Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues

Preservation of modern and MIS 5.5 erosional landforms and biological structures as sea level markers : a matter of luck?

The Mediterranean Basin is characterized by a significant variability in tectonic behaviour, ranging from subsidence to uplifting. However, those coastal areas considered to be tectonically stable show coastal landforms at elevations consistent with eustatic and isostatic sea level change models. In particular, geomorphological indicators—such as tidal notches or shore platforms—are often used to define the tectonic stability of the Mediterranean coasts. We present the results of swim surveys in nine rocky coastal sectors in the central Mediterranean Sea using the Geoswim approach. The entire route was covered in 22 days for a total distance of 158.5 km. All surveyed sites are considered to have been tectonically stable since the last interglacial (Marine Isotope Stage 5.5 [MIS 5.5]), because related sea level markers fit well with sea level rise models. The analysis of visual observations and punctual measurements highlighted that, with respect to the total length of surveyed coast, the occurrence of tidal notches, shore platforms, and other indicators accounts for 85% of the modern coastline, and only 1% of the MIS 5.5 equivalent. Therefore, only 1% of the surveyed coast showed the presence of fossil markers of paleo sea levels above the datum. This significant difference is mainly attributable to erosion processes that did not allow the preservation of the geomorphic evidence of past sea level stands. In the end, our research method showed that the feasibility of applying such markers to define long-term tectonic behaviour is much higher in areas where pre-modern indicators have not been erased, such as at sites with hard bedrock previously covered by post-MIS 5.5 continental deposits, e.g., Sardinia, the Egadi Islands, Ansedonia, Gaeta, and Circeo. In general, the chances of finding such preserved indicators are very low.peer-reviewe

Novità in Radioterapia: Flattening Filter Free

Il Flattening Filter (FF), ossia il filtro di attenuazione, omogenizza energia ed intensità del fascio di Raggi X durante l'erogazione di un trattamento radioterapico. Nei trattamenti stereotassici (trattamenti che prevedono la somministrazione di elevate dosi di radiazioni in una singola o in un massimo di 5 sedute ad un piccolo volume), il FF determina una limitazione in termini di durata del trattamento. Quando è presente il FF, i fotoni vengono da esso assorbiti, con conseguente riduzione dell'efficienza del fascio, e diffusi con un aumento della contaminazione dovuta alla produzione di neutroni secondari. Eliminando il FF (FFF=Flattening Filter-Free), il numero di impulsi al secondo non cambia, ma cambia la dose per impulso, che aumenta notevolmente. Si determina così un aumento sostanziale del dose-rate, con focalizzazione del fascio (beam stearing), e conseguente riduzione dei tempi di erogazione del trattamento. Questa conseguenza risulta particolarmente vantaggiosa nelle terapie stereotassiche, in particolari in quelle polmonari erogate con l'ausilio del gating respiratorio, in cui è possibile elevare la dose nella fase "on" del fascio nel minor tempo possibile, riducendo il rischio di movimento intrafrazione con conseguente aumento dell'indice terapeutico del trattamento. Ma quali sono le conseguenze in termini di copertura del target, di effetto build up e di cancerogenesi radioindotta

Identification and evaluation of parameters for the prevention of pressure ulcers in hospitalized patients

The observation and prevention of decubitus sores of patients hospitalized during rehabilitation is an important issue and the commercial devices traditionally used for this purpose seem not sufficient. Therefore, it is necessary to design a new algorithm, implemented in Labview, for the evaluation of these indicators. The program has been tested on a healthy subject and then a protocol has been written to verify the first results on patients. The software shows a good behavior even in a clinical environment and it proposes itself as a tool for the evaluation of pressure ulcers in hospitals and to help medical staff to better take care of such a problem

Temozolomide and Radiotherapy versus Radiotherapy Alone in High Grade Gliomas: A Very Long Term Comparative Study and Literature Review

Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ. Materials and Methods. In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ. Results. Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11. Conclusions. The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis

Spontaneous ilio-psoas haematomas (IPHs): a warning for COVID-19 inpatients

AbstractIntroduction Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment.Materials and methods We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy.Results Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis.Conclusions Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients.KEY MESSAGECritically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended.Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases.An incidence of 7.6 cases per 1000 admission of IPHs was reported.Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80–320). Their median age was 68 years (IQR, 56–78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (<68 years), mild disease (admission to low-intensity departments) and early treatment (<7 days from symptoms onset) with high nAb titer (≥320) CCP were found as independently associated with a favorable response to CCP treatment. No safety concerns were recorded, with a rate of CCP-related adverse reactions (all of mild intensity) of 1.3%. In our real-life experience, the first in the western world, early administration of high-titer CCP was a safe and effective treatment for hospitalized COVID-19 patients