Role of M3 Muscarinic Acethylcholine Receptor Antibodies as a New Marker in Primary Sjögren Syndrome

Aims: This paper investigates the presence of M3 muscarinic acetylcholine receptor autoantibody present in the serum of patients with primary Sjögren syndrome (pSS). Main methods: We detected the levels of M3mAChR peptide IgG, PGE2, IL-1β in serum of SS patients using the enzyme-linked immune sorbent assay (ELISA). To measure the quantity of nitrite/nitrate, we used Griess reagent system. Key findings: Titres of M3mAChR antibody in sera from SS patients are significantly enhanced compared to healthy subjects (control). The enhancement of these autoantibodies is accompanied by the increase of the levels of PGE2, IL-1β and nitrite/nitrate in serum. Under in vitro conditions, the synthetic human M3 peptide impaires the increment of M3mAChR antibody but not that of nati-Ro/SSA antibody. In positive anti-Ro/SSA antibody patients, the increment of M3mAChR peptide IgG and the measured pro-inflammatory substances is related. Significance: On this basis, anti M3mAChR peptide IgG can be said to act as a modulator of the immune system and to play a role in the host-chronic increment of proinflammatory substances in SS patients with positive Ro/SSA antibody. This association between the antibody and the pathogenesis of SS disease may result in useful predicting SS.Fil: Reina, Silvia Lorena. Universidad Catolica de Las Misiones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pisoni, Cecilia. Centro de Educaciones Médicas e Investigación Clínica ; ArgentinaFil: González Arana, Roberto. Centro de Educaciones Médicas e Investigación Clínica ; ArgentinaFil: Ganzinelli, Sabrina Belen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; ArgentinaFil: Borda, Enri Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentin

Contrastive Language-Image Pre-training for the Italian Language

Recently, multi-modal systems such as CLIP (Contrastive Language-Image Pre-training) were introduced to represent images and texts jointly in the same embedding space. These models are trained on massive amounts of image-caption pairs and show impressive performance on zero-shot image classification. However, their usage is limited to English due to their training data. Training the same model for different languages is non-trivial since the amount of natural data in those might not be sufficient, and automatic translations of original captions might not have sufficient quality, harming performance. In this paper, we present the first CLIP model for the Italian Language (CLIP-Italian), trained on more than 1.4 million image-text pairs. Results show that CLIP-Italian outperforms a multilingual CLIP model on image retrieval and zero-shot classification tasks for the Italian language.1 Sistemi multimodali come CLIP (Contrastive Language-Image Pre-training) sono stati proposti di recente al fine di ottenere rappresentazioni di immagini e testo in uno spazio latente condiviso. Questi modelli sono allenati su enormi quantità di immagini associate alle loro didascalie, e dimostrano abilità eccellenti nell'effettuare classificazioni “zero-shot”. Ciononostante, il loro utilizzo è limitato all'inglese, la lingua utilizzata durante il loro addestramento. Ottenere modelli del genere per altre lingue non è cosa da poco, poiché la quantità di dati a disposizione per queste lingue potrebbe non essere sufficiente e la traduzione automatica delle didascalie inglesi originali potrebbe portare a risultati non soddisfacenti. In questo articolo presentiamo il primo modello CLIP per la lingua italiana (CLIP-Italian), addestrato con più di 1.4 milioni di immagini e rispettive didascalie. I risultati riportati dimostrano l'efficacia di CLIP-Italian per l'estrazione e la classificazione zero-shot in italiano, ottenendo risultati migliori di un modello CLIP multilingue.</p

