for positive information as well as avoidance of negative information. Extant theories predict either that the positivity effect depends on controlled attentional processes (socio-emotional selectivity theory), or on an automatic gating selection mechanism (dynamic integration theory). This study examined the role of automatic and controlled attention in the positivity effect. Two dot-probe tasks (with the duration of the stimuli lasting 100 ms and 500 ms, respectively) were employed to compare the attentional bias of 35 elderly people to that of 35 young adults. The stimuli used were expressive faces displaying neutral, disgusted, fearful, and happy expressions. In comparison to young people, the elderly allocated more attention to happy faces at 100 ms and they tended to avoid fearful faces at 500 ms. The findings are not predicted by either theory taken alone, but support the hypothesis that the positivity effect in the elderly is driven by two different processes: an automatic attention bias toward positive stimuli, and a controlled mechanism that diverts attention away from negative stimuli.

Electrophysiological Activity Prior to Self-initiated Movements is Related to Impulsive Personality Traits.

Electrophysiological and neuroimaging studies suggest that our actions are initiated by unconscious mental processes long before awareness of intention to act. The time window between the awareness of the intention to move and the movement onset, which normally permits to exert a conscious "veto" on the impending action, is modulated by individual differences in trait impulsivity. In particular, trait impulsive people show a delayed awareness of the intention to act, probably exceeding the "point of no return", after which the action can no longer be inhibited. In order to investigate if individual differences in the "veto" interval might be explained by differences in the readiness potential (RP) dynamics, nineteen healthy participants underwent an impulsivity trait assessment using the Barratt Impulsiveness Scale (BIS-11) and performed a task based on Libet's clock paradigm, during EEG recordings of pre-movement neural activity. We observed a positive relationship between impulsive personality trait and motor system excitability during the preparation of self-initiated movements. In particular, the RP showed an earlier negative rising phase and a greater amplitude, with the increasing of BIS-11 scores. Based on present results, we conclude hypothesizing that trait impulsivity might be characterized by less effective preparatory inhibition mechanisms, which have a fundamental role in the control of behavior.

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

BACKGROUND: In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. METHODS: 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. KEY RESULTS: Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). CONCLUSIONS & INFERENCES: The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity.

Relationship between impulsivity traits and awareness of motor intention.

Deficient voluntary control of behaviour and impulsivity are key aspects of impulse control disorders. The objective of the present study was to evaluate the relationship between behavioural measures of impulsivity and the awareness of voluntary action. Seventy-four healthy volunteers completed the Barratt Impulsiveness Scale (BIS), a questionnaire used to measure impulsive personality traits, and a go/no-go task. Moreover, all participants performed a behavioural task based on the Libet's clock paradigm in which they were requested to report the time of a self-initiated movement (M-judgement) or the time they first feel their intention to move (W-judgement). A positive relationship between the time in which subjects reported the intention to move (W-judgement) and impulsivity measures emerged. Namely, the higher was the score in the attentional and motor impulsivity subscales of the BIS and the number of inhibitory failure responses in the go/no-go task, the lower was the difference between the W-judgement and the actual movement (i.e. the awareness of intention to move was closer to the voluntary movement execution). In contrast, no relationship emerged with M-judgement. The present findings suggest that impulsivity is related to a delayed awareness of voluntary action. We hypothesize that in impulse control disorders, the short interval between conscious intention and actual movement may interfere with processes underlying the conscious 'veto' of the impending action.

Audio-visual integration effect in lateral occipital cortex during an object recognition task: An interference pilot study.

BACKGROUND: Recent neuroimaging data support the hypothesis of a multisensory interplay at low-level sensory-specific cortex. OBJECTIVE: We used an on-line interference approach by rTMS to investigate the role of the left lateral occipital cortex (LOC) in audio-visual (AV) object recognition process. METHODS: Fifteen healthy volunteers performed a visual identification task of degraded pictures presented alone or simultaneously to coherent or non-coherent sounds. Focal 10-Hz rTMS at an intensity of 100% resting motor threshold was delivered simultaneously to the picture. Two blocks of 60 pictures were randomly displayed in two different experimental conditions: rTMS of the left LOC and over Cz. RESULTS: rTMS of the left LOC produced a worsening of the accuracy compared to rTMS over Cz specifically in the coherent AV condition. CONCLUSION: These data support the view that audio-visual interaction effect may occur at early stage of recognition processing.

Prevalence of Fasciola hepatica in Galba truncatula detected by Multiplex PCR in the province of El Tarf (Algeria).

