Defective FoxP3+ Treg cell differentiation in the gut of Type 1 Diabetic patients

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in the gut and is crucial to maintain systemic immune tolerance, is impaired in T1D patients. These results provide the first evidence that gut mucosa alteration could predispose to autoimmune T1D by affecting systemic immune regulation

On the Need of Intermediate Complexity General Circulation Models: A "SPEEDY" Example

processes that allows realistic and fast climate simula -tions that often involve large ensembles for the purpose of reducing uncertainty and estimation of the forced and internal variability of the system. The forced signal is typically estimated by an ensemble mean of many simulations, but ensembles of state-of-the-art models are often too small to reduce the remaining internal variability. The ensemble size needed to estimate the mean accurately depends on the signal-to-noise ratio for the variable and region under consideration. For example, the ensemble size to estimate midlatitude 500-hPa height accurately is about 20, which is larger than most ensembles used in seasonal hindcast data-sets or climate projections performed by individual centers. Intermediate complexity models can also be used efficiently to investigate the sensitivity of simu-lated climate to changes in parameters in the physical parameterizations. Another application is related to climate change. For example, Forest et al. (2002) and Sokolov at al. (2009) use the MIT Integrated Global System Model (MIT IGSM) to investigate topics such as climate sensitivity, aerosol forcing, ocean heat uptake rate, and probabilistic projections of climate change. There are many intermediate complexity system models of intermediate complexity (EMICs). A number of them are participating in the IPCC Fifth Assessment Report and can be found at http://climate .uvic.ca/EMICAR5 (one of which is based on a previous version of the model introduced here). This website also provides information about experiments that are performed with these models that range from en-sembles of 1,000-year-long historical simulations to the assessment of different C

COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10–14

The functional Val158Met COMT polymorphism appears to affect a host of behaviours mediated by the pre-frontal cortex, and has been found associated to the risk for disruptive behaviours including ADHD. Parental socioeconomic status (SES) has also been reported as a predictor for the same childhood disorders. In a general population sample of 575 Italian pre-adolescents aged 10–14, we examined the association of the functional Val158Met COMT polymorphism and SES—both as linear and interactive effects—with oppositional defiant problems, conduct problems, and attention deficit/hyperactivity problems, as defined by the newly established Child Behaviour Check-List/6-18 DSM oriented scales. Multivariate- and subsequent univariate-analysis of covariance showed a significant association of COMT × SES interaction with CBCL 6/18 DOS attention deficit/hyperactivity problems (p = 0.004), and revealed higher scores among those children with Val/Val COMT genotype who belonged to low-SES families. We also found a significant association of SES with attention deficit/hyperactivity problems and conduct problems DOS (p = 0.04 and 0.01, respectively). Our data are consistent with a bulk of recent literature suggesting a role of environmental factors in moderating the contribution of specific genetic polymorphisms to human variability in ADHD. While future investigations will refine and better clarify which specific environmental and genetic mechanisms are at work in influencing the individual risk to ADHD in pre-adolescence, these data may contribute to identify/prevent the risk for ADHD problems in childhood

Clinical Effects of an ACT-Group Training in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Abstract Objective The aim of the present study is evaluate the effectiveness of an Acceptance and Commitment Therapy (ACT)-based training protocol, in adjunct to token economy and previous parent training, in a sample of children with Attention-Deficit/Hyperactivity Disorder (ADHD). By promoting the reduction of immediate responses to thoughts and feelings, we aimed to reduce the impulsive behaviour of children and to improve their self-regulation. Methods The protocol was centred on awareness of the present moment, defusion and acceptance of feelings and emotions. Behavioural (Conners' Parent Rating Scale -Revised: Long version, CPRS-R:L) and severity measures (Clinical Global Impression -Severity, CGI-S) were assessed before and after treatment in a clinical sample of 31 children aged 8–13 years. Results At the end of the ACT protocol, children showed significant improvement in global functioning and behavioural symptoms. There were significant improvements in the CPRS subscales Cognitive Problems (p = 0.005), Hyperactivity (p = 0.006), Perfectionism (p = 0.017), ADHD Index (p = 0.023), Global Index: Restless–Impulsive (p = 0.023), Global Index: Total (p = 0.036), DSM IV Inattentive (p = 0.029), DSM IV Hyperactive–Impulsive (p = 0.016), and DSM IV Total (p = 0.003). When controlling for the confounding effect of pharmacological therapy, comorbidities and socio-economic status, treatment maintained a significant effect on the CPRS subscales Perfectionism (partial η2 = 0.31, p < 0.01), Global Index: Restless–Impulsive (partial η2 = 0.29, p < 0.01), Global Index: Total (partial η2 = 0.31, p < 0.01), DSM IV Hyperactive–Impulsive (partial η2 = 0.20, p = 0.02). Symptom severity as rated by CGI-S scores decreased in 74.2% of the children. Conclusions This preliminary work on an Acceptance and Commitment Therapy-based child training in children affected by ADHD resulted in significant improvements, measured by a rating scale specific for ADHD

