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Vaginal immunology and microbiome composition: bacterial vaginosis in a macaque model
Get PDFNonhuman primates (NHPs) are important animal models for the study of human health and disease. In particular, the use of NHPs to study the vaginal microbiome and susceptibility to infections (such as HIV and herpesvirus) is exceptionally valuable due to the similarity in anatomy and physiology. An important aspect to this is maintaining a healthy vaginal microbiome which then minimizes colonization by pathogens and resulting inflammation along the mucosa. In women, conditions such as bacterial vaginosis (BV) are frequently treated with antibiotics such as metronidazole or clindamycin. Due to the excessive use of antimicrobials in medicine and agriculture, alternative compounds and therapies are highly desired to treat infections. Approaches that have been developed and used for vaginal infections includes the use of natural antimicrobials such as essential oils, probiotics, and live cultures, which mimic and function like antibiotics but lack development of resistance like classic antibiotics. However, these approaches have been minimally studied in humans and animals. Effectiveness of essential oils are anecdotal at best. Microbiome manipulation on the other hand has been investigated more thoroughly. Novel products are being distributed for medical use and are monotherapies containing Lactobacillus which colonize the vaginal mucosa (Ali et al., 2020; Brichacek et al., 2013; Lagenaur, Sanders-Beer, et al., 2011). Unfortunately, these therapies have limitations due to durability and individual response in women. By evaluating the extent by which the NHP vaginal mucosa can be colonized
with exogenously delivered bacteria, this animal model will highlight the NHP for use in translational studies which use essential oils and beneficial microbiome bacteria for vaginal delivery
Materiali fotoresponsivi innovativi e strutture supramolecolari
Get PDFThis thesis focuses on two main topics: photoresponsive azobenzene-based polymers and supramolecular systems generated by the self-assembly of lipophilic guanosines.
In the first chapters describe innovative photoresponsive devices and materials capable of performing multiple roles in the field of soft robotics and energy conversion. Chapter 2 describes a device obtained by coupling a photoresponsive liquid-crystalline network and a piezoelectric polymer to convert visible light into electricity. Chapter 3 deals with a material that can assume different shapes when triggered by three different stimuli in different environments. Chapter 4 reports a highly performing artificial muscle that contracts when irradiated.
The last two chapters report on supramolecular structures generated from functionalized guanosines dissolved in organic solvents. Chapter 6 illustrates the self-assembly into G-quadruplexes of 8- and 5’-functionalized guanosines in the absence of templating ions. Chapter 7 describes the supramolecular structure generated by the assembly of a lipophilic guanosine in the presence of silver cations.
Chapter 6 is reproduced from an already published paper, while the other chapters are going to be submitted to different journals in a couple of months.Questa tesi si concentra su due argomenti principali: polimeri fotoresponsivi a base di azobenzene e sistemi supramolecolari generati dall'autoassemblaggio di guanosine lipofile.
Nei primi capitoli vengono descritti dispositivi e materiali fotoresponsivi innovativi in grado di svolgere molteplici ruoli nel campo della robotica morbida e della conversione energetica. Il capitolo 2 descrive un dispositivo ottenuto dall'accoppiamento di una rete liquido-cristallina fotoresponsiva e di un polimero piezoelettrico per convertire la luce visibile in elettricità. Il capitolo 3 tratta di un materiale che può assumere forme diverse se innescato da tre diversi stimoli in ambienti diversi. Il capitolo 4 riporta un muscolo artificiale altamente performante che si contrae quando viene irradiato.
Gli ultimi due capitoli riportano strutture supramolecolari generate da guanosine funzionalizzate disciolte in solventi organici. Il capitolo 6 illustra l'autoassemblaggio in G-quadruplex di guanosine 8- e 5'-funzionalizzate in assenza di ioni templanti. Il capitolo 7 descrive la struttura supramolecolare generata dall'assemblaggio di una guanosina lipofila in presenza di cationi d'argento.
