La morte della Regina riapre il dibattito sulla monarchia, mentre si riaccendono tensioni nei rapporti centro-periferia e il Québec è travolto dallo “Tsunami Caquiste"

In Canada, il quadrimestre settembre-dicembre 2022 è stato segnato dal riaccendersi di tensioni nei rapporti tra la Federazione e alcune Province (Québec, Alberta e Saskatchewan), alimentate dall'instaurazione di precedenti di adozione di emendamenti alla Costituzione unilaterali e di altri atti manifestamente illegittimi, perseguita in modo attivo, consapevole e persino entusiastico dagli organi di indirizzo provinciali, e potenzialmente in grado di aprire una grave crisi costituzionale. Anche il dibattito sul futuro della monarchia, innescato dalla morte della Regina Elisabetta II, è stato condizionato dal cleavage politico-istituzionale che storicamente, in Canada, attraversa il versante dei rapporti tra centro e periferia

A deep-learning framework for metacarpal-head cartilage-thickness estimation in ultrasound rheumatological images

none6openFiorentino, Maria Chiara; Cipolletta, Edoardo; Filippucci, Emilio; Grassi, Walter; Frontoni, Emanuele; Moccia, SaraFiorentino, Maria Chiara; Cipolletta, Edoardo; Filippucci, Emilio; Grassi, Walter; Frontoni, Emanuele; Moccia, Sar

ARCHAEOMETRIC ANALYSES AND RESTORATION OF SILVER JEWELLERY FROM THE PUNIC NECROPOLIS OF THARROS – CAPO SAN MARCO (SARDINIA, ITALY)

The paper reports and discusses data from archaeometric analyses and restoration intervention carried out on an assemblage of silver jewellery pieces from the Punic Southern necropolis of Tharros – Capo San Marco (Sardinia, Italy), a site whose relevance is primarily linked to its stratification, extending from the Nuragic age to the Middle Ages. Belonging to a funerary equipment from a primary incineration tomb, confidently ascribable to 7th-6th century BCE, the jewels were found in a precarious state of conservation, extremely fragmented and, in some cases, held together by a surface alteration layer. High-resolution X-rays CT allowed gaining insights into working techniques and decorative features of the finds under study, whose legibility was severely compromised by the alteration layer. OM and SEM-EDS analyses were also performed, to achieve a more exact characterisation of the alteration products. Obtained data allowed, on the one hand, to establish possible contact with North Africa and, on the other hand, to carry out a meticulous restoration intervention, fully respecting the original integrity of the artefacts despite the precarious state of conservation

Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state.

Transformation of thyroid cells with either K-ras or H-ras viral oncogenes produces cell types with different phenotype and different response to the inhibition of the prenylation pathway by 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyltransferase inhibitors. These inhibitors induce apoptosis in K-ras-transformed FRTL-5 cells (FRTL-5-K-Ras) whereas cell cycle arrest is induced in H-ras-transformed FRTL-5 (FRTL-5-H-Ras). In FRTL-5-K-Ras cells, the product of K-ras gene is implicated in the scavenging of reactive oxygen species (ROS) through the activation of extracellular-signal-regulated kinase (ERK)1/2 kinases. We observed that lovastatin blocked ras activation through inhibition of farnesylation and induced apoptosis, increasing ROS levels through inhibition of ERK1/2 signaling and Mn-SOD expression. Lovastatin-induced apoptosis was due to intracellular ROS increase since both, the antioxidant compound pyrrolidinedithiocarbamate or the SOD-mimetic compound, antagonized apoptosis. Moreover, both p38 mitogen-activated protein kinase and nuclear factor kappaB pathways, activated as a consequence of high ROS levels, are involved in the apoptotic effect, indicating that cell death induced by lovastatin was dependent on oxidative stress. Lovastatin antitumor efficacy in K-ras-dependent thyroid tumors was further confirmed in vivo, proposing a new therapeutic strategy for those tumor diseases that are sustained by an inappropriate K-ras expression

Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study:

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect

Intravenous immunoglobulin therapy in the treatment of the acute phase of chronic idiopathic thrombocytopenic purpura in adults

A prospective, open-label phase III study was carried out to evaluate the efficacy and tolerability of a preparation of virus-inactivated normal human intravenous immunoglobulin. Fifteen adult patients suffering from chronic idiopathic thrombocytopenic purpura (ITP), (basal platelet count <20x109/l), received 0.4 g/kg daily for 5 days. The increase in platelet count, reduction in hemorrhagic events, duration of platelet response, and incidence of adverse events were recorded. Fourteen out of 15 patients achieved a platelet count ?50x109/l (response rate was 93.3%), and only 2 out of 10 patients with positive baseline Rumple-Leed test remained positive after treatment (p =0.0022). Interestingly, a close inverse correlation between platelet counts and haemoglobin levels was observed. No side effects were recorded. This study provides evidence of therapeutic efficacy and the good tolerability of the immunoglobulin preparation we used in this trial, and suggests the role of haemolysis as a mechanism for the increase in platelet count

A Federated Learning Framework for Stenosis Detection

This study explores the use of Federated Learning (FL) for stenosis detection in coronary angiography images (CA). Two heterogeneous datasets from two institutions were considered: Dataset 1 includes 1219 images from 200 patients, which we acquired at the Ospedale Riuniti of Ancona (Italy); Dataset 2 includes 7492 sequential images from 90 patients from a previous study available in the literature. Stenosis detection was performed by using a Faster R-CNN model. In our FL framework, only the weights of the model backbone were shared among the two client institutions, using Federated Averaging (FedAvg) for weight aggregation. We assessed the performance of stenosis detection using Precision (P rec), Recall (Rec), and F1 score (F1). Our results showed that the FL framework does not substantially affects clients 2 performance, which already achieved good performance with local training; for client 1, instead, FL framework increases the performance with respect to local model of +3.76%, +17.21% and +10.80%, respectively, reaching P rec = 73.56, Rec = 67.01 and F1 = 70.13. With such results, we showed that FL may enable multicentric studies relevant to automatic stenosis detection in CA by addressing data heterogeneity from various institutions, while preserving patient privacy

Aurora-A overexpression as an early marker of reflux-related columnar mucosa and Barrett's oesophagus.

