Molecular expression and characterisation of non-coding RNA in tumor growth and invasiveness of glioblastoma stem-like cells

Glioblastoma (GBM) is an aggressive form of glioma in adults that owes its worse characteristics, like recurrence and resistance to therapy, mainly to GBM stem-like cells (GSCs). In vitro studies employ GSCs to generate self-renewing cell lines that can mimic the original tumor. We performed analyses on our collection of patient-derived GSC lines to study long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs), important oncogenic drivers and tumor suppressors in many tumors. Our work revealed that the microRNA miR-370-3p is significantly down-regulated in GSCs compared to a normal control and, when restored, the proliferation, migration and clonogenic abilities of GSCs are impaired. Another effect of miR-370-3p restoration became clear after gene expression analyses, which identified several transcripts involved in Epithelial to Mesenchymal Transition (EMT), and Hypoxia signalling pathways. Surprisingly, among the genes down-regulated as a result of miR-370-3p restored expression, we found more genes correlated to GBM, like the EMT-inducer high-mobility group AT-hook 2 (HMGA2), the master transcriptional regulator of the adaptive response to hypoxia, Hypoxia-inducible factor (HIF)1A, and the long non-coding RNA (lncRNA) Nuclear Enriched Abundant Transcript (NEAT1). In particular, NEAT1 is an oncogenic lncRNA, associated to worse prognosis for several cancers: we found by luciferase assay that miR-370-3p directly binds NEAT1, so that the expression levels of these ncRNAs are inversely correlated in GSCs. Our results suggest that a complex “cascade” interplaying among different ncRNAs is partially responsible for GBM’s most malignant features. Indeed, miR-370-3p shows a prominent tumor-suppressor function by targeting mRNAs involved in EMT, in hypoxia pathways, and cell growth and the invasiveness enhancer NEAT1, making this microRNA another promising candidate for novel GBM treatments

Chest CT Features of COVID-19 in Rome, Italy

Background The standard for diagnosis of SARS-CoV-2 virus is reverse transcription polymerase chain reaction (RT-PCR) test, but chest CT may play a complimentary role in the early detection of COVID-19 pneumonia. Purpose To investigate CT features of patients with COVID-19 in Rome, Italy, and to compare the accuracy of CT with RT-PCR. Methods In this prospective study from March 4, 2020, until March 19, 2020, consecutive patients with suspected COVID-19 infection and respiratory symptoms were enrolled. Exclusion criteria were: chest CT with contrast medium performed for vascular indications, patients who refused chest CT or hospitalization, and severe CT motion artifact. All patients underwent RT-PCR and chest CT. Diagnostic performance of CT was calculated using RT-PCR as reference. Chest CT features were calculated in a subgroup of RT-PCR-positive and CT-positive patients. CT features of hospitalized patients and patient in home isolation were compared by using Pearson chi squared test. Results Our study population comprised 158 consecutive study participants (83 male and 75 female, mean age 57 y ±17). Fever was observed in 97/158 (61%), cough in 88/158 (56%), dyspnea in 52/158 (33%), lymphocytopenia in 95/158 (60%), increased C-reactive protein level in 139/158 (88%), and elevated lactate dehydrogenase in 128/158 (81%) study participants. Sensitivity, specificity, and accuracy of CT were 97% (60/62)[95% IC, 88-99%], 56% (54/96)[95% IC,45-66%] and 72% (114/158)[95% IC 64-78%], respectively. In the subgroup of RT-PCR-positive and CT-positive patients, ground-glass opacities (GGO) were present in 58/58 (100%), multilobe and posterior involvement were both present in 54/58 (93%), bilateral pneumonia in 53/58 (91%), and subsegmental vessel enlargement (> 3 mm) in 52/58 (89%) of study participants. Conclusion The typical pattern of COVID-19 pneumonia in Rome, Italy, was peripherally ground-glass opacities with multilobe and posterior involvement, bilateral distribution, and subsegmental vessel enlargement (> 3 mm). Chest CT sensitivity was high (97%) but with lower specificity (56%)

Histologic analysis of idiopathic pulmonary fibrosis by morphometric and fractal analysis

: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (Df), and every pathological insult, distorting the normal lung structure, could result in Df variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched "healthy" control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate Df and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that Df was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high Df values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that Df may serve as a potential novel prognostic marker for IPF. The scalability of Df measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological Df in UIP pattern, as well as a significant association between Df and FF density. Furthermore, our study demonstrates the scalability and self-similarity of Df measurements across different biopsy types, including surgical and smaller specimens

Insights into cognitive and behavioral comorbidities of SLC6A1-related epilepsy: five new cases and literature review