The prevalence of Fasciola hepatica infection in the snail Galba truncatula was studied for the first time in Algeria using Multiplex PCR. A total of 722 individuals were collected from 11 typical habitats (temporary ponds, road ditches and puddles) distributed in five localities of the El Tarf province, known for endemicity of fascioliasis. Snails were divided in 75 groups and DNA extraction was performed using Chelex® (Biorad, Nazareth Eke). Two primers were used, the first is specific for 124 bp DNA fragment of Fasciola sp and the second one represents the ITS-2 lymnaeids sequence (500-600 bp). The prevalence of the infection was estimated to be 46.66% for pools (35/75 were positive). The bursting out of the pools show that 75 snails were carriers of F. hepatica which gives an overall infection rate of about 10.74%. The results of snails infection according to their sizes showed significant differences in the studied size classes, thus snails of big sizes were the most infected. Based on these data, epidemiological implication of Multiplex PCR as a fully reliable technique to highlight high risks periods of fasciolosis will be of a great interest.

Prevalence of Fasciola hepatica in Galba truncatula detected by Multiplex PCR in the province of El Tarf (Algeria)

The prevalence of Fasciola hepatica infection in the snail Galba truncatula was studied for the first time in Algeria using Multiplex PCR. A total of 722 individuals were collected from 11 typical habitats (temporary ponds, road ditches and puddles) distributed in five localities of the El Tarf province, known for endemicity of fascioliasis. Snails were divided in 75 groups and DNA extraction was performed using Chelex® (Biorad, Nazareth Eke). Two primers were used, the first is specific for 124 bp DNA fragment of Fasciola sp and the second one represents the ITS-2 lymnaeids sequence (500–600 bp). The prevalence of the infection was estimated to be 46.66% for pools (35/75 were positive). The bursting out of the pools show that 75 snails were carriers of F. hepatica which gives an overall infection rate of about 10.74%. The results of snails infection according to their sizes showed significant differences in the studied size classes, thus snails of big sizes were the most infected. Based on these data, epidemiological implication of Multiplex PCR as a fully reliable technique to highlight high risks periods of fasciolosis will be of a great interest.

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified.

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK-. Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK- and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK-, respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated.

Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), whereas functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivation of BPDCN that proved to originate from the myeloid lineage and in particular, from resting pDCs. Furthermore, thanks to an integrated bioinformatic approach we discovered aberrant activation of the NF-kB pathway and suggested it as a novel therapeutic target. We tested the efficacy of anti-NF-kB-treatment on the BPDCN cell line CAL-1, and successfully demonstrated by GEP and IHC the molecular shutoff of the NF-kB pathway. In conclusion, we identified a molecular signature representative of the transcriptional abnormalities of BPDCN and developed a cellular model proposing a novel therapeutic approach in the setting of this otherwise incurable disease.

Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.

Peripheral T-cell lymphomas not otherwise specified (PTCL/NOS) are very aggressive tumors characterized by consistent aberrant expression of platelet-derived growth factor receptor alpha (PDGFRA). In this study, we aimed to identify the determinants of PDGFRA activity in PTCL/NOS and to elucidate the biological consequences of its activation. We observed overexpression of the PDGFRA gene by gene expression profiling in most of the tested PTCLs and confirmed the expression of PDGFRA and phospho-PDGFRA using immunohistochemistry. The integrity of the PDFGRA locus was demonstrated using several different approaches, including massive parallel sequencing and Sanger sequencing. PDGF-AA was found to be expressed and secreted by PTCL/NOS cells and to be necessary and sufficient for PDGFRA phosphorylation ex vivo by sustaining an autocrine stimulation. We documented consistently high PDGF-A expression in primary biopsies and patients' plasma and tracked PDGFRA signaling in primary tumors, achieving evidence of its activation. Indeed, we found that STAT1 and STAT5 are implicated in PDGFRA signaling transduction. Finally, we demonstrated that PDGFRA activation supported tumor cell proliferation and provided the first evidence of the anti-lymphoma activity of PDGRA inhibition in a PTCL/NOS patient. Altogether, our data demonstrated that PDGFRA activity fosters PTCL/NOS proliferation via an autocrine loop.

Fearful expressions enhance recognition memory: electrophysiological evidence.

Facial expressions play a key role in affective and social behavior. However, the temporal dynamics of the brain responses to emotional faces remain still unclear, in particular an open question is at what stage of face processing expressions might influence encoding and recognition memory. To try and answer this question we recorded the event-related potentials (ERPs) elicited in an old/new recognition task. A novel aspect of the present design was that whereas faces were presented during the study phase with either a happy, fearful or neutral expression, they were always neutral during the memory retrieval task. The ERP results showed three main findings: An enhanced early fronto-central positivity for faces encoded as fearful, both during the study and the retrieval phase. During encoding subsequent memory (Dm effect) was influenced by emotion. At retrieval the early components P100 and N170 were modulated by the emotional expression of the face at the encoding phase. Finally, the later ERP components related to recognition memory were modulated by the previously encoded facial expressions. Overall, these results suggest that face recognition is modulated by top-down influences from brain areas associated with emotional memory, enhancing encoding and retrieval in particular for fearful emotional expressions.