Abstract BACKGROUND: The development of oesophageal adenocarcinoma is generally closely associated with the presence of a specialised intestinal-type epithelium such as that found in Barrett's oesophagus (BO). A particular histological condition is when the distal oesophagus showing cardiac and/or fundic mucosa without intestinal metaplasia cannot be defined as 'Barrett's mucosa' [condition that we call 'columnar-lined oesophagus' (CLO)] and up till now, there has been no agreement in literature about the management of this condition. Aurora-A overexpression leads to centrosome amplification, chromosomal instability and aneuploidy in mammalian cells. PATIENTS AND METHODS: A prospective study was carried out on 28 consecutive patients who presented columnar mucosa above the gastro-oesophageal junction (GOJ) at endoscopy. As controls, two more biopsies were obtained, one on the normal-appearing squamous oesophagus above the GOJ, as far as possible from the columnar mucosa (controls A), and one taken 1 cm below the GOJ (controls B). The Aurora-A and p53 expression levels were analysed respectively by Quantitative Real Time PCR and immunohistochemistry. RESULTS: Twelve patients were affected by BO (43%) while the other 16 patients (57%) had a CLO. Nine of 28 (32%) cases were focally positive for p53 immunostaining. All the BO/CLO samples were positive for the Aurora-A transcript with regard to controls. Furthermore, 13 of 28 (46%) cases showed overexpression (above the median for the whole group). CONCLUSION: Due to the low number of cases, we are not at present able to state that statistically significant quantitative differences in Aurora-A messenger RNA expression exist between CLO and BO cases with and without dysplasia and p53-positive immunostaining. Further studies on a larger number of cases with a follow-up period are necessary in order to establish the risk of progression and the correct management of these subjects

Patients with multiple sclerosis: a burden and cost of illness study

Background Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease negatively impacting patients' physical, psychological and social well-being with a significant economic burden. Objectives The study estimates MS burden and cost of illness in Italy from a societal perspective in 2019. Methods Information on the impact of the disease on daily activities, symptoms, employment, resource utilization and the role of caregivers was collected through questionnaires completed by 944 patients and caregivers. Results were stratified according to both disease severity and payer. Mean costs and overall costs were extrapolated from the sample to the Italian MS population considering published distribution of severity. Results The study showed a great impact of the disease on daily and work activities increasing with the disability. The overwhelming burden of fatigue emerged. Mean annual costs were estimated at euro39,307/patient (euro29,676, euro43,464 and euro53,454 in mild, moderate and severe cases, respectively). Direct healthcare costs were the major component (euro21,069), followed by indirect costs (euro15,004). The overall cost of the disease in Italy was euro4.8 billion. The National Healthcare System (NHS) sustained most of the costs (80%), most notably direct healthcare costs, while patients paid almost all non-healthcare expenses. Conclusions This study confirmed that MS carries a substantial burden to patients and society, highlighting the need for awareness of this disease

Relevance of rosette patterns in variants of papillary thyroid carcinoma

IntroductionThe detection of rosette‐like clusters (RLC) of follicular cells in thyroid carcinoma has been reported mostly in the columnar cell variant of papillary thyroid carcinoma (PTC). Despite the fact that diagnosing variants of PTC is no longer encouraged by The Bethesda System for Reporting Thyroid Cytopathology, the identification of cytomorphological features such as RLC linked with these tumours might help reduce possible misinterpretation in thyroid fine needle aspiration (FNA) cytology. We accordingly investigated the potential correlation of architectural patterns including RLC with PTC variants.MethodsWe analysed 225 thyroid FNA cytology cases diagnosed as suspicious for malignancy (SFM) and positive for malignancy (M) over a 1‐year time where all samples had corresponding histology. We also included 150 benign lesions from the same period. The presence of RLC vs similar appearing solid clusters, papillary structures and microfollicles were evaluated. We also performed immunocytochemistry and molecular testing for BRAFV600E.ResultsWe included 100 (44.4%) SFM favouring PTC and 125 (55.6%) M cases with cyto‐histological correlation. On histology, all SFM and M cases showed malignancy including 140 (62.2%) classic PTC and 85 (37.8%) PTC variants. The cytomorphological patterns in all FNA samples included solid (74%), papillary (89%), microfollicular (70%), and pseudo‐RLC morphology (25.7%). We identified only pseudo‐RLC in 33 FNA specimens from PTC variant cases that included tall cell variant (42.4%), hobnail variant (21.2%) and miscellaneous variants (36.3%) of PTC. No definitive RLC were detected in our series. Immunocytochemistry and BRAFV600E were not specifically linked with an RLC pattern.ConclusionsThese findings demonstrate that in our dataset the architectural pattern of RLC was not recognised within PTC variants. However, we did identify a pseudo‐RLC pattern that was observed in association with tall cell variant and hobnail variant cases of PTC.The findings discussed in the present study demonstrate that certain architectural patterns such as rosette‐like clusters (RLC) may be recognized more frequently in specific PTC variants that may be helpful in reducing their misinterpretation. In the series presented, RLCs were observed mostly in association with tall cell and hobnail variants of PTC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163372/2/cyt12885_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163372/1/cyt12885.pd