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Diagnoses of primary malignant mesenchymal brain tumors are a challenge for pathologists. Here, we report the case of a 52-year-old man with a primary brain tumor, histologically diagnosed as a high-grade glioma, not otherwise specified (NOS). The patient underwent two neurosurgeries in several months, followed by radiotherapy and chemotherapy. We re-examined the tumor samples by methylome profiling. Methylome analysis revealed an epi-signature typical of a primary intracranial sarcoma, DICER1-mutant, an extremely rare tumor. The diagnosis was confirmed by DNA sequencing that revealed a mutation in DICER1 exon 25. DICER1 mutations were not found in the patient's blood cells, thus excluding an inherited DICER1 syndrome. The methylome profile of the DICER1 mutant sarcoma was then compared with that of a high-grade glioma, a morphologically similar tumor type. We found that several relevant regions were differentially methylated. Taken together, we report the morphological, epigenetic, and genetic characterization of the sixth described case of an adult primary intracranial sarcoma, DICER1-mutant to-date. Furthermore, this case report underscores the importance of methylome analysis to refine primary brain tumor diagnosis and to avoid misdiagnosis among morphologically similar subtypes.

Recessive X-linked disorders may occasionally evolve in clinical manifestations of variable severity also in female carriers. For some of such diseases, the frequency of the symptoms’ appearance during women’s life may be particularly relevant. This phenomenon has been largely attributed to the potential skewness of the X-inactivation process leading to variable phenotypes. Nonetheless, in many cases, no correlation with X-inactivation unbalance was demonstrated. However, methods for analyzing skewness have been mainly limited to Human Androgen Receptor methylation analysis (HUMARA). Recently, the X-inactivation process has been largely revisited, highlighting the heterogeneity existing among loci in the epigenetic state within inactive and, possibly, active X-chromosomes. We reasoned that gene-specific and ultra-deep DNA methylation analyses could greatly help to unravel details of the X-inactivation process and the roles of specific X genes inactivation in disease manifestations. We recently provided evidence that studying DNA methylation at specific autosomic loci at a single-molecule resolution (epiallele distribution analysis) allows one to analyze cell-to-cell methylation differences in a given cell population. We here apply the epiallele analysis at two X-linked loci to investigate whether females show allele-specific epiallelic patterns. Due to the high potential of this approach, the method allows us to obtain clearly distinct allele-specific epiallele profiles.

Nel corso dei primi anni di scolarizzazione il bambino è impegnato per la maggior parte del tempo in attività di scrittura. È quindi importante poter valutare il grado di apprendimento delle competenze ortografiche e intervenire, in presenza di difficoltà, con un trattamento mirato. Sulla base del modello teorico a due vie, il test DDO-2 permette di valutare le capacità di scrittura lessicale e sub lessicale in bambini della scuola primaria e secondaria di primo grado, attraverso un dettato di 160 stimoli suddivisi in quattro sezioni in base alla categoria di parole proposte. Questa nuova edizione presenta inoltre una versione breve del test (60 stimoli), uno strumento di somministrazione più agile che rispetta i principi di costruzione e attendibilità della versione integrale. Il DDO-2 consente di effettuare lo scoring automatico tramite il software scaricabile dal sito http://risorseonline.erickson.it/, che fornisce una valutazione sia della prestazione complessiva, sia delle prestazioni ai singoli subset di stimoli dettati.

Introduction Although spelling difficulties are constantly associated with developmental dyslexia, they have been largely neglected by the majority of studies in this area. This study analyzes spelling impairments in developmental dyslexia across school grades in Italian, a language with high grapheme-to-phoneme correspondence. Methods The performances of 33 Italian dyslexic children attending Grades 3 and 5 were compared with those of age-matched control participants. Writing abilities were investigated through a spelling test that included regular words with one-sound-to-one-letter correspondence, regular words requiring the application of context-sensitive conversion rules, words with unpredictable transcription and nonwords with one-sound-to-one-letter correspondence. Results Both accuracy and error analyses indicate that the spelling impairment assumes different characteristics at different grades: Grade 3 children showed an undifferentiated spelling deficit (involving regular words, regular nonwords and words with unpredictable spelling), whereas the fifth graders were prevalently impaired in writing words with unpredictable transcription. The error analysis confirms these results, with third graders producing a high rate of all types of errors (i.e., phonologically plausible, simple and context-sensitive conversion errors), whereas most errors committed by fifth graders were phonologically plausible. Conclusions Results are coherent with the hypothesis that dyslexic children learning a shallow orthography suffer from delayed acquisition and some fragility of the sub-word level routine, together with a severe and long-lasting deficit of orthographic lexical acquisition.

