LACK OF AN ASSOCIATION BETWEEN INHERITED THROMBOPHILIC RISK FACTORS AND IDIOPATIC SUDDEN SENSORINEURAL HEARING LOSS IN ITALIAN PATIENTS

Objectives: We investigated the presence of congenital thrombophilic risk factors in a population of consecutive Italian patients affected by idiopathic sudden sensorineural hearing loss (SSNHL). Methods: We investigated 48 patients with idiopathic SSNHL for the presence of congenital thrombophilic risk factors. The factor V Leiden G1691A, the prothrombin G20210A allele, and methylenetetrahydrofolate reductase (MTHFR) C677T genotypes were investigated. Allele frequencies and genotype distribution of all factors found in patients were compared to those of 48 healthy subjects of the same ethnic background by Chi2 and odds-ratio analysis. Odds ratios and 95% confidence intervals were calculated for allele and genotype frequencies of all thrombophilia variants. Statistical significance was accepted with a p value of less than .05. We also performed the following blood tests: hemacytometric analysis including platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, erythrocyte sedimentation rate, C-reactive protein, protein S, protein C, antithrombin III, and activated protein C resistance. Results: In our series, we did not find an association between SSNHL and abnormal levels of antithrombin III, protein C, protein S, D-dimer, or fibrinogen; activated protein C resistance; or factor V G1691A, prothrombin G20210A, or MTHFR C677T mutations. Conclusions: At present, the few studies regarding genetic polymorphisms of congenital thrombophilic factors in SSNHL are not conclusive. According to our data, factor V G1691A, prothrombin G20210A, and MTHFR C677T variants should be not considered risk factors for SSNHL. Further large prospective studies are needed to provide currently lacking information and to improve our knowledge in the field before we recommend the determination of genetic polymorphism in SSNHL as routine practice

Multiplex Networks for Early Diagnosis of Alzheimer's Disease

Analysis and quantification of brain structural changes, using Magnetic Resonance Imaging (MRI), are increasingly used to define novel biomarkers of brain pathologies, such as Alzheimer's disease (AD). Several studies have suggested that brain topological organization can reveal early signs of AD. Here, we propose a novel brain model which captures both intra- and inter-subject information within a multiplex network approach. This model localizes brain atrophy effects and summarizes them with a diagnostic score. On an independent test set, our multiplex-based score segregates (i) normal controls (NC) from AD patients with a 0.86±0.01 accuracy and (ii) NC from mild cognitive impairment (MCI) subjects that will convert to AD (cMCI) with an accuracy of 0.84±0.01. The model shows that illness effects are maximally detected by parceling the brain in equal volumes of 3, 000 mm3 (“patches”), without any a priori segmentation based on anatomical features. The multiplex approach shows great sensitivity in detecting anomalous changes in the brain; the robustness of the obtained results is assessed using both voxel-based morphometry and FreeSurfer morphological features. Because of its generality this method can provide a reliable tool for clinical trials and a disease signature of many neurodegenerative pathologies

Epha3 acts as proangiogenic factor in multiple myeloma

This study investigates the role of ephrin receptor A3 (EphA3) in the angiogenesis of Multiple Myeloma (MM) and the effects of a selective target of EphA3 by a specific monoclonal antibody on primary bone marrow endothelial cells (ECs) of MM patients.EphA3 mRNA and protein were evaluated in ECs of MM patients (MMECs), in ECs of patients with monoclonal gammopathies of undetermined significance (MGECs) and in ECs of healthy subjects (control ECs). The effects of EphA3 targeting by mRNA silencing (siRNA) or by the anti EphA3 antibody on the angiogenesis were evaluated. We found that EphA3 is highly expressed in MMECs compared to the other EC types. Loss of function of EphA3 by siRNA significantly inhibited the ability of MMECs to adhere to fibronectin, to migrate and to form tube like structures in vitro, without affecting cell proliferation or viability. In addition, gene expression profiling showed that knockdown of EphA3 down modulated some molecules that regulate adhesion, migration and invasion processes. Interestingly, EphA3 targeting by an anti EphA3 antibody reduced all the MMEC angiogenesis-related functions in vitro. In conclusion, our findings suggest that EphA3 plays an important role in MM angiogenesis

