Overcoming the Limits of EMU Through Covid? Next Generation EU Against the Unaddressed Needs for Ambitious Structural Reform

The article considers the long-standing limits of the Economic and Monetary Union (EMU) through the lenses of Next Generation EU (NGEU) pandemic response evidencing how Covid-19 exacerbated EMU shortcomings are (not) overcome. We evaluate whether NGEU is only a palliative stop-gap fix to structural problems and how for Covid-19 to be considered as a breaking point for EU economic governance permanent ambitious (Treaty) reform is an essential and so far not uncontested step. A qualitative systematic review of weaknesses of EMU and proposed reforms informs a scoreboard evaluation of NGEU. Results confirm that while the symmetric crisis allowed suspending risk-sharing and solidarity vetoes, deep structural asymmetries and unfitness of (intergovernmental) decision-making cannot be addressed through NGEU temporary emergency mechanism. Hence Covid-19 so far cannot be narrated as sparking a revolutionary deviation from the architecture and guiding principle of the supranational fiscal framework. At the same time, the pandemic opened a (short-lived) window of opportunity for completing the EMU, requiring permanent structural institutional (Treaty) reform. A timely finding – grounded in copious extant literature on the EMU – highlighting the high stakes of the ongoing Conference of the future of Europe, whose success can only materialise through an ambitious (federal) agenda

Zinc transporter 8 and MAP3865c homologous epitopes are recognized at T1D onset in Sardinian children

Our group has recently demonstrated that Mycobacterium avium subspecies paratuberculosis (MAP) infection significantly associates with T1D in Sardinian adult patients. Due to the potential role played by MAP in T1D pathogenesis, it is relevant to better characterize the prevalence of anti-MAP antibodies (Abs) in the Sardinian population, studying newly diagnosed T1D children. Therefore, we investigated the seroreactivity against epitopes derived from the ZnT8 autoantigen involved in children at T1D onset and their homologous sequences of the MAP3865c protein. Moreover, sera from all individuals were tested for the presence of Abs against: the corresponding ZnT8 C-terminal region, the MAP specific protein MptD, the T1D autoantigen GAD65 and the T1D unrelated Acetylcholine Receptor. The novel MAP3865c281–287 epitope emerges here as the major C-terminal epitope recognized. Intriguingly ZnT8186–194 immunodominant peptide was cross-reactive with the homologous sequences MAP3865c133–141, strengthening the hypothesis that MAP could be an environmental trigger of T1D through a molecular mimicry mechanism. All eight epitopes were recognized by circulating Abs in T1D children in comparison to healthy controls, suggesting that these Abs could be biomarkers of T1D. It would be relevant to investigate larger cohorts of children, followed over time, to elucidate whether Ab titers against these MAP/Znt8 epitopes wane after diagnosis

Cluster of legionnaires’ disease in an Italian prison

Background: Legionella pneumophila (Lp) is the most common etiologic agent causing Legionnaires’ Disease (LD). Water systems offer the best growth conditions for Lp and support its spread by producing aerosols. From 2015 to 2017, the Regional Reference Laboratory of Clinical and Environmental Surveillance of Legionellosis of Palermo monitored the presence of Lp in nine prisons in Western Sicily. During this investigation, we compared Lp isolates from environmental samples in a prison located in Palermo with isolates from two prisoners in the same prison. Methods: We collected 93 water samples from nine Sicilian prisons and the bronchoalveolar lavages (BALs) of two prisoners considered cases of LD. These samples were processed following the procedures described in the Italian Guidelines for the Prevention and Control of Legionellosis of 2015. Then, genotyping was performed on 19 Lp colonies (17 from water samples and 2 from clinical samples) using the Sequence-Based Typing (SBT) method, according to European Study Group for Legionella Infections (ESGLI) protocols. Results: Lp serogroup (sg) 6 was the most prevalent serogroup isolated from the prisons analyzed (40%), followed by Lp sg 1 (16%). Most of all, in four penitentiary institutions, we detected a high concentration of Lp >104 Colony Forming Unit/Liter (CFU/L). The environmental molecular investigation found the following Sequence Types (STs) in Lp sg 6: ST 93, ST 292, ST 461, ST 728, ST 1317 and ST 1362, while most of the isolates in sg 1 belonged to ST 1. We also found a new ST that has since been assigned the number 2451 in the ESGLI-SBT database. From the several Lp sg 1 colonies isolated from the two BALs, we identified ST 2451. Conclusions: In this article, we described the results obtained from environmental and epidemiological investigations of Lp isolated from prisons in Western Sicily. Furthermore, we reported the first cluster of Legionnaires’ in an Italian prison and the molecular typing of Lp sg 1 from one prison’s water system and two BALs, identified the source of the contamination, and discovered a new ST

Levodopa-Induced Dyskinesias and Dyskinesias-Reduced-Self-Awareness in Parkinson’s Disease: A Neurocognitive Approach

Levodopa-induced dyskinesias are one of the most common disabling motor complications in advanced Parkinson’s disease. The subjective perception of motor impairment is a clinical phenomenon that needs to be adequately analyzed. Indeed, the determination of patient dyskinesias-reduced-self-awareness (DRSA) and of its relationship to daily dysfunction is an important aspect of the debate on the gold standard for treatment. As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in DRSA, we analyzed metacognitive abilities related to action monitoring and other factors, such as response-inhibition and “Theory of Mind,” which represent a novel explanation of the phenomenon. Moreover, we investigated whether and how a dysfunction in action monitoring related to the cingulo-frontal-ventral striatal circuit would be associated with DRSA using an event-related Go-NoGo fMRI experiment. Our findings suggest the presence of executive dysfunctions in DRSA pathogenesis, with a key leading role played by the cingulo-frontal network as part of a functionally impaired response-inhibition network