Contrastive Language-Image Pre-training for the Italian Language

Recently, multi-modal systems such as CLIP (Contrastive Language-Image Pre-training) were introduced to represent images and texts jointly in the same embedding space. These models are trained on massive amounts of image-caption pairs and show impressive performance on zero-shot image classification. However, their usage is limited to English due to their training data. Training the same model for different languages is non-trivial since the amount of natural data in those might not be sufficient, and automatic translations of original captions might not have sufficient quality, harming performance. In this paper, we present the first CLIP model for the Italian Language (CLIP-Italian), trained on more than 1.4 million image-text pairs. Results show that CLIP-Italian outperforms a multilingual CLIP model on image retrieval and zero-shot classification tasks for the Italian language.1 Sistemi multimodali come CLIP (Contrastive Language-Image Pre-training) sono stati proposti di recente al fine di ottenere rappresentazioni di immagini e testo in uno spazio latente condiviso. Questi modelli sono allenati su enormi quantità di immagini associate alle loro didascalie, e dimostrano abilità eccellenti nell'effettuare classificazioni “zero-shot”. Ciononostante, il loro utilizzo è limitato all'inglese, la lingua utilizzata durante il loro addestramento. Ottenere modelli del genere per altre lingue non è cosa da poco, poiché la quantità di dati a disposizione per queste lingue potrebbe non essere sufficiente e la traduzione automatica delle didascalie inglesi originali potrebbe portare a risultati non soddisfacenti. In questo articolo presentiamo il primo modello CLIP per la lingua italiana (CLIP-Italian), addestrato con più di 1.4 milioni di immagini e rispettive didascalie. I risultati riportati dimostrano l'efficacia di CLIP-Italian per l'estrazione e la classificazione zero-shot in italiano, ottenendo risultati migliori di un modello CLIP multilingue.</p

Anti-M3 muscarinic acetylcholine receptor antibodies in systemic lupus erythematosus

Background: Evidences have shown that anti-M3 muscarinic acetylcholine receptor IgG (anti-M3 mAChR IgG) are clinically useful autoantibody that exert a cholinergic pharmacologic effect binding and interacting with M3 mAChR at the level of exocrine gland (salivary and ocular). Aims: The aim of this study was to determine the associations between serum level of anti-M3 mAChR IgG in patients with systemic lupus erythematosus (SLE) and other autoantibodies, serum prostaglandin E2 (PGE2), and clinical manifestations. Methods: Serum autoantibodies against M3 mAChR synthetic peptide were measured by enzyme-linked immuno absorbent assay (ELISA) using, as an antigen, a 25-mer peptide K-R-T-V-P-D-N-Q-C-F-I-Q-F-L-S-N-P-A-V-T-F-G-T-A-I corresponding to the amino acid sequence of the second extracellular loop of the human M3 mAChR. Serum levels of antinuclear antibodies (ANA), anti-Smith (Sm) antibodies, anti-phospholipid (APL) antibodies, and PGE2 were determined by ELISA in patients with SLE. Results: We found significantly enhanced titers of anti-M3 mAChR IgG in sera from SLE patients compared with healthy individuals (control). In addition, serum levels of PGE2 were significantly higher in SLE patients than in control patients and were significantly higher in active than in non-active SLE. No correlation was found with other autoantibodies present in SLE. By contrast, a positive correlation was found between anti-M3 mAChR IgG and PGE2 serum levels in SLE. Conclusions: As anti-M3 mAChR antibodies present in the sera of SLE patients may be another factor in the pathogenesis of this disease, and the increment of PGE2 in the sera of SLE has a modulatory action on the inflammatory process, suggesting that the presence of these autoantibodies against M3 mAChR may contribute to sustained immune deregulation and the strong inflammatory component observed in SLE.Fil: Reina, Silvia Lorena. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pisoni, Cecilia. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Eimon, Alicia. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Carrizo, Carolina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Arana, Roberto. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Changes in Cyclooxygenase-2’s Expression, and PGE2 ’s and 6-keto-PGF1α’s Levels in the Presence of the Muscarinic Acethylcholine Receptor Antibody in Primary Sjögren Syndrome

