Background Glioblastoma (GBM) stemlike cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted delta-like homolog 1 gene‒type III iodothyronine deiodinase gene (DLK-DIO3) region on chromosome 14q32 in GBM pathogenesis. Methods Real-time PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression, and reverse-phase protein array profiles were used to investigate the tumor suppressor function of the maternally expressed 3 gene (MEG3). Results Loss of expression of genes and noncoding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared with normal brain. This downregulation is mainly mediated by epigenetic silencing. Kaplan–Meier analysis indicated that low expression of MEG3 and MEG8 long noncoding (lnc)RNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration, and colony formation and decreases in vivo tumor growth, reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and epithelial-to-mesenchymal transition (EMT). Conclusion In GBM, MEG3 acts as a tumor suppressor mainly regulating cell adhesion, EMT, and cell proliferation, thus providing a potential candidate for novel GBM therapies.

Background:Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the degeneration of the second motor-neuron. The phenotype ranges from very severe to very mild forms. All patients have the homozygous loss of the SMN1 gene and a variable number of SMN2 (generally two-to-four copies), inversely related with the severity. The amazing results of the available treatments have made compelling the need of prognostic biomarkers to predict the progression trajectories of patients. Beside the SMN2 products, few other biomarkers have been evaluated so far, including some miRs.Methods:We performed whole miRNome analysis of muscle samples of patients and controls (14 biopsies and 9 cultures). The levels of muscle differentially expressed miRs were evaluated in serum samples (51 patients and 37 controls) and integrated with SMN2 copies, SMN2-full length transcript levels in blood and age (SMA-score). Results:Over 100 miRs were differentially expressed in SMA muscle; three of them (HSA-miR-181a-5p, -324-5p, -451a; SMA-miRs) were significantly up-regulated in serum of patients. The severity predicted by the SMA-score was related with that of the clinical classification at a correlation coefficient of 0.87 (p<10-5).Conclusions:miRNome analyses suggest the primary involvement of skeletal muscle in SMA pathogenesis; the SMA-miRs are likely actively released in the blood flow, even if their function and target cells require to be elucidated. The accuracy of the SMA-score needs to be verified in replicative studies: if confirmed, its use could be crucial for the routine prognostic assessment, also in pre-symptomatic patients. Funding:Telethon Italia (grant # GGP12116).

BackgroundSpinal muscular atrophy (SMA) is due to the homozygous absence ofSMN1in around 97% of patients, independent of the severity (classically ranked into types I–III). The high genetic homogeneity, coupled with the excellent results of presymptomatic treatments of patients with each of the three disease-modifying therapies available, makes SMA one of the golden candidates to genetic newborn screening (NBS) (SMA-NBS). The implementation of SMA in NBS national programmes occurring in some countries is an arising new issue that the scientific community has to address. We report here the results of the first Italian SMA-NBS project and provide some proposals for updating the current molecular diagnostic scenario.MethodsThe screening test was performed by an in-house-developed qPCR assay, amplifyingSMN1andSMN2. Molecular prognosis was assessed on fresh blood samples.ResultsWe found 15 patients/90885 newborns (incidence 1:6059) having the followingSMN2genotypes: 1 (one patient), 2 (eight patients), 2+c.859G>C variant (one patient), 3 (three patients), 4 (one patient) or 6 copies (one patient). Six patients (40%) showed signs suggestive of SMA at birth. We also discuss some unusual cases we found.ConclusionThe molecular diagnosis of SMA needs to adapt to the new era of the disease with specific guidelines and standard operating procedures. In detail, SMA diagnosis should be felt as a true medical urgency due to therapeutic implications;SMN2copy assessment needs to be standardised; commercially available tests need to be improved for higherSMN2copies determination; and theSMN2splicing-modifier variants should be routinely tested in SMA-NBS.

Background and aims The effect of surgical treatment for spontaneous intracerebral hemorrhage (ICH) remains uncertain. We conducted an observational retrospective cohort study on supra-centimeter spontaneous ICH treated with either neurosurgical or conservative management. The baseline demographics and risk factors were correlated with in-hospital mortality and 3 and 6-month survival rates stratified by management. Methods We included all patients with evidence of spontaneous ICH > 1 cm detected by CT and admitted between august 2020 and march 2021 to the “SMM” Hospital in Perugia. Results Onehundredandtwentytwo patients were included in the study, and 45% (n.55) were surgically treated. The mean age was 71.9 ± 15.3, and 61% (n.75) were males. Intra-hospital mortality ended up being 31% (n.38), 3 months-survival was 63% (n.77) and 6 months-survival was 60% (n.73). From the multivariate analysis of the surgical patients versus medical patient, we observed that the surgical patients were younger (67.5 ± 14.9 vs 75.5 ± 14.7 y; OR 0.87; Cl 95% 0.85–0.94; p 0.001), with greater ICH volume at the onset (61 ± 39.4 cc vs 51 ± 64 cc; OR 1.03; Cl 95% 1.005–1.07; p 0.05), more midline shift (7.61 ± 5.54 mm vs 4.09 ± 5.88 mm; OR 1.37; Cl 95% 1.045–1.79; p 0.023), and a higher ICH score (3 vs 2 mean ICH score; OR 21.12; Cl 95% 2.6–170.6; p 0.004). Intra-hospital mortality in the surgical group and in the conservative treatment group was respectively 33% vs 30%, 3 month-survival was 64% vs 63% and 6 month- survival were 60% in both groups. Conclusions Our patient cohort shows no overall benefit from surgery over conservative treatment, but surgical patients were younger and had larger ICH volume.

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