IntroductionSLC6A1 pathogenic variants have been associated with epilepsy and neurodevelopmental disorders. The clinical phenotype includes different seizure types, intellectual disability, and psychiatric symptoms affecting mood and behavior. Few data regarding neuropsychological features have been described, and details on cognitive profiles are often missing due to the lack of standardized tests.MethodsWe retrospectively reviewed the neuropsychological assessments of five subjects carrying heterozygous missense genetic variants in SLC6A1. We also collected data on epileptic features, EEGs, and brain MRIs. Additionally, we reviewed neuropsychological data from 204 previously reported patients with SLC6A1 pathogenic variants.ResultsIn our series, at the last evaluation (median 12.6 years), three patients had borderline intellectual functioning, one patient had mild cognitive impairment, and one patient presented with a moderate cognitive disability. Three out of five patients underwent at least two neuropsychological evaluations, which revealed a worsening of cognitive functions over time. We detected attention deficits in all patients. In addition, we observed anxiety, disruptive behavior disorder, emotional instability, and hetero aggressiveness. We also performed a literature review that highlighted that most of the patients with SLC6A1 pathogenic variants have mild-to-moderate intellectual disability and that one-third of cases have autistic traits.DiscussionBased on the literature review and the detailed description of our cases, we conclude that patients with SLC6A1-related epilepsy mostly present with mild-to-moderate intellectual disability, often associated with attention disorders. Such symptoms may worsen over time. Periodic standardized neuropsychological tests may be useful tools to follow development over time, and patient-specific rehabilitation programs could be tailored consistently

Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients

BACKGROUND: Several immune mechanisms activate in COVID-19 pathogenesis. Usually, coronavirus infection is characterized by dysregulated host immune responses, interleukine-6 increase, hyper-activation of cytotoxic CD8 T lymphocytes. Interestingly, Vitamin D deficiency has been often associated with altered immune responses and infections. In the present study, we evaluated Vitamin D plasma levels in patients affected with different lung involvement during COVID-19 infection.METHODS: Lymphocyte phenotypes were assessed by flow cytometry. Thoracic CT scan involvement was obtained by an image analysis program.RESULTS: Vitamin D levels were deficient in (80%) of patients, insufficient in (6.5%) and normal in (13.5%). Patients with very low Vitamin D plasma levels had more elevated D-Dimer values, a more elevated B lymphocyte cell count, a reduction of CD8+T lymphocytes with a low CD4/CD8 ratio, more compromised clinical findings (measured by LIPI and SOFA scores) and thoracic CT scan involvement.CONCLUSIONS: Vitamin D deficiency is associated with compromised inflammatory responses and higher pulmonary involvement in COVID-19 affected patients. Vitamin D assessment, during COVID-19 infection, could be a useful analysis for possible therapeutic interventions.TRIAL REGISTRATION: 'retrospectively registered'

Monitoring and predicting the risk of violence in residential facilities. No difference between patients with history or with no history of violence

none34noopende Girolamo, Giovanni; Buizza, Chiara; Sisti, Davide; Ferrari, Clarissa; Bulgari, Viola; Iozzino, Laura; Boero, Maria Elena; Cristiano, Giuseppe; De Francesco, Alessandra; Giobbio, Gian Marco; Maggi, Paolo; Rossi, Giuseppe; Segalini, Beatrice; Candini, Valentina; Andreose, Suor; Basso, Pasquale; Beneduce, Rossella; Bertolotti, Pietro; Braida, Vanda; Bonelli, Marina; Bongiorno, Fanny; Bussi, Riccardo; Castagno, Elisa; Dominicis, Fabio; Ghersi, Loredana; Greppo, Stefania; Sodano, Alessandro Jaretti; Leporatti, Massimo; Presti, Eleonora Lo; Milone, Valeria; Panigada, Fausto; Pasquadibisceglie, Livia; Rigamonti, Danilo; Rillosi, Lucianade Girolamo, Giovanni; Buizza, Chiara; Sisti, Davide; Ferrari, Clarissa; Bulgari, Viola; Iozzino, Laura; Boero, Maria Elena; Cristiano, Giuseppe; De Francesco, Alessandra; Giobbio, Gian Marco; Maggi, Paolo; Rossi, Giuseppe; Segalini, Beatrice; Candini, Valentina; Andreose, Suor; Basso, Pasquale; Beneduce, Rossella; Bertolotti, Pietro; Braida, Vanda; Bonelli, Marina; Bongiorno, Fanny; Bussi, Riccardo; Castagno, Elisa; Dominicis, Fabio; Ghersi, Loredana; Greppo, Stefania; Sodano, Alessandro Jaretti; Leporatti, Massimo; Presti, Eleonora Lo; Milone, Valeria; Panigada, Fausto; Pasquadibisceglie, Livia; Rigamonti, Danilo; Rillosi, Lucian

The appropriate management of an appendiceal mucocele

Appendicectomy is one of the most commonly performed surgical procedures. Appendiceal mucocele is a relative rare disease, but appropriate management is critical. Indeed, the intact removal of a mucocele represents a curative treatment; conversely, a rupture may result in the spread of epithelial cells throughout the peritoneal cavity (pseudomyxoma peritonei). We report a case of a 61-year-old woman, admitted to our department, who underwent resection of an appendiceal mucocele, focusing, in the discussion, on the clinical and surgical management of this disease