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays.

To better define the significance of proliferation centers (PCs), the morphological hallmark of chronic lymphocytic leukemia (CLL), lymph node biopsies taken from 183 patients were submitted to histopathologic and fluorescence in situ hybridization (FISH) studies using a 5-probe panel on tissue microarrays. Seventy-five cases (40.9%) with confluent PCs were classified as 'PCs-rich' and 108 cases (59.1%) with scattered PCs were classified as 'typical'. Complete FISH data were obtained in 101 cases (55.1%), 79 of which (78.2%) displayed at least one chromosomal aberration. The incidence of each aberration was: 13q- 36,7%, 14q32 translocations 30.8%, 11q- 24.7%, trisomy 12 19.5% and 17p- 15.6%. Five cases showed extra copies of the 14q32 region. The 'PCs-rich' group was associated with 17p-, 14q32/IgH translocation, +12, Ki-67>30%. The median survival from the time of tissue biopsy for PCs-rich and typical groups was 11 and 64 months, respectively (P=0.00001). The PCs-rich pattern was the only predictive factor of an inferior survival at multivariate analysis (P=0.022). These findings establish an association between cytogenetic profile and the amount of PC in CLL, and show that this histopathologic characteristic is of value for risk assessment in patients with clinically significant adenopathy.

ARFI elastography in patients with chronic autoimmune liver diseases: A preliminary study.

OBJECTIVE: Acoustic radiation force impulse (ARFI) is a new software-based technique that evaluates liver stiffness during B-mode ultrasonography. The purpose of this study was to evaluate the accuracy of ARFI in distinguishing patients with chronic autoimmune liver disease from healthy subjects. MATERIAL AND METHODS: We enrolled 9 adult patients (8 women, 1 man; age 48.1 ± 12.8 years) with chronic autoimmune disease (primary biliary cirrhosis (PBC, n = 3), autoimmune hepatitis (AIH, n = 2), primary sclerosing cholangitis (PSC, n = 1) and overlap syndromes, (n = 3) who underwent a liver biopsy and 11 healthy volunteers (age 34.7 ± 10.4 years; 7 women, 4 men). Liver stiffness was evaluated and expressed as the shear wave velocity (SWV) in m/sec. We used a US scanner Siemens-Acuson S2000, evaluating the right liver lobe and the left liver lobe. RESULTS: THE SWV WAS SIGNIFICANTLY HIGHER IN CASES (RIGHT LOBE: 1.51 ± 0.44; left lobe: 1.57 ± 0.40) than in controls (right lobe: 1.08 ± 0.10; left lobe: 1.12 ± 0.13) (right lobe: P = 0.002; left lobe: P = 0.013). We found no significant correlation between right and left lobe SWVs in cases (P = 0.779) or controls (P = 0.385). The SWV cut-off that best distinguished cases from controls was 1.25 m/sec (accuracy: AUC=0.885; sensitivity: 70.6%; specificity: 95.5%). CONCLUSIONS: ARFI elastography is a noninvasive ultrasonographic technique that can differentiate healthy subjects from patients with fibrotic stages of chronic liver disease.

Real-time elastography as a noninvasive technique for quantification of fibrosis in patients with chronic viral liver disease: Preliminary findings.

INTRODUCTION: Real-time elastography (RTE) is a novel technique for measuring tissue elasticity. The aims of this study were to prospectively measure liver stiffness with RTE in patients with chronic viral hepatitis and to evaluate the possible correlation between RTE data and the extent of fibrosis based on liver biopsy findings (Ishak score). MATERIAL AND METHODS: Between February and October 2011, 26 patients (18M, 8F, mean age 41 ± 13 [standard deviation], range 22-62) with chronic viral hepatitis were prospectively evaluated with ultrasonography (US) that included RTE. All patients then underwent US-guided percutaneous liver biopsy (right lobe) for evaluation of fibrosis. Examinations were performed with a iU22 scanner (Philips, Bothell, WA, USA); a convex transducer (C5-1) was used for the US examination, and a linear transducer (L12-5) for RTE. In the RTE images, relative tissue stiffness is expressed according to a color scale with soft areas represented in green/red and hard areas in blue. Patients were examined in the supine position in suspended normal respiration; three loops of 20 RTE frames were recorded for each case. For each patient, we calculated the mean strain ratio (MSR) for the 3 loops. The Spearman correlation coefficient was used to assess correlation between the ASR and fibrosis stage (F) reflected by the Ishak score. RESULTS: The Spearman coefficient showed significant correlation between the MSR and F (Rho = 0.470, p = 0.015). CONCLUSIONS: RTE appears to be a useful tool for noninvasive evaluation of fibrosis in patients with chronic viral hepatitis although these findings need to be confirmed in larger case series.