AbstractAims: This paper investigates the action of M3 muscarinic acetylcholine receptor antibody present in serum from patients with Sjögren syndrome (SS). Methods: Enzyme-linked immunoabsorbent assay (ELISA) was performed in the presence or absence of different enzymatic and specific receptors?antagonist drugs. The levels and the generation of PGE2, 6-keto-PGF1α and cyclic AMP (cAMP) in rat submandibular gland acini?s preparations and in serum from pSS patients were measured in the presence of pSS IgG anti M3 peptide. COX-2 mRNA gene?s expression at Real Time PCR was done in acini?s preparations from rat submandibular gland in the presence of the autoantibodies alone or once previously incubated with different inhibitors.Results: In this study, we show that the activation of M3 mAChR of rat submandibular gland acini?s preparation triggers an increment both in the production of COX-2 mRNA gene?s expression and in the production of PGE2 and 6-keto-PGF1α. These phenomena are accompanied by an increment in the production of cAMP in the acini?s preparation and do not affect COX-1 mRNA?s levels. Both prostanoids are augmented in the sera of pSS patients as compared with healthy individuals.Conclusions: The present study suggests a complex interplay between different factors involved in adaptativa autoimmunity in pSS patients at the level of exocrine glands. The presence of pSS IgG anti M3 peptide, the enhancement of COX-2 mRNA gene?s expression and the increment in the generation of PGE2 and 6-keto-PGF1α abolished by M3 specific cholinergic antagonist, could provide evidence of a link between autoimmunity and the submandibular gland parasympathetic system in the course of Sjögren?s syndrome. This evidence is further supported by an increment in the production of AMP cyclic nucleotide (cAMP), and the subsequent induction of desensitization, internalization and/or intracellular degradation of the glandular M3 mAChR displayed by the cholinergic autoantibody. All of these statements cited above, are responsible for xerostomy, xerophthalmia and other parasympathetic symptoms observed in SS patients.Fil: Reina, Silvia Lorena. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pisoni, Cecilia. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Eimon, Alicia. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Carrizo, Carolina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Ganzinelli, Sabrina Belen. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arana, Roberto. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Borda, Enri Santiago. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Archeologia delle alte quote sulla montagna veneta: la campagna di ricognizione di superficie 2019 a Recoaro Terme (Vicenza)

In this paper we present the preliminary results of the 2019 field survey conducted in the framework of the project \u201cBeyond the border. Study and enhancement of the highlands between Veneto and Trentino\u201d. The aim of this overarching project, which applies a multidisciplinary approach, is threefold: to detect in this mountain landscape the main activity areas and reconstruct possible connections between them; to analyse the long-term relationships between Trentino and Prealpine Veneto from prehistory to the present day; and to study the evolving function of this frontier area during periods of conflict/interaction. Several methods were employed to shed light on the above-mentioned research aims: field-walking survey, analysis of aerial photos, ethnographic and archival research, GIS-based landscape analysis and predictive modelling, and LiDAR data for feature detection in wooded areas. The combined use of all these approaches allowed us to identify long-term exploitation activities, which are documented also by both the ethnographic and archaeological data. The major periods of conflict in these areas are also highlighted in the archaeological record. The 2019-survey campaign opens up new research directions such as the future excavation of Bronze Age occupation zones; network and connectivity analysis between Prealpine Veneto and Trentino; hillforts and their interaction with the highlands

Clinical Features and Outcome of 79 Dogs With Digital Squamous Cell Carcinoma Undergoing Treatment: A SIONCOV Observational Study

