25 research outputs found
Interplay between inflammation, autoimmunity and regeneration in the NOD mouse model of type 1 diabetes and Sjogren’s Syndrome.
PhDA continuous process of tissue remodelling and regeneration is a fundamental feature of the
homeostatic response of the target organ of several autoimmune diseases. In type 1 diabetes (T1D)
the β cell mass is in a constant process of death and renewal in order to regenerate the islets
damaged by the autoimmune process. The relationship linking inflammation and regeneration
during autoimmunity remains elusive. Reg genes, a multigene family discovered using cDNA
libraries derived from rat regenerating islets, have been suggested to play an important role in
epithelial regeneration not only in the pancreas but also in the salivary glands (SG) of Sjogren’s
Syndrome (SS) during autoimmune sialoadenitis.
Both in patients and animal models of T1D and SS, the chronic inflammatory/autoimmune process
is heterogeneous and display high immunological variability. In particular, in a sizeable subset of
cases, inflammatory lesions display ectopic lymphoid structures (ELS) characterised by T/B cell
segregation, follicular dendritic cells networks and differentiation of germinal center B cells.
However, there is limited evidence on the cellular and molecular mechanisms underlying ELS
formation and their contribution to autoimmunity in the pancreas during autoimmune insulitis and
in SG during autoimmune sialoadenitis. In this PhD project, I used the NOD mouse model of T1D
and SS in order to investigate i) the cellular and molecular mechanisms regulating ELS formation,
ii) the functionality of ELS in supporting in situ autoreactive B cell differentiation and iii) the
relationship between formation of ELS and the expression of REG genes.
In this work I showed that ELS formation was preceded by local up-regulation of lymphotoxins
(LTαβ) and lymphoid chemokines CXCL13 and CCL19 and that, once formed, ELS were fully
functional in promoting autoreactive B cell activation. Importantly, inhibition of the LT-β pathway
prevented the formation of ELS and B cell autoimmunity. Finally, I showed that the expression
pattern of Reg genes was strictly related to the development of inflammatory infiltrates in NOD
7
mice and that Reg proteins were target of the autoimmune process itself, as shown by the
development of anti-Reg1 antibodies in patients with T1D. Overall, these results suggest that the
processes of destruction and regeneration occurring in chronic autoimmune/inflammatory diseases
are strongly interdependent whereby autoimmunity may be further enhanced by the attempt to
regenerate
CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland infiltrates: fractalkine contribution to lymphoid neogenesis in Sjogren's syndrome
Methods. We assessed the presence of CX3CL1 protein in sera by ELISA in 21 patients with primary SS, 11 patients with Sicca syndrome (Sicca), 20 RA patients and 10 blood donors. Histological evaluation was performed on sequential sections of salivary gland tissue. Using TaqMan RT-PCR we studied CX3CL1 and CX3CR1 mRNA expression in salivary gland tissues from a molecular point of view. Results. Increased serum levels of CX3CL1 protein were observed in SS patients compared with controls (P < 0.0001) and in RA patients compared with controls (P < 0.0001), but no difference was found between Sicca patients and controls (P = 0.22). We identified histologically the cells expressing CX3CL1 and CX3CR1 in salivary glands of SS patients and we localized the molecule within tertiary lymphoid structures. Finally, the mRNA levels of the CK and its receptor were up-regulated in SS salivary glands. Conclusion. We believe that our findings point to the need for future studies on CX3CL1 and CX3CR1 proteins as contributors to the formation of ectopic GCs and possibly as a new tool in the evaluation and diagnosis of SS
La tutela delle innovazioni in campo vegetale
La tesi ha ad oggetto le forme di tutela dei diritti di proprietà industriale sulle invenzioni aventi ad oggetto piante. La prima parte del lavoro è dedicata ad un’analisi delle linee evolutive degli strumenti specifici di protezione delle nuove varietà vegetali introdotti, dapprima, nell’ordinamento giuridico statunitense e, qualche tempo dopo, in quelli dei Paesi aderenti alla Convenzione UPOV.
L’autore pone a confronto le suddette discipline ad hoc con la normativa brevettuale classica, evidenziandone le differenze sia sul piano dei rispettivi requisiti d’accesso che su quello del contenuto e della portata della tutela.