Il capitolo 6 è riprodotto da un lavoro già pubblicato, mentre gli altri capitoli saranno presentati a diverse riviste entro un paio di mesi
Clinical impact of next-generation sequencing multi-gene panel highlighting the landscape of germline alterations in ovarian cancer patients
Get PDFBRCA1 and BRCA2 are the most frequently mutated genes in ovarian cancer (OC), crucial both for the identification of cancer predisposition and therapeutic choices. However, germline variants in other genes could be involved in OC susceptibility. We characterized OC patients to detect mutations in genes other than BRCA1/2 that could be associated with a high risk to develop OC, and that could permit patients to enter the most appropriate treatment and surveillance program. Next-Generation Sequencing analysis with a 94-gene panel was performed on germline DNA of 219 OC patients. We identified 34 pathogenic/likely-pathogenic variants in BRCA1/2 and 38 in other 21 genes. Patients with pathogenic/likely-pathogenic variants in non-BRCA1/2 genes developed mainly OC alone compared to the other groups that developed also breast cancer or other tumors (p=0.001). Clinical correlation analysis showed that low-risk patients were significantly associated with platinum sensitivity (p<0.001). Regarding PARP inhibitors (PARPi) response, patients with pathogenic mutations in non-BRCA1/2 genes had significantly worse PFS and OS. Moreover, a statistically significant worse PFS was found for every increase of one thousand platelets before PARPi treatment. To conclude, knowledge about molecular alterations in genes beyond BRCA1/2 in OC could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies for OC patients
Sudden cardiac death in Emilia-Romagna: characteristics of the multidisciplinary network and results of the first four years
Get PDFIntroduzione: dal 2018 è attiva in Emilia-Romagna una rete multidisciplinare per i casi di morte cardiaca improvvisa (MCI). In questo studio sono riportate le caratteristiche della rete e i risultati dei primi quattro anni di attività.
Materiali e metodi: sono inclusi i casi di MCI avvenuti in Emilia-Romagna dal 2018 in soggetti con età > 1 anno e ≤55 anni. L’autopsia è stata eseguita secondo le raccomandazioni internazionali ed il cuore inviato all’Unità di Patologia Cardiovascolare del Policlinico di Sant’Orsola. A seconda degli scenari sono state eseguite analisi genetiche, tossicologiche e microbiologiche. In caso di patologie geneticamente determinate o nelle morti sine materia è stato avviato lo screening familiare.
Risultati: nei primi quattro anni di attività sono pervenuti 83 casi (età media 37 anni). In tutti i casi è stato eseguito un esame cardio-patologico completo e in 55 soggetti (66%) l’analisi genetica. Tra i 75 casi completati, è stata identificata una causa certa/altamente probabile di decesso in 66 (88%). Le patologie coronariche sono la patologia più frequentemente diagnostica (20 casi, 27%) seguita dalle cardiomiopatie (21%), mentre in 9 soggetti è stata riscontrata una malattia infiammatoria. L’indagine genetica è stata completata in 42 casi, identificando in 8 una mutazione causativa o una variante verosimilmente patogena (materiale inidoneo in 9). Successivamente, è stato eseguito lo screening in 14 famiglie di probandi deceduti per patologie non acquisite identificando sei soggetti di altrettante famiglie con un fenotipo positivo o dubbio. L’analisi genetica ha permesso di individuare quattro parenti con la stessa mutazione/variante verosimilmente patogena del probando. Complessivamente, in quattro soggetti è stato impiantato un defibrillatore per la prevenzione primaria della MCI.
Conclusioni: la rete multidisciplinare della MCI in Emilia-Romagna ha permesso di identificare una causa di decesso in quasi nove casi su dieci, diagnosticare diversi parenti affetti e approntare strategie preventive per la MCI.Background: a multidisciplinary network for sudden cardiac death (SCD) was established in 2018 in Emilia-Romagna with the purpose of identifying the causes of death and offer a familiar screening. In this study, the network’s characteristics and the results of the first four years are reported.
Methods: all cases of SCD aged > 1 year and ≤55 years occurred in Emilia-Romagna from 2018 were included. A full autoptic examination was performed according to international guidelines and the whole heart was sent to the Cardiovascular Pathology Unit of Bologna University Hospital. Depending on specific scenarios, genetic, toxicologic and microbiology tests were executed. Familiar screening was offered in all cases of potentially inherited diseases or in deaths sine materia.