Artificial neural network EMG classifier for functional hand grasp movements prediction

To design and implement an electromyography (EMG)-based controller for a hand robotic assistive device, which is able to classify the user's motion intention before the effective kinematic movement execution

Role of mycotoxins in the pathobiology of autism: A first evidence

Objectives: Gene–environment interaction is an emerging hypothesis to expound not only the autism pathogenesis but also the increased incidence of neurodevelopmental disorders (such as autistic spectrum disorder, attention-deficit, hyperactivity disorder). Among xenobiotics, mycotoxins are worldwide contaminants of food that provoke toxicological effects, crucially resembling several symptoms associated with autism such as oxidative stress, intestinal permeability, and inflammation. Here, we focused on a group of mycotoxins to test their role in the manifestation of autism, try to explain their mechanism of action, and discuss possible preventive and therapeutic interventions.Methods: Autistic children (n = 52) and healthy children [n = 58 (31 siblings and 27 unrelated subjects)] were recruited and body fluids and clinical data collected. The diagnosis of autism was made according to DSM V criteria, then with GMDS 0-2, WPPSI, and ADOS. Ochratoxin A (OTA), gliotoxin, zearalenone, and sphingosine/sphinganin..

An Automatic Identification Procedure to Promote the use of FES-Cycling Training for Hemiparetic Patients.

Cycling induced by Functional Electrical Stimulation (FES) training currently requires a manual setting of different parameters, which is a time-consuming and scarcely repeatable procedure. We proposed an automatic procedure for setting session-specific parameters optimized for hemiparetic patients. This procedure consisted of the identification of the stimulation strategy as the angular ranges during which FES drove the motion, the comparison between the identified strategy and the physiological muscular activation strategy, and the setting of the pulse amplitude and duration of each stimulated muscle. Preliminary trials on 10 healthy volunteers helped define the procedure. Feasibility tests on 8 hemiparetic patients (5 stroke, 3 traumatic brain injury) were performed. The procedure maximized the motor output within the tolerance constraint, identified a biomimetic strategy in 6 patients, and always lasted less than 5 minutes. Its reasonable duration and automatic nature make the procedure usable at the beginning of every training session, potentially enhancing the performance of FES-cycling training

The Neural Correlates of Long-Term Carryover following Functional Electrical Stimulation for Stroke

Neurorehabilitation effective delivery for stroke is likely to be improved by establishing a mechanistic understanding of how to enhance adaptive plasticity. Functional electrical stimulation is effective at reducing poststroke foot drop; in some patients, the effect persists after therapy has finished with an unknown mechanism. We used fMRI to examine neural correlates of functional electrical stimulation key elements, volitional intent to move and concurrent stimulation, in a group of chronic stroke patients receiving functional electrical stimulation for foot-drop correction. Patients exhibited task-related activation in a complex network, sharing bilateral sensorimotor and supplementary motor activation with age-matched controls. We observed consistent separation of patients with and without carryover effect on the basis of brain responses. Patients who experienced the carryover effect had responses in supplementary motor area that correspond to healthy controls; the interaction between experimental factors in contralateral angular gyrus was seen only in those without carryover. We suggest that the functional electrical stimulation carryover mechanism of action is based on movement prediction and sense of agency/body ownership-the ability of a patient to plan the movement and to perceive the stimulation as a part of his/her own control loop is important for carryover effect to take place

Comparison of nasopharyngeal nylon flocked swabs with universal transport medium and rayon- bud swabs with a sponge reservoir of viral transport medium in the diagnosis of paediatric influenza