Viene, dunque, valutato l’impatto prodotto dall’avvento delle moderne biotecnologie sui sistemi normativi vigenti in Europa e negli Stati Uniti in materia di protezione dell’innovazione conseguita in campo agricolo.
Attraverso lo studio dei principali arresti giurisprudenziali e delle iniziative legislative succedutisi negli ultimi anni, vengono delineati i tratti caratteristici degli approcci adottati, rispettivamente, oltre-Atlantico e nel vecchio continente al fine di fornire risposta alle questioni determinate dalla rivoluzione biotecnologica, con particolare riguardo ai problemi di interfaccia fra tutela varietale e tutela brevettuale che quest’ultima ha determinato.
L’autore ritiene che le vie seguite negli Stati Uniti ed in Europa, per quanto diverse tra loro sul piano formale, non siano poi così distanti nella sostanza e, de jure condendo, suggerisce di ridefinire in Europa le interrelazioni fra tutela varietale e tutela brevettuale, abrogando il divieto di brevettazione delle nuove varietà vegetali, vero elemento differenziale fra il contesto normativo europeo e quello statunitense.Intellectual property rights on plant-related inventions are the subject matter of this thesis.
In the first part of this work, the author analyzes the evolution of the specific means of protection for new plant varieties first introduced in the United States of America and then in the member States of the UPOV Convention.
The author makes a comparison between these ad hoc means of protection and the patent protection, by pointing out the differences in respect to the conditions for protection and the scope of protection.
After that, an assessment of the impact of modern biotechnology on the existent European and American plant-related invention systems of protection is made.
The author investigates the approaches which were chosen in Europe and in the United States of America in order to address the issues related to the biotechnological revolution, with particular focus on the interface problems between plant variety protection and patent protection, by means of a study of the principal case law and regulatory interventions adopted during the last years.
The author believes that American and European approaches are not so different in substance and, de jure condendo, suggests redefining the relationship between plant variety protection and patent protection in Europe through the elimination of the ban on patent protection for plant varieties, which is the real differential factor between European and American normative contexts
EVALUATION OF WATER QUALITY IN FONTANILI SPRINGS LOCATED IN AGRICULTURAL AREAS IN NORTH ITALY BY MEASURING THE BEHAVIORAL RESPONSES OF INDIGENOUS AMPHIPODS
Prezentowana tutaj praca to charakterystyka Fontanili - źródeł typowych dla regionu Lombardii (północne Włochy) jako ekosystemow zwiazanych z wodami gruntowymi i podziemnymi w kontekscie projektu GENESIS o wodach podziemnych i zwiazanych z nimi ekosytemach (Projekt Europejski finansowany z Siodmego Programu Ramowego Unii Europejskiej).
Celem niniejszej pracy doktorskiej było:
- Scharakteryzować fontanili jako ekosystemy na podstawie dostępnej wiedzy naukowej;
- Określić reakcje ekotoksykologiczne rodzimych gatunków Amphipoda na zanieczyszcenia pochodzenia rolnego w fontanili oraz zbadanie czy zastosowana metoda może służyć jako bioindykator zanieczyszczenia w ekosystemów fontanili.
Przedstawione cele są adresowane w następujących sekcjach. Sekcja 3 charakteryzuje ekosystemy fontanili na podstawie dostępnej wiedzy naukowej. Rozdział 4 jest przeglądem wskaźników biologicznych, do oceny jakości wód z uwzględnieniem bezkręgowców. Rozdział 5 przedstawia wyniki badań terenowych w wybranych fontanili z wykorzystaniem biologicznycznej metody in situ z uzyciem rodzimego gatunku z rzedu obunogow (Amphipoda) – Echinogammarus stammeri. Rozdziały 6 i 7 relacjonuja eksperymenty laboratoryjne przeprowadzone na rodzimych gatunkach Amphipoda w celu sprawdzenia ich reakcji na najczęściej wykrywane zanieczyszczenia w fontanili.