Results: 83 SCD cases were collected (mean age 37 years). A full cardiac pathology examination was performed in all cases, followed by genetic tests in 55 (66%). Among the 75 completed cases, a certain/highly probable cause of death was identified in 66 (88%). Coronary diseases were diagnosed in 27% of cases, followed by 21% of cardiomyopathies, while inflammatory diseases were evident in 9 subjects. Genetic tests were completed in 42 cases (unsuitable material in 9), identifying a causative mutation or a likely pathogenic variant in 8 subjects. Subsequently, a familiar screening was performed in the 14 families of probands deceased for non-acquired diseases and in 6 subjects of different families, a positive or suspected phenotype for the proband’s condition was evident. Moreover, genetics identified a familiar causative mutation or likely pathogenic variant in 4 relatives. Overall, in four subjects an automatic defibrillator was implanted for SCD prevention.
Conclusions: the multidisciplinary design of Emilia-Romagna SCD network resulted in the identification of a certain/highly probable cause of death in nearly 90% of cases. Following familiar screening, several affected relatives were found and SCD prevention strategies adopted
Internet of healthcare (law): privacy and data protection aspects in an internet of everything
Get PDFThe purpose of this research study is to discuss privacy and data protection-related regulatory and compliance challenges posed by digital transformation in healthcare in the wake of the COVID-19 pandemic. The public health crisis accelerated the development of patient-centred remote/hybrid healthcare delivery models that make increased use of telehealth services and related digital solutions. The large-scale uptake of IoT-enabled medical devices and wellness applications, and the offering of healthcare services via healthcare platforms (online doctor marketplaces) have catalysed these developments. However, the use of new enabling technologies (IoT, AI) and the platformisation of healthcare pose complex challenges to the protection of patient’s privacy and personal data. This happens at a time when the EU is drawing up a new regulatory landscape for the use of data and digital technologies. Against this background, the study presents an interdisciplinary (normative and technology-oriented) critical assessment on how the new regulatory framework may affect privacy and data protection requirements regarding the deployment and use of Internet of Health Things (hardware) devices and interconnected software (AI systems). The study also assesses key privacy and data protection challenges that affect healthcare platforms (online doctor marketplaces) in their offering of video API-enabled teleconsultation services and their (anticipated) integration into the European Health Data Space. The overall conclusion of the study is that regulatory deficiencies may create integrity risks for the protection of privacy and personal data in telehealth due to uncertainties about the proper interplay, legal effects and effectiveness of (existing and proposed) EU legislation. The proliferation of normative measures may increase compliance costs, hinder innovation and ultimately, deprive European patients from state-of-the-art digital health technologies, which is paradoxically, the opposite of what the EU plans to achieve
Adapting fruit production to climate change: how to increase intrinsic fruit quality and save water through deficit irrigation scheduling.
Get PDFFruit crops are an important resource for food security, since more than being nutrient they are also a source of natural antioxidant compounds, such as polyphenols and vitamins. However, fruit crops are also among the cultivations threatened by the harmful effects of climate change This study had the objective of investigating the physiological effects of deficit irrigation on apple (2020-2021), sour cherry (2020-2021-2022) and apricot (2021-2022) trees, with a special focus on fruit nutraceutical quality. On each trial, the main physiological parameters were monitored along the growing season: i) stem and leaf water potentials; ii) leaf gas exchanges; iii) fruit and shoot growth. At harvest, fruit quality was evaluated especially in terms of fruit size, flesh firmness and soluble solids content. Moreover, it was performed: i) total phenolic content determination; ii) anthocyanidin concentration evaluation; and iii) untargeted metabolomic study.
Irrigation scheduling in apricot, apple and sour cherry is surely overestimated by the decision support system available in Emilia-Romagna region. The water stress imposed on different fruit crops, each during two years of study, showed as a general conclusion that the decrease in the irrigation water did not show a straightforward decrease in plant physiological performance. This can be due to the miscalculation of the real water needs of the considered fruit crops. For this reason, there is the need to improve this important tool for an appropriate water irrigation management. Furthermore, there is also the need to study the behaviour of fruit crops under more severe deficit irrigations. In fact, it is likely that the application of lower water amounts will enhance the synthesis of specialized metabolites, with positive repercussion on human health. These hypotheses must be verified
One archive, many readings. Personal archives as complex networks in the semantic web
Get PDFPersonal archives are the archives created by individuals for their own purposes. Among these are the library and documentary collections of writers and scholars. It is only recently that archival literature has begun to focus on this category of archives, emphasising how their heterogeneous nature necessitates the conciliation of different approaches to archival description, and calling for a broader understanding of the principle of provenance, recognising that multiple creators, including subsequent researchers, can contribute to shaping personal archives over time by adding new layers of contexts.