Background: There is mounting evidence of the presence of chronic stress among children during primary school: girls and boys under the age of 15 years often experience anxiety, irritability and sleeping problems with negative consequences on scholastic climate and the spread of bullying and dropping out of school. The promotion of emotion regulation within school environment through innovative didactic methodologies represents a valuable tool for teachers and parents to reduce emotional distress and associated risk behaviours and to promote wellbeing. Aim: Our research aims to explore the psychological and biological consequences of teaching emotional training in an experimental group of Italian Primary School children. Methods: A sample of pupils (81 children aged between 6 and 8) was divided into an experimental group (33 subjects) and a control group (30 subjects). A further advanced group of 18 subjects, who have experienced the method in the previous school year, was also included. The experimental study lasted one school year (from October 2021 to May 2022). The following psychological tests were administered to all groups: TEC (Test of Emotion Comprehension) to measure the children's different emotional abilities and the Projective test (PT) 'A person in the rain', to identify the coping skills of children in a stressful condition. Morning salivary cortisol, IL-6 and TNF-alpha assays were conducted in all three groups. Psychological and biological tests were administered at the beginning of the study and at the end of the study. Results: The MR-Anova model for TEC score showed that there was not a significant group effect [Fgroup = 2.24, p = 0.114]. Pairwise comparisons showed that mean score significantly increased only in the Experimental group (pB < 0.001) and at the end of the project there was a significant difference between Experimental group and Control group (pB = 0.012). The mean score of PT test increased significantly from baseline to the end of the project for the Experimental group (pB < 0.001) and for the Advanced group (pB = 0.004). At the end of the project, there were significant differences between the Experimental group and the Control group (pB = 0.004) and between the Advanced group and the Control group (pB < 0.001). Salivary cortisol analysis revealed a significant effect between subjects [Fgroup = 9.66; p < 0.001] and significant effects within subjects with the main effect of the time [Ftime = 35.41; p < 0.001] and the significant interaction “time x group” [Ftimexgroup = 3.38; p = 0.040]. Pairwise comparisons showed that cortisol levels decreased significantly over time only in the Experimental group (pB < 0.001). Regarding to IL-6 levels, there was not a significant effect between subjects [Fgroups = 0.0481; p = 0.953]. The mean level decreased significantly for each group from baseline to post project (pB < 0.001). With respect to TNF-alpha levels, the mean levels decreased over time for all groups (pB = 0.006 for Experimental group; pB < 0.001 either for the Advanced or Control group). Conclusion: the results documented in the experimental groups who experienced didactics of emotion for at least one school year show a significant increase in children's ability to cope with reality, stress and anxiety, and an improvement of their emotional competence. Meanwhile, a significant reduction in the amount of salivary cortisol was observed in the experimental group at the end of the scholastic year; meantime a stable reduced amount of salivary cortisol in advanced group throughout the project was also observed. These findings show that an intervention through an emotional education program is able to regulate interpersonal skills and the stress axis response.

Glioblastoma, the most common and heterogeneous tumor affecting brain parenchyma, is dismally characterized by a very poor prognosis. Thus, the search of new, more effective treatments is a vital need. Here, we will review the druggable epigenetic features of glioblastomas that are, indeed, currently explored in preclinical studies and in clinical trials for the development of more effective, personalized treatments. In detail, we will review the studies that have led to the identification of epigenetic signatures, IDH mutations, MGMT gene methylation, histone modification alterations, H3K27 mutations, and epitranscriptome landscapes of glioblastomas, in each case discussing the corresponding targeted therapies and their potential efficacy. Finally, we will emphasize how recent technological improvements permit to routinely investigate many glioblastoma epigenetic biomarkers in clinical practice, further enforcing the hope that personalized drugs, targeting specific epigenetic features, could be in future a therapeutic option for selected patients.