Oprócz prac prowadzonych we Włoszech, autor wraz z Sarah Joseffson z Wydziału Nauk Wodnych i Oceny, Szwedzki Uniwersytet Nauk Rolniczych w Uppsali, Szwecja przeprowadziła badanie na temat "Transferu trwałych zanieczyszczeń organicznych (POPs) z ekosystemow wodnych do ekosystemow lądowych z uwzglednieniem owadów jako wektorow ". Opis i wstępne wyniki tej pracy można znaleźć w Załączniku I.Il lavoro qui presentato è incentrato sulla caratterizzazione dei Fontanili - risorgive semi-natural1 comuni della regione Lombardia (Nord Italia), GDES rilevanti per il progetto GENESIS sulle acque sotterranee (progetto europeo finanziato nell'ambito del 7th Framework Programme). Gli obiettivi di questo lavoro di dottorato sono stati:
- Caratterizzare gli ecosistemi Fontanili sulla base delle conoscenze scientifiche disponibili;
- Individuare le risposte ecotossicologiche di un indigeno specie bentoniche macroinvertebrati alla contaminazione agricola attraverso la sperimentazione in Fontanili per verificare se il metodo applicato può servire come bioindicatore della contaminazione negli ecosistemi Fontanili.
Gli obiettivi indicati sono affrontati nelle sezioni seguenti. Sezione 3 caratterizza gli ecosistemi Fontanili sulla base delle conoscenze scientifiche disponibili. La sezione 4 è una rivista di indicatori biologici per la valutazione della qualità delle acque con particolare attenzione alla macroinvertebrati. La sezione 5 presenta i risultati degli studi su Fontanili selezionati con l'uso di un test biologico in situ di alimentazione con un anfipode indigena Echinogammarus stammeri. I capitoli 6 e 7 sono esperimenti di laboratorio condotti per misurare le risposte delle anfipodi di inquinanti agricoli rilevati nei Fontanili studiati.
A parte il lavoro condotto in Italia, l'autore insieme a Sarah Joseffson dal Dipartimento di Scienze acquatica e Valutazione, Università Svedese di Scienze Agrarie a Uppsala, in Svezia eseguito uno studio "Trasferimento di inquinanti organici persistenti da acquatico a ambienti terrestri con insetti acquatici come vettori" nel 2012. La descrizione e preliminari risultati di questo lavoro di studio possono essere trovati nell'appendice I.The work presented here is focused on characterization of fontanili - semi-natural1 springs common in the Lombardy region (North Italy), relevant groundwater dependent ecosystems for the GENESIS project on groudwater systems (European project funded under the 7th Framework Programme).
The objectives of this PhD work were:
- to characterize the fontanili ecosystems based on the available scientific knowledge;
- to identify ecotoxicological responses of an indigenous macroinvertebrate benthic species to agricultural contamination through experimentation in fontanili ecosystems This will test if the applied method can serve as a bioindicator of contamination in the fontanili ecosystems.
The mentioned objectives are addressed in the following sections. Section 3 characterizes the fontanili ecosystems based on the available scientific knowledge. Section 4 is an overview of biological indicators as water quality assessment with focus on macroinvertebrates. Section 5 presents the results of field studies on selected fontanili sites with the use of an in situ feeding bioassay with an indigenous amphipod Echinogammarus stammeri. Chapters 6 and 7 are laboratory experiments conducted to measure the responses of the amphipods to commonly detected agricultural pollutants in the studied fontanili.
Apart from the work conducted in Italy, the author together with Sarah Joseffson from the Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences in Uppsala, Sweden performed a study “Transfer of persistent organic pollutants from aquatic to terrestrial environments with aquatic insects as vectors” in 2012. The description and preliminary results of this study work can be found in Appendix I
Online extreme challenges putting children at risk: what we know to date
INTRODUCTION: Extreme online challenges consist in taking part in challenges proposed on web and sharing the results in videos posted on social media. The use of social networks is widespread among the very young, giving easy access to potentially dangerous content with consequences on health.
EVIDENCE ACQUISITION: The aim of this literature review is to describe the most common challenges involving children and adolescents over the last 20 years. We focused on participants features (such as age, sex and psychological background) and health implications. The review included research articles and reviews published between 2000 and 2021. We used Pubmed, Scopus and Web of science as search engines.
EVIDENCE SYNTHESIS: Many types of online challenges emerged from the analysis of the literature. The most common challenges are those that lead to self-harm, which involve acts at risk of choking and challenges that potentially lead to suicide and ingestion of substances. The extreme challenge phenomenon is a public health issue that affects a vulnerable population, as it is young and susceptible to peer pressure influence. Participants often showed problematic personality traits, making them more likely to get involved in these behaviors.
CONCLUSIONS: It is necessary for parents, teachers and health workers to be aware of the spread of the online challenges, to improve prevention interventions in the age groups involved
Vaccination Open Day: A Cross-Sectional Study on the 2023 Experience in Lombardy Region, Italy
Background: Vaccination is a highly effective tool for controlling infectious diseases, particularly in populations at high risk of contagion due to clinical conditions or occupational exposure, such as healthcare workers. The purpose of this study is to present the open day event that marked the beginning of the influenza and anti-COVID-19 vaccination campaign in the Lombardy region and to describe the experience of an Istituto di Ricovero e Cura a Carattere Scientifico in Milan. Methods: During the vaccination open day, eligible individuals received free vaccinations for influenza, COVID-19, pneumococcal disease, and shingles, as provided by the Lombardy Agenzia per la Tutela della Salute. In celebration of the centenary of the Università degli Studi di Milano, the Fondazione Ca’Granda Ospedale Policlinico, a contracted hospital of the university, created a special electronic diary for a total of 150 individuals, equally divided between children aged 2–6, pregnant women, and university staff. Results: At the regional level, a total of 6634 influenza vaccines, 2055 anti-COVID-19 vaccines, 108 anti-pneumococcal vaccines, and 37 anti-zoster vaccines were administered. A total of 3134 (47.3%) influenza vaccines, 1151 (56%) anti-COVID-19 vaccines, and 77 (62%) anti-pneumococcal vaccines, were given to individuals aged 60–79. No differences were observed between the total number of male and female vaccinees (1017 and 1038, respectively), who received the anti-COVID-19 vaccine. At the Policlinico Foundation, out of 150 available booking slots, 154 vaccines were administered, including 117 influenza vaccines. Conclusions: The establishment of vaccine open days is a beneficial way to increase vaccine compliance. Co-administration of little-known vaccinations outside of healthcare settings could also be a useful tool
The British Society for Rheumatology guideline for the management of adults with primary Sjögren’s Syndrome
This is a pre-copyedited, author-produced version of an article accepted for publication in Rheumatology following peer review. The version of record, Price, E. J., et al. (2017). "The British Society for Rheumatology guideline for the management of adults with primary Sjögren’s Syndrome." Rheumatology 56(10): e24-e48. is available online at:https://doi.org/10.1093/rheumatology/kex16
La tutela delle innovazioni in campo vegetale
La tesi ha ad oggetto le forme di tutela dei diritti di proprietà industriale sulle invenzioni aventi ad oggetto piante. La prima parte del lavoro è dedicata ad un’analisi delle linee evolutive degli strumenti specifici di protezione delle nuove varietà vegetali introdotti, dapprima, nell’ordinamento giuridico statunitense e, qualche tempo dopo, in quelli dei Paesi aderenti alla Convenzione UPOV.
L’autore pone a confronto le suddette discipline ad hoc con la normativa brevettuale classica, evidenziandone le differenze sia sul piano dei rispettivi requisiti d’accesso che su quello del contenuto e della portata della tutela.
Viene, dunque, valutato l’impatto prodotto dall’avvento delle moderne biotecnologie sui sistemi normativi vigenti in Europa e negli Stati Uniti in materia di protezione dell’innovazione conseguita in campo agricolo.
Attraverso lo studio dei principali arresti giurisprudenziali e delle iniziative legislative succedutisi negli ultimi anni, vengono delineati i tratti caratteristici degli approcci adottati, rispettivamente, oltre-Atlantico e nel vecchio continente al fine di fornire risposta alle questioni determinate dalla rivoluzione biotecnologica, con particolare riguardo ai problemi di interfaccia fra tutela varietale e tutela brevettuale che quest’ultima ha determinato.
L’autore ritiene che le vie seguite negli Stati Uniti ed in Europa, per quanto diverse tra loro sul piano formale, non siano poi così distanti nella sostanza e, de jure condendo, suggerisce di ridefinire in Europa le interrelazioni fra tutela varietale e tutela brevettuale, abrogando il divieto di brevettazione delle nuove varietà vegetali, vero elemento differenziale fra il contesto normativo europeo e quello statunitense.Intellectual property rights on plant-related inventions are the subject matter of this thesis.
In the first part of this work, the author analyzes the evolution of the specific means of protection for new plant varieties first introduced in the United States of America and then in the member States of the UPOV Convention.
The author makes a comparison between these ad hoc means of protection and the patent protection, by pointing out the differences in respect to the conditions for protection and the scope of protection.
After that, an assessment of the impact of modern biotechnology on the existent European and American plant-related invention systems of protection is made.
The author investigates the approaches which were chosen in Europe and in the United States of America in order to address the issues related to the biotechnological revolution, with particular focus on the interface problems between plant variety protection and patent protection, by means of a study of the principal case law and regulatory interventions adopted during the last years.
The author believes that American and European approaches are not so different in substance and, de jure condendo, suggests redefining the relationship between plant variety protection and patent protection in Europe through the elimination of the ban on patent protection for plant varieties, which is the real differential factor between European and American normative contexts
Climate Change Perception and Mental Health. Results from a Systematic Review of the Literature
Climate change is one of the main global challenges and influences various aspects of human health. Numerous studies have indeed demonstrated an association between extreme climate-related events and physical and mental health outcomes, but little is still known about the association between the perception/awareness of climate change and mental health. In accordance with the PRISMA 2020 guidelines, a search was conducted on PubMed and Scopus. The protocol was registered on PROSPERO. The included studies were original observational studies published in English, reporting the association between the perception/awareness of climate change and mental health. A total of 3018 articles were identified. A total of 10 observational studies were included. The period covered in the included studies ranged between 2012 and 2022. Climate change perception is consistently associated with adverse mental health effects across different types of estimates. In particular, the studies identified an association between a higher level of perception/awareness of climate change and depression, anxiety, eco-anxiety, stress, adjustment disorder, substance use, dysphoria, and even thoughts of suicide. Qualitative data underscore the impact on daily activities, contributing to feelings of loss and suicidal ideation. Moreover, climate change perception correlates with lower well-being and resilience. The association between awareness of climate change and mental health is a complex and still poorly explored phenomenon. The main limitations are the high heterogeneity in terms of exposure assessment and data reporting, which hinders quantitative analysis. These results show that climate change perception impacts mental health. Better understanding the phenomenon represents an opportunity to inform public health interventions that promote mental well-being
Blue eyes as a risk factor for type 1 diabetes
Background A high frequency of blue eyes and fair skin are reported in northern European Caucasians with type 1 diabetes (T1D). Also there is an inverse relationship between latitude and T1D incidence. We determined whether iris colour and skin pigmentation are risk factors in a Caucasian population living in two Mediterranean regions located at the same latitude with higher ultraviolet B irradiance, but with different T1D incidence. Methods We studied iris colour in 281 consecutive subjects with T1D and 298 controls. Skin type was evaluated by melanin quantification. Results In Lazio, blue eyes and fair skin type are significantly more common in T1D subjects than in controls (21 versus 9%, p = 0.002; 50 versus 35%, p < 0.001, respectively). In Sardinia, the frequency of blue eyes in T1D subjects is twice that in controls (5.8 versus 2.6% and significantly higher when compared to the expected calculated frequency in the entire population). By logistic regression analysis, only blue eyes are independent and significant predictors of T1D [odds ratio for blue eyes = 2.2; 95% confidence interval (1.1-4.4), p = 0.019]. Conclusions As previously shown in a Caucasian population from northern Europe, blue eyes and a trend for fair skin increase the risk for T1D also in a Caucasian population born and residing in a Mediterranean region (Continental Italy). This finding may be relevant for explaining different T1D incidence as prevalence of blue eyes differ substantially between northern and southern European Caucasians. Copyright. (C) 2011 John Wiley & Sons, Ltd