Despite these advances in the theoretical debate, current architectures for archival representation remain behind. Finding aids privilege a single point of view and do not allow subsequent users to embed their own, potentially conflicting, readings. Using semantic web technologies this study aims to define a conceptual model for writers' archives based on existing and widely adopted models in the cultural heritage and humanities domains. The model developed can be used to represent different types of documents at various levels of analysis, as well as record content and components. It also enables the representation of complex relationships and the incorporation of additional layers of interpretation into the finding aid, transforming it from a static search tool into a dynamic research platform.
The personal archive and library of Giuseppe Raimondi serves as a case study for the creation of an archival knowledge base using the proposed conceptual model. By querying the knowledge graph through SPARQL, the effectiveness of the model is evaluated. The results demonstrate that the model addresses the primary representation challenges identified in archival literature, from both a technological and methodological standpoint. The ultimate goal is to bring the output par excellence of archival science, i.e. the finding aid, more in line with the latest developments in archival thinking
Sex differences in cardiovascular features and outcomes of patients with cancer hospitalized for COVID-19
Get PDFObiettivo: Lo scopo principale di questo studio è analizzare lo sviluppo di complicanze cardiovascolari (CV) nei pazienti con neoplasia e malattia moderata-severa da COVID-19 e valutare differenze di genere per il rischio di mortalità intraospedaliera o di complicanze CV.
Materiali e Metodi. Popolazione oggetto di studio. Pazienti inclusi nel registro ISACS-COVID 19 (ClinicalTrials.gov: NCT05188612), dati raccolti a partire da Febbraio 2020 a Luglio 2022. I pazienti arruolati sono stati reclutati da centri ospedalieri di cinque paesi: Italia, Croazia, Macedonia, Serbia e Romania. Le caratteristiche d’inclusione comprendono: età >18 anni, essere ospedalizzati e avere diagnosi certa d’infezione da SARS-CoV2. Gli endpoint analizzati sono stati: mortalità intraospedaliera e lo sviluppo di scompenso cardiaco acuto (SCA) nei pazienti con neoplasia.
Risultati. La popolazione finale oggetto dello studio era di 4,014 pazienti ospedalizzati per malattia da COVID-19. Di questi circa l’8% risultava affetto da neoplasia. I pazienti con neoplasia risultavano essere più frequentemente donne (49% vs 40%, p=0.004), con un’età media più alta (68.3±12.95 vs 65.2±15.6, p<0.001) ma con profilo di rischio CV simile ai pazienti liberi da neoplasia. A seguito di analisi logistica di regressione multivariata, le donne non risultavano avere un incremento del rischio di mortalità intraospedaliera (OR 0.83;95%CI 0.66-2.45), mentre la presenza di tumore era significativamente associata ad incremento di mortalità (OR 1.68;95%CI 1.16-2.45). Restringendo le analisi di regressione logistica ai pazienti oncologici, le donne presentavano un incremento del rischio di sviluppo di SC acuto (OR3.07;95%CI 1.14 – 8.30) così come lo era la presenza di tumore al seno (OR 2.26; 95%CI 1.38 – 12.1).
Conclusioni. La presenza di neoplasia rappresenta una condizione che incrementa il rischio di mortalità intraospedaliera nei pazienti ricoverati con COVID-19, mentre il genere femminile no. Le donne sembrano avere un rischio aumentato di sviluppo di SC acuto soprattutto se presentano un tumore al senoObjective: The main purpose of this study is to analyze the development of cardiovascular (CV) complications in patients with cancer and moderate to severe COVID-19 disease and to evaluate gender differences for the risk of in-hospital mortality or CV complications.
Materials and methods. Study population. Patients included in the ISACS-COVID 19 registry (ClinicalTrials.gov: NCT05188612), whose data were collected from February 2020 to July 2022. Enrolled patients were recruited from various hospital centers in five countries: Italy, Croatia, Macedonia, Serbia and Romania. The inclusion characteristics include: age greater than 18 years, being hospitalized and having a certain diagnosis of SARS-CoV2 infection. The endpoints analyzed were in-hospital mortality and the development of acute heart failure (ACS) in patients with cancer.