In dogs, digit squamous cell carcinoma (SCC) is uncommon. Clinical signs are frequently underestimated, leading to a diagnostic delay. The purpose of this retrospective study was to report our experience regarding the clinical presentation, diagnostic work-up, treatment and outcome of 79 client-owned dogs with SCC of the digit. The greatest majority (84.8%) of dogs was dark-coated. Schnauzers represented approximately one third of the study population, and had a poorer outcome compared with other breeds. The majority of SCCs occurred in the front limbs (61%), and bone lysis was frequently observed (92.4%). Approximately 9% of dogs had involvement of multiple digits, and this was associated with a shorter time to progression (TTP; P = 0.047). Similarly, a duration of clinical signs &gt;90 days was associated with a shorter TTP (P = 0.02). Regional lymph node metastases were documented in 17.7% of dogs at admission and were significantly associated with tumor-related death (P &lt; 0.001). At presentation, none of the dogs had evidence of distant metastasis. Digit amputation achieved adequate local tumor control in the majority of cases. Adjuvant chemotherapy and radiation therapy were carried out in 21.5% of cases, with uncertain benefit. Due to the relatively non-aggressive clinical behavior of digit SCC, chemotherapy should only be offered in the case of metastatic disease. Approximately one fourth of dogs developed de novo SCCs during the follow-up. Careful examination of the digits should be encouraged in breeds considered at high risk and in dogs with a previous history of digital SCC

Clinical Features and Outcome of 79 Dogs With Digital Squamous Cell Carcinoma Undergoing Treatment: A SIONCOV Observational Study

In dogs, digit squamous cell carcinoma (SCC) is uncommon. Clinical signs are frequently underestimated, leading to a diagnostic delay. The purpose of this retrospective study was to report our experience regarding the clinical presentation, diagnostic work-up, treatment and outcome of 79 client-owned dogs with SCC of the digit. The greatest majority (84.8%) of dogs was dark-coated. Schnauzers represented approximately one third of the study population, and had a poorer outcome compared with other breeds. The majority of SCCs occurred in the front limbs (61%), and bone lysis was frequently observed (92.4%). Approximately 9% of dogs had involvement of multiple digits, and this was associated with a shorter time to progression (TTP; P = 0.047). Similarly, a duration of clinical signs &gt;90 days was associated with a shorter TTP (P = 0.02). Regional lymph node metastases were documented in 17.7% of dogs at admission and were significantly associated with tumor-related death (P &lt; 0.001). At presentation, none of the dogs had evidence of distant metastasis. Digit amputation achieved adequate local tumor control in the majority of cases. Adjuvant chemotherapy and radiation therapy were carried out in 21.5% of cases, with uncertain benefit. Due to the relatively non-aggressive clinical behavior of digit SCC, chemotherapy should only be offered in the case of metastatic disease. Approximately one fourth of dogs developed de novo SCCs during the follow-up. Careful examination of the digits should be encouraged in breeds considered at high risk and in dogs with a previous history of digital SCC

ARTEFACTS: How do we want to deal with the future of our one and only planet?

The European Commission’s Science and Knowledge Service, the Joint Research Centre (JRC), decided to try working hand-in-hand with leading European science centres and museums. Behind this decision was the idea that the JRC could better support EU Institutions in engaging with the European public. The fact that European Union policies are firmly based on scientific evidence is a strong message which the JRC is uniquely able to illustrate. Such a collaboration would not only provide a platform to explain the benefits of EU policies to our daily lives but also provide an opportunity for European citizens to engage by taking a more active part in the EU policy making process for the future. A PILOT PROGRAMME To test the idea, the JRC launched an experimental programme to work with science museums: a perfect partner for three compelling reasons. Firstly, they attract a large and growing number of visitors. Leading science museums in Europe have typically 500 000 visitors per year. Furthermore, they are based in large European cities and attract local visitors as well as tourists from across Europe and beyond. The second reason for working with museums is that they have mastered the art of how to communicate key elements of sophisticated arguments across to the public and making complex topics of public interest readily accessible. That is a high-value added skill and a crucial part of the valorisation of public-funded research, never to be underestimated. Finally museums are, at present, undergoing something of a renaissance. Museums today are vibrant environments offering new techniques and technologies to both inform and entertain, and attract visitors of all demographics.JRC.H.2-Knowledge Management Methodologies, Communities and Disseminatio