This study compared a kit containing a nasopharyngeal nylon flocked swab and a tube with a liquid universal transport medium (UTM) with a kit containing a plastic-shafted rayon-budded swab with a sponge reservoir of viral transport medium for the molecular detection of influenza viruses in children. Respiratory samples were collected from 314 children aged ,5 years with influenza-like illness (186 males; mean age 2.32±2.27 years) using both swabs in a randomized sequence for each patient. The flocked swabs permitted the detection of 28 influenza A (8.9 %) and 45 influenza B (14.3 %) cases, and the rayon-bud swabs 26 influenza A (8.3 %) and 43 influenza B (13.7 %) cases, with detection rates of 23.2 and 22.0 %, respectively, and similar cycle threshold values. Paediatricians and laboratory staff were significantly more satisfied with both the simplicity (P ,0.0001) and rapidity (P ,0.0001) of the nasopharyngeal flocked swabs with UTM. These findings show that the flocked swabs with UTM and the rayon-bud swabs with a sponge transport medium are similarly efficient in preserving influenza virus nucleic acid, but that the kit containing a flocked swab with a UTM allows easier and more rapid collection and processing of specimens. INTRODUCTION Respiratory infections are the most common diseases of infants and children Antigen detection tests and PCR-based methods are both currently used to detect viruses in respiratory secretions There are various kits containing a nasopharyngeal swab and a tube with transport medium on the market, but only a few studies, mainly of adults, have compared their efficiency in collecting respiratory cells and preserving influenza virus nucleic acid Sample collection. Two samples were collected from each patient and transported by means of two kits: one containing a flexible nasopharyngeal nylon flocked swab and a mini-tube with 1 ml liquid universal transport medium (UTM; Copan Italia), and the other a rayon-budded swab with a tube containing a sponge pre-impregnated with transport medium (Virocult; Medical Wire &amp; Equipment). Using the swabs in a randomized sequence, two nasopharyngeal samples were collected from each child (one from each nostril) by trained paediatricians (L. C., L. G. and S. B.). The distance between the patient&apos;s nares and ear lobe was measured to estimate the length of insertion, after which the swabs were gently inserted towards the pharynx until resistance was felt and then rotated three times to obtain epithelial cells. They were then withdrawn and put into the tube containing the specific transport medium. All of the specimens were kept cool and delivered to the laboratory within 3 h of collection. Sample processing. In the laboratory, each swab was processed in triplicate by three researchers (C. G. M., C. D. and A. V.) as indicated by the manufacturers: 190 ml of the liquid transport medium for the flocked swabs was used directly, whereas the rayon-budded swabs were placed in a tube containing 1 ml liquid lysis buffer (the same amount as that contained in the mini-UTM), the tube was vortexed and incubated for 10 min at room temperature, and 190 ml of the solution was used for extraction. PCR. Viral RNA was extracted from all of the samples by means of a NucliSENS EasyMAG automated extraction system (bioMeriéux), using phocine distemper virus (PDV) as an extraction/PCR inhibition control as described previously (Bosis et al., 2005; Staff satisfaction. Trained paediatricians and members of the laboratory staff were asked to record their satisfaction with the simplicity and rapidity using the swabs after the enrolment of each patient or the completion of the analysis of each pair of swabs by completing a 5-point scale (from 5 &apos;very satisfied&apos; to 1 &apos;very dissatisfied&apos;). Statistical analysis. The data relating to the paired specimens collected from 314 children (186 males, 59.2 %), with a mean age of 2.32±2.27 years, were compared using SAS version 9.1 software (SAS Institute). Continuous variables were analysed using Wilcoxon&apos;s signed rank test or rank sum test as appropriate, and the categorical variables by means of contingency tables and a x 2 or Fisher&apos;s test. RESULTS AND DISCUSSION Satisfaction was based on a 5-point scale from 5 &apos;very satisfied&apos; to 1 &apos;very dissatisfied&apos;. .20 for influenza B virus. However, the paediatricians and laboratory staff were significantly more satisfied with both the simplicity (P ,0.0001) and the rapidity (P ,0.0001) of the nasopharyngeal flocked swabs with UTM. Our study showed that the flocked swabs with UTM and the rayon-budded swabs with transport medium preimpregnated sponge were similarly efficient in preserving influenza virus nucleic acid, but that the former were considered better in terms of the simplicity and rapidity of collection and laboratory testing. Systematic evaluation of the aetiology of paediatric respiratory infections is increasingly being considered an important means of preventing their spread and rationalizing therapy Our main finding was that the paediatricians preferred the flocked swabs because they were more flexible and made it easier and quicker to collect the samples. In addition, the laboratory staff found that the kit containing a flocked swab and liquid transport medium was advantageous insofar as it allowed RNA extraction and PCR to be performed directly on the liquid without the need to add further buffer, whereas the kit containing a transport medium pre-impregnated sponge required an additional step that made the procedure more complicated, timeconsuming and at risk of contamination. One limitation of this study is represented by the fact that the interpretation of the results on simplicity and rapidity of collection and laboratory testing may be devalued by repeated scoring and clustering by the same staff members. This means that further studies that involve several swab collectors and laboratory researchers are required to confirm our results. Moreover, our aim was to compare the efficiency of the two kits in detecting influenza virus nucleic acid, but further studies are required to evaluate the sensitivity of the two transport systems with serial dilutions of positive samples of influenza A and B viruses. Finally, a complete comparison of the sensitivity and specificity of the two kits should also include detection of other respiratory viruses that are commonly found in respiratory samples (e.g. respiratory syncytial virus, adenovirus, rhinovirus), and future research should address this aim. In conclusion, both the flocked swabs with UTM and the rayon-bud swabs with a sponge reservoir of viral transport medium allow adequate collection, transport and preservation of nasal secretions for influenza detection. However, the kit containing a flocked swab with a liquid transport medium facilitated rapid specimen collection and processing. These factors should be considered together with local costs when choosing a product to use in clinical practice. ACKNOWLEDGEMENT