An optimized DNA extraction and multiplex PCR for the detection of Fasciola sp. in lymnaeid snails.

This study deals with the development and validation of an original PCR protocol to assess the presence of Fasciola hepatica in Galba truncatula its main intermediate host in Western Europe. In the present study two DNA extraction techniques are compared and a new multiplex PCR is described. The Chelex(®) DNA extraction technique showed to be more appropriate than the classical Phenol/Chloroform/Proteinase K based method because of the absence of toxic organic solvent, shorter duration and lower cost, and a higher reproducibility regarding DNA concentrations and wavelength ratios. The multiplex PCR was set up to amplify the lymnaeid internal transcribed spacer 2 sequence (500-600 bp) that act as an internal control and a 124 bp Fasciola sp. sequence that is repeated more than 300,000 times in fluke whole genome. Ninety six snails were pooled and 6 snails (6.25%) found positive for Fasciola sp. The limit of detection is lower than the minimal biological infestation unit (one miracidium). DNA extracts from Paramphistomum daubneyi, Dicrocoelium lanceolatum, and Fascioloides magna did not cross react.

Natural radioactivity in refractory manufacturing plants and exposure of workers to ionising radiation.

This paper shows the results of a survey carried out at some refractory manufacturing plants. During the first part of the survey, the concentration of natural radioactivity in raw materials and end-products, coming from four plants, was assessed. Several raw materials and, as a consequence, some end-products as well have shown activity concentrations exceeding a few hundreds of Bq kg(-1) of (238)U and (232)Th. In some important raw materials, such as bauxite and corundums, a remarkable radioactive disequilibrium was observed; this is probably due to the high temperature processes undergone by these materials. The second part of the survey focussed on the measurements of ambient equivalent dose rates, airborne dust concentrations and radon indoor. On the basis of results obtained, the effective dose for the standard worker was estimated. Two different types of refractory plants were investigated. Effective doses for both plants were lower than 1 mSv y(-1).

Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies.

Peripheral T cell lymphomas (PTCL) account for about 12% of lymphoid tumours worldwide. Almost half show such morphological and molecular variability as to hamper any further classification, and to justify their inclusion in a waste-basket category termed "not otherwise specified (NOS)". The latter term is used for neoplasms with aggressive presentation, poor response to therapy and dismal prognosis. In contrast to B cell lymphomas, PTCL have been the subject of only a limited number of studies to elucidate their pathobiology and identify novel pharmacological approaches. Herewith, the authors revise the most recent contributions on the subject based on the experience they have gained in the extensive application of microarray technologies. PTCL/NOS are characterised by erratic expression of T cell associated antigens, including CD4 and CD52, which have recently been proposed as targets for ad hoc immunotherapies. PTCL/NOS also show variable Ki-67 marking, with rates >80% heralding a worse prognosis. Gene expression profiling studies have revealed that PTCL/NOS derive from activated T lymphocytes, more often of the CD4+ type, and bear a signature composed of 155 genes and related products that play a pivotal role in cell signalling transduction, proliferation, apoptosis and matrix remodelling. This observation seems to pave the way for the use of innovative drugs such as tyrosine kinase and histone deacetylase inhibitors whose efficacy has been proven in PTCL primary cell cultures. Gene expression profiling also allows better distinction of PTCL/NOS from angioimmunoblastic T cell lymphoma, the latter being characterised by follicular T helper lymphocyte derivation and CXCL13, PD1 and vascular endothelial growth factor expression.

Recognition of category-related visual stimuli in Parkinson's disease: before and after pharmacological treatment.

Visual-sensory dysfunctions and semantic processing impairments are widely reported in Parkinson's disease (PD) research. The present study investigated the category-specific deficit in object recognition as a function of both the semantic category and spatial frequency content of stimuli. In the first experiment, the role of dopamine in object-recognition processing was assessed by comparing PD drug naïve (PD-DN), PD receiving levodopa treatment (PD-LD), and control subjects. Experiment 2 consisted of a retest session for PD drug naïve subjects after a period of pharmacological treatment. All participants completed an identification task which displayed animals and tools at nine levels of filtering. Each object was revealed in a sequence of frames whereby the object was presented at increasingly less-filtered images up to a complete version of the image. Results indicate an impaired identification pattern for PD-DN subjects solely for animal category stimuli. This differential pharmacological therapy effect was also confirmed at retest (experiment 2). Thus, our data suggest that dopaminergic loss has a specific role in category-specific impairment. Two possible hypotheses are discussed that may account for the defective recognition of semantically different objects in PD.