Mixed Reality Environment and High-Dimensional Continuification Control for Swarm Robotics

A significant challenge in control theory and technology is to devise agile and less resource-intensive experiments for evaluating the performance and feasibility of control algorithms for the collective coordination of large-scale complex systems. Many new methodologies are based on macroscopic representations of the emerging system behavior, and can be easily validated only through numerical simulations, because of the inherent hurdle of developing full scale experimental platforms. In this paper, we introduce a novel hybrid mixed reality set-up for testing swarm robotics techniques, focusing on the collective motion of robotic swarms. This hybrid apparatus combines both real differential drive robots and virtual agents to create a heterogeneous swarm of tunable size. We validate the methodology by extending to higher dimensions, and investigating experimentally, continuification-based control methods for swarms. Our study demonstrates the versatility and effectiveness of the platform for conducting large-scale swarm robotics experiments. Also, it contributes new theoretical insights into control algorithms exploiting continuification approaches

Clinical significance of rare serum autoantibodies in rheumatic diseases: a systematic literature review

The identification of serum autoantibodies is central in the diagnosis of systemic autoimmune rheumatic disease (SARD), and an increasing number of specificities have been detected in the past years. This allows an early diagnosis in the active phases of diseases, with the identification of specific disease subsets that may ultimately improve the disease outcomes. Thanks to the use of old and new laboratory techniques that are becoming increasingly available worldwide, the number of rheumatic patients with a specific autoantibody is increasing and this is improving also our knowledge of disease trigger mechanisms. The paradigmatic example is the plethora of serum autoantibodies described in polymyositis and dermatomyositis, coined myositis-specific antibodies (MSA) which include antibodies directed against tRNA synthetases, anti-SRP, anti-Mi-2, and anti-TIF-1γ and can discriminate disease subtypes, particularly when associated with the risk of cancer. As a further example, anti-HMGCR antibodies have been reported in several studies in association with necrotizing autoimmune myositis that may follow statin use. To clarify the current knowledge on these rare specificities, we performed a systematic literature review. We focused on the main features associated to specific autoantibodies that are rarely identified in rheumatic disease, to increase the awareness and scientific knowledge on these autoantibodies in different ethnic groups worldwide.Fil: Ceribelli, Angela. Humanitas Research Hospital; Italia. Università degli Studi di Milano; ItaliaFil: Isailovic, Natasa. Humanitas Research Hospital; ItaliaFil: De Santis, Maria. Humanitas Research Hospital; ItaliaFil: Generali, Elena. Humanitas Research Hospital; ItaliaFil: Gorlino, Carolina Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Humanitas Research Hospital; ItaliaFil: Palermo, Bianca. Humanitas Research Hospital; ItaliaFil: Selmi, Carlo. Università degli Studi di Milano; Italia. Humanitas Research Hospital; Itali

NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest.

Notch dysregulation has been implicated in numerous tumors, including triple-negative breast cancer (TNBC), which is the breast cancer subtype with the worst clinical outcome. However, the importance of individual receptors in TNBC and their specific mechanism of action remain to be elucidated, even if recent findings suggested a specific role of activated-Notch3 in a subset of TNBCs. Epidermal growth factor receptor (EGFR) is overexpressed in TNBCs but the use of anti-EGFR agents (including tyrosine kinase inhibitors, TKIs) has not been approved for the treatment of these patients, as clinical trials have shown disappointing results. Resistance to EGFR blockers is commonly reported. Here we show that Notch3-specific inhibition increases TNBC sensitivity to the TKI-gefitinib in TNBC-resistant cells. Mechanistically, we demonstrate that Notch3 is able to regulate the activated EGFR membrane localization into lipid rafts microdomains, as Notch3 inhibition, such as rafts depletion, induces the EGFR internalization and its intracellular arrest, without involving receptor degradation. Interestingly, these events are associated with the EGFR tyrosine dephosphorylation at Y1173 residue (but not at Y1068) by the protein tyrosine phosphatase H1 (PTPH1), thus suggesting its possible involvement in the observed Notch3-dependent TNBC sensitivity response to gefitinib. Consistent with this notion, a nuclear localization defect of phospho-EGFR is observed after combined blockade of EGFR and Notch3, which results in a decreased TNBC cell survival. Notably, we observed a significant correlation between EGFR and NOTCH3 expression levels by in silico gene expression and immunohistochemical analysis of human TNBC primary samples. Our findings strongly suggest that combined therapies of TKI-gefitinib with Notch3-specific suppression may be exploited as a drug combination advantage in TNBC treatment

Annurca apple (M. pumila Miller cv Annurca) extracts act against stress and ageing in S. cerevisiae yeast cells

During the past years, a number of studies have demonstrated the positive effect of apple on ageing and different diseases such as cancer, degenerative and cardiovascular diseases. The unicellular yeast Saccharomyces cerevisiae represents a simple eukaryotic model to study the effects of different compounds on lifespan. We previously demonstrated that apple extracts have anti-ageing effects in this organism because of their antioxidant properties. In particular, the effect is related to the presence in this fruit of polyphenols, which give a large contribution to the antioxidant activity of apples