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Investigating the Timing and Predictive Value of Clinical Conditions Preceding Multiple Sclerosis in the UK Biobank’s Population-Based Cohort
No full textIntroduction: Multiple Sclerosis (MS) is a complex autoimmune disease[1]. Growing evidence suggests a prodromal phase marked by increased healthcare use and various clinical symptoms before diagnosis, such as pain, fatigue, urinary issues, and mental health conditions[2]. These objectives are particularly relevant due to the recently highlighted increase in the age at MS onset due to a higher incidence in late-onset MS (LOMS) cases, which may result from the accumulation of different conditions[3]. However, prior studies often relied on limited time windows (5 years prior the diagnosis), introducing temporal bias by over-emphasizing conditions occurring closer to MS diagnosis, other than failing to discover associated early conditions occurring many years prior the diagnosis[4]. Moreover, the predictive value of MS prodromes and their temporal trajectories have not been explored yet.
Objectives: To investigate these aspects, we used the large UK Biobank’s population-based cohort, which provided the clinical history for each individual through ICD-10 diagnosis codes and diagnoses dates. Specifically, using time-to-event analyses, we aimed to (i) identify early conditions associated with later MS diagnosis, (ii) assess their predictive value, and (iii) map disease trajectories leading to MS.
Methods: We assessed associations between 600 clinical conditions and MS risk in 477,421 individuals using Cox models adjusted for demographics, smoking, and MS polygenic risk score (MS-PRS). To account for multiple testing, we applied a False Discovery Rate (FDR) correction at 0.05. Statistically significant conditions were classified based on their timing of appearance in relation to MS diagnosis, i.e., >5 years, 3-5 years, 1-3 years, or within 1 year, as well as based on their clinical relationship with MS, i.e., onset symptoms, prodromal conditions, risk/protective factors, or unknown relationship. We then included these significant conditions in a LASSO Cox regression (5-fold cross-validation on 70% training-validation set) to identify key predictors, with performance assessed by the C-index and age-dependent Area Under the Curve (AUC) in the 30% test set[5]. To rank the most important conditions based on their predictive value, we used permutations. Lastly, temporal trajectories of MS-associated conditions were analyzed in MS cases using conditional logistic regression models[6].
Results: We identified 192 conditions associated with MS, of which only ~20% were onset symptoms. