11 research outputs found
oneChannelGUI: a graphical interface to Bioconductor tools, designed for life scientists who are not familiar with R language
No full textOneChannelGUI is an add-on Bioconductor package providing a new set of functions extending the capability of the affylmGUI package. This library provides a graphical interface (GUI) for Bioconductor libraries to be used for quality control, normalization, filtering, statistical validation and data mining for single channel microarrays. Affymetrix 3' expression (IVT) arrays as well as the new whole transcript expression arrays, i.e. gene/exon 1.0 ST, are actually implemented. oneChannelGUI is available for most platforms on which R runs, i.e. Windows and Unix-like machines. © The Author 2007. Published by Oxford University Press. All rights reserved
The UniTrap resource: Tools for the biologist enabling optimized use of gene trap clones
No full textWe have developed a comprehensive resource devoted to biologists wanting to optimize the use of gene trap clones in their experiments. We have processed 300 602 such clones from both public and private projects to generate 28 199 'UniTraps', i.e. distinct collections of unambiguous insertions at the same subgenic region of annotated genes. The UniTrap resource contains data relative to 9583 trapped genes, which represent 42.3% of the mouse gene content. Among the trapped genes, 7 728 have a counterpart in humans, and 677 are known to be involved in the pathogenesis of human diseases. The aim of this analysis is to provide the wet lab researchers with a comprehensive database and curated tools for (i) identifying and comparing the clones carrying a trap into the genes of interest, (ii) evaluating the severity of the mutation to the protein function in each independent trapping event and (iii) supplying complete information to perform PCR, RT-PCR and restriction experiments to verify the clone and identify the exact point of vector insertion. To share this unique resource with the scientific community, we have designed and implemented a web interface that is freely accessible at http://unitrap.cbm.fvg.it/. © 2007 The Author(s)
LONG-TERM HOME-BASED FRONTO-CEREBELLAR TRANSCRANIAL DIRECT CURRENT STIMULATION FOR AUTISM SPECTRUM DISORDER: A CASE SERIES
No full textEmotional reactivity in referred youth with disruptive behavior disorders: the role of the callous-unemotional traits
No full textDeficits in emotional reactivity are frequently reported in Disruptive Behavior Disorders (DBDs). A deficit in
prosocial emotions, namely the callous unemotional traits (CU), may be a mediator of emotional reactivity.
Our aim is to investigate subjective emotional reactivity towards visual stimuli with different affective
valence in youths with DBDs and healthy controls. The clinical sample included 62 youths with DBDs (51
males, 8 to16 years, mean 11.372.1 years), the control group 53subjects (36 males,8 to 16 years, mean
10.871.5 years). The groups were compared using the Child Behavior Checklist (CBCL), the Inventory of
Callous-Unemotional Traits (ICU),and the International Affective Picture System (IAPS),which explores the
affective(pleasant/unpleasant emotional reaction) and arousal (low/high intensity of emotion) dimen-
sions.The DBD group presented higher scores in externalizing and internalizing CBCL scores, and in ICU
callous and indifferent subscales. At the IAPS,DBD patients differed from controls in the affective valence
of the images, rating less unpleasant neutral and negative images. The CU traits were the only predictor of
emotional reactivity in the DBD sample. A less aversive way to interpret neutral and negatives timuli may
explain why DBD patients are less responsive to negative reinforcements
The combination of transcriptomics and informatics identifies pathways targeted by miR-204 during neurogenesis and axon guidance
No full textVertebrate organogenesis is critically sensitive to gene dosage and even subtle variations in the expression levels of key genes may result in a variety of tissue anomalies. MicroRNAs (miRNAs) are fundamental regulators of gene expression and their role in vertebrate tissue patterning is just beginning to be elucidated. To gain further insight into this issue, we analysed the transcriptomic consequences of manipulating the expression of miR-204 in the Medaka fish model system. We used RNA-Seq and an innovative bioinformatics approach, which combines conventional differential expression analysis with the behavior expected by miR-204 targets after its overexpression and knockdown. With this approach combined with a correlative analysis of the putative targets, we identified a wider set of miR-204 target genes belonging to different pathways. Together, these approaches confirmed that miR-204 has a key role in eye development and further highlighted its putative function in neural differentiation processes, including axon guidance as supported by in vivo functional studies. Together, our results demonstrate the advantage of integrating next-generation sequencing and bioinformatics approaches to investigate miRNA biology and provide new important information on the role of miRNAs in the control of axon guidance and more broadly in nervous system development. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.Italian Telethon Foundation [TGM11SB2]Peer Reviewe
Germline CDH1 deletions in hereditary diffuse gastric cancer families
No full textCDH1 point or small frameshift mutations can be identified in 30-50% of hereditary diffuse gastric cancer (HDGC) families. We hypothesized that CDH1 genomic rearrangements would be found in HDGC and identified 160 families with either two gastric cancers in first-degree relatives and with at least one diffuse gastric cancer (DGC) diagnosed before age 50, or three or more DGC in close relatives diagnosed at any age. Sixty-seven carried germline CDH1 point or small frameshift mutations. We screened germline DNA from the 93 mutation negative probands for large genomic rearrangements by Multiplex Ligation-Dependent Probe Amplification. Potential deletions were validated by RT-PCR and breakpoints cloned using a combination of oligo-CGH-arrays and long-range-PCR. In-silico analysis of the CDH1 locus was used to determine a potential mechanism for these rearrangements. Six of 93 (6.5%) previously described mutation negative HDGC probands, from low GC incidence populations (UK and North America), carried genomic deletions (UK and North America). Two families carried an identical deletion spanning 193 593 bp, encompassing the full CDH3 sequence and CDH1 exons 1 and 2. Other deletions affecting exons 1, 2, 15 and/or 16 were identified. The statistically significant over-representation of Alus around breakpoints indicates it as a likely mechanism for these deletions. When all mutations and deletions are considered, the overall frequency of CDH1 alterations in HDGC is â\u88¼46% (73/160). CDH1 large deletions occur in 4% of HDGC families by mechanisms involving mainly non-allelic homologous recombination in Alu repeat sequences. As the finding of pathogenic CDH1 mutations is useful for management of HDGC families, screening for deletions should be offered to at-risk families. © 2009 The Author(s)
Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy
No full textPatients with autism spectrum disorder (ASD) display distinctive neurophysiological characteristics associated with significant cognitive, emotional, and behavioral symptoms. Transcranial direct current stimulation (tDCS) applied to the frontal or temporoparietal lobes has demonstrated potential to reduce the severity of ASD-related symptoms. Recently, the cerebellum has been identified as a brain area involved in ASD pathophysiology. In this open-label pilot study, seven ASD patients aged between 9 and 13 years underwent 20 daily sessions of 20 min cathodal stimulation of the right cerebellar lobe. At the end of the treatment, the Aberrant Behavior Checklist (ABC) scores showed a 25% mean reduction in global severity of symptoms, with a more pronounced reduction in the "social withdrawal and lethargy" (-35%), "hyperactivity and noncompliance" (-26%), and "irritability, agitation, and crying" (-25%) subscales. Minor and no improvement were observed in the "stereotypic behavior" (-18%) and "inappropriate speech" (-0%) subscales, respectively. Improvements were not detected in the two patients who were taking psychotropic drugs during the study. Clinical response showed a symptom-specific time course. Quality of sleep and mood improved earlier than hyperactivity and social withdrawal. The treatment was generally accepted by patients and well tolerated. No serious adverse events were reported. Stimulation also appeared to markedly reduce the severity of tics in a patient with comorbid tic disorder and led to the disappearance of a frontal epileptogenic focus in another patient with a history of seizures. In conclusion, cerebellar tDCS is safe, feasible, and potentially effective in the treatment of ASD symptoms among children. Strategies to improve recruitment and retention are discussed
A new national survey of centers for cognitive disorders and dementias in Italy
No full textIntroduction: A new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic.
Methods: A list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak.
Results: In total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open.
Conclusion: This paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia
The Profile of the Italian Centers for Cognitive Disorders and Dementia in the Context of New Drugs in Alzheimer's Disease
No full textBackground: The wait for the upcoming disease-modifying therapies (DMT) for Alzheimer's disease in Europe is raising questions about the preparedness of national healthcare systems to conduct accurate diagnoses and effective prescriptions. In this article, we focus on the current situation in Italy. Objective: The primary goal is to propose a profile of the Italian Centers for Cognitive Disorders and Dementias (CCDDs) that could be taken into consideration by regional and autonomous provincial authorities when deciding on the prescribing centers for DMT. Methods: Based on responses to a national survey on CCDDs in Italy, we identified the CCDDs that meet the requirements for effective prescription: 1) Multidisciplinary team; 2) Minimum Core Test for the neuropsychological assessment; 3) PET, CSF, and Brain MRI assessments. Univariate and multivariate comparisons were conducted between CCDDs that met the criteria and the others. Results: Only 10.4% of CCDDs met the requirements for effective DMT prescription, mainly located in Northern Italy. They are also characterized by longer opening hours, a higher number of professionals, a university location, and a higher frequency of conducting genetic tests, and could potentially result in prescribing centers. Conclusions: The findings suggest that the Italian national healthcare system may benefit from further enhancements to facilitate the effective prescription of DMTs. This could involve initiatives to reduce fragmentation, ensure adequate resources and equipment, and secure sufficient funding to support this aspect of healthcare delivery
Neuropsychological tests at the Italian Centers for Cognitive Disorders and Dementias: results from a survey on 450 specialized services
No full textBackground: The Italian Fund for Alzheimer’s and other dementias approved in 2020 enabled the conducting of a survey in the Italian Centers for Cognitive Disorders and Dementias (CCDDs) to analyse the organization, the administrative features and the professionals’ characteristics. Aims: To investigate the current use of neuropsychological (NP) tests in Italian CCDDs and the association between the use of a basic set of tests for neuropsychological assessment (NPA) and organizational/structural characteristics of CCDDs. Methods: A survey was conducted with an online questionnaire in all CCDDs between July 2022 and February 2023. To verify the use of a comprehensive NPA in the diagnosis of cognitive disorders and dementia, we identified a minimum core test (MCT). Results: The CCDDs using a Minimum Core Test (MCT) significantly increased from 45.7% in 2015 to the current 57.1%. Territorial CCDDs using MCT significantly increased from 24.9% in 2015 to 37% in 2022 (p = 0.004). As multivariable results, the presence of psychologist/neuropsychologist in the staff and the University-based/IRCCS CCDDs increased the probability of using MCT (OR = 9.2; 95% CI 5.6–15.0; p < 0.001 and OR = 5.4; 95% CI 1.9–15.9; p = 0.002, respectively), while CCDDs in Southern Italy-Islands showed a lower probability than those in the North (OR = 0.4; 95% CI 0.2–0.7; p = 0.001). Discussion: Almost half of CCDDs (43%) do not use MCT in their clinical practice. The presence of the psychologist/neuropsychologist on the staff has a key role in the adoption of MCT and regional differences have increased over the past years. NPA is crucial in the diagnostic process and in characterizing risk profiles in order to implement targeted interventions for risk reduction. Conclusions: Our results could help to identify good practices aimed at improving dementia diagnosis. An intervention by health policymakers is urgently needed with the aim of improving diagnostic appropriateness and overcoming regional differences