Results. The final study population was 4,014 patients hospitalized for COVID-19 disease. Of these, approximately 8% had active cancer. Patients with cancer were more frequently women (49% vs 40%, p=0.004), with a higher mean age (68.3±12.95 vs 65.2±15.6, p<0.001) but had a CV risk profile similar to cancer-free patients. Following multivariate logistic regression analysis, female gender was not associated with an increase in the risk of in-hospital mortality (OR 0.83; 95%CI 0.66-2.45), while the presence of cancer was significantly associated with an increase in mortality (OR 1.68 ; 95% CI 1.16-2.45). Restricting logistic regression analyzes to cancer patients, women had an increased risk of developing acute HF (OR 3.07; 95%CI 1.14 – 8.30) as well as the presence of breast cancer (OR 2.26; 95% CI 1.38 – 12.1).
Conclusions. The presence of neoplasia represents a condition that increases the risk of in-hospital mortality in patients hospitalized with COVID-19, while the female gender does not. Women, on the other hand, seem to have an increased risk of developing acute HF especially if they have breast cance
Influencable autonomy and predictable freedom in the IoE
Get PDFThis thesis investigates how individuals can develop, exercise, and maintain autonomy and freedom in the presence of information technology. It is particularly interested in how information technology can impose autonomy constraints.
The first part identifies a problem with current autonomy discourse: There is no agreed upon object of reference when bemoaning loss of or risk to an individual’s autonomy. Here, thesis introduces a pragmatic conceptual framework to classify autonomy constraints. In essence, the proposed framework divides autonomy in three categories: intrinsic autonomy, relational autonomy and informational autonomy.
The second part of the thesis investigates the role of information technology in enabling and facilitating autonomy constraints. The analysis identifies eleven characteristics of information technology, as it is embedded in society, so-called vectors of influence, that constitute risk to an individual’s autonomy in a substantial way. These vectors are assigned to three sets that correspond to the general sphere of the information transfer process to which they can be attributed to, namely domain-specific vectors, agent-specific vectors and information recipient-specific vectors.
The third part of the thesis investigates selected ethical and legal implications of autonomy constraints imposed by information technology. It shows the utility of the theoretical frameworks introduced earlier in the thesis when conducting an ethical analysis of autonomy-constraining technology. It also traces the concept of autonomy in the European Data Lawsand investigates the impact of cultural embeddings of individuals on efforts to safeguard autonomy, showing intercultural flashpoints of autonomy differences.
In view of this, the thesis approaches the exercise and constraint of autonomy in presence of information technology systems holistically. It contributes to establish a common understanding of (intuitive) terminology and concepts, connects this to current phenomena arising out of ever-increasing interconnectivity and computational power and helps operationalize the protection of autonomy through application of the proposed frameworks
Multiscale modeling of light-harvesting systems based on rhodamine B aggregates
Get PDFRhodamine B (RB) has been successfully exploited in the synthesis of light harvesting systems, but since RB is prone to form dimers acting as quenchers for the fluorescence, high energy transfer efficiencies can be reached only when using bulky and hydrophobic counterions acting as spacers between RBs. In this PhD thesis, a multiscale theoretical study aimed at providing insights into the structural, photophysical and optical properties of RB and its aggregates is presented. At the macroscopic level (no atomistic details) a phenomenological model describing the fluorescence decay of RB networks in presence of both quenching from dimers and exciton-exciton annihiliation is presented and analysed, showing that the quenching from dimers affects the decay only at long times, a feature that can be exploited in global fitting analysis to determine relevant chemical and photophysical information. At the mesoscopic level (atomistic details but no electronic structure) the RB aggregation in water in presence of different counterions is studied with molecular dynamics (MD) simulations. A new force field has been parametrized for describing the RB flexibility and the RB-RB interaction driving the dimerization. Simulations correctly predict the RB/counterion aggregation only in presence of bulky and hydrophobic counterion and its ability to prevent the dimerization. Finally, at the microscopic level, DFT calculations are performed to demonstrate the spacing action of bulky counterions, but standard TDDFT calculations are showed to fail in correctly describing the excited states of RB and its dimers. Moreover, also standard procedures proposed in literature for obtaining ad hoc functionals are showed to not work properly. A detailed analysis on the effect of the exact exchange shows that its short-range contribution is the crucial quantity for ameliorating results, and a new functional containing a proper amount of such an exchange is proposed and successfully tested