A Pyrazolo[3,4-d]pyrimidine compound inhibits Fyn phosphorylation and induces apoptosis in natural killer cell leukemia

Natural killer (NK) cell neoplasms are characterized by clonal proliferation of cytotoxic NK cells. Since there is no standard treatment to date, new therapeutic options are needed, especially for NK aggressive tumors. Fyn tyrosine kinase has a key role in different biological processes, such as cell growth and differentiation, being also involved in the pathogenesis of hematologic malignancies. Our previous studies led us to identify 4c pyrazolo[3,4-d]pyrimidine compound capable of inhibiting Fyn activation and inducing apoptosis in different cancer cell lines. Here we investigated the presence of Fyn and the effect of its inhibitor in NK malignant cells. Firstly, we showed Fyn over-expression in NK leukemic cells compared to peripheral blood mononuclear cells from healthy donors. Subsequently, we demonstrated that 4c treatment reduced cell viability, induced caspase 3-mediate apoptosis and cell cycle arrest in NK cells. Moreover, by inhibiting Fyn phosphorylation, 4c compound reduced Akt and P70 S6 kinase activation and changed the expression of genes involved in cell death and survival in NK cells. Our study demonstrated that Fyn is involved in the pathogenesis of NK leukemia and that it could represent a potential target for this neoplasm. Moreover, we proved that Fyn inhibitor pyrazolo[3,4-d]pyrimidine compound, could be a started point to develop new therapeutic agents

Understanding 6th-century barbarian social organization and migration through paleogenomics.

Despite centuries of research, much about the barbarian migrations that took place between the fourth and sixth centuries in Europe remains hotly debated. To better understand this key era that marks the dawn of modern European societies, we obtained ancient genomic DNA from 63 samples from two cemeteries (from Hungary and Northern Italy) that have been previously associated with the Longobards, a barbarian people that ruled large parts of Italy for over 200 years after invading from Pannonia in 568 CE. Our dense cemetery-based sampling revealed that each cemetery was primarily organized around one large pedigree, suggesting that biological relationships played an important role in these early medieval societies. Moreover, we identified genetic structure in each cemetery involving at least two groups with different ancestry that were very distinct in terms of their funerary customs. Finally, our data are consistent with the proposed long-distance migration from Pannonia to Northern Italy.This work was supported by National Science Foundation award #1450606, the Anneliese Maier Research Award of the Alexander von Humboldt Foundation, the Max Planck Society, the German Federal Ministry for Education and Research, the Swedish Riksbankens Jubieleumfond, the Gerard B. Lambert Foundation, the Institute for Advanced Study Director’s Office, and the Italian Ministry for University and Research Department of Excellence Program

Timing of surgery following SARS‐CoV‐2 infection: an international prospective cohort study

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4–1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0–2 weeks, 3–4 weeks and 5–6 weeks of the diagnosis (odds ratio (95%CI) 4.1% (3.3–4.8), 3.9% (2.6–5.1) and 3.6% (2.0–5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5% (0.9– 2.1%)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2–8.7) vs. 2.4% (95%CI 1.4–3.4) vs. 1.3% (95%CI 0.6–2.0%), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay

"Help! I Need Somebody": Music as a Global Resource for Obtaining Wellbeing Goals in Times of Crisis.

Music can reduce stress and anxiety, enhance positive mood, and facilitate social bonding. However, little is known about the role of music and related personal or cultural (individualistic vs. collectivistic) variables in maintaining wellbeing during times of stress and social isolation as imposed by the COVID-19 crisis. In an online questionnaire, administered in 11 countries (Argentina, Brazil, China, Colombia, Italy, Mexico, the Netherlands, Norway, Spain, the UK, and USA, N = 5,619), participants rated the relevance of wellbeing goals during the pandemic, and the effectiveness of different activities in obtaining these goals. Music was found to be the most effective activity for three out of five wellbeing goals: enjoyment, venting negative emotions, and self-connection. For diversion, music was equally good as entertainment, while it was second best to create a sense of togetherness, after socialization. This result was evident across different countries and gender, with minor effects of age on specific goals, and a clear effect of the importance of music in people's lives. Cultural effects were generally small and surfaced mainly in the use of music to obtain a sense of togetherness. Interestingly, culture moderated the use of negatively valenced and nostalgic music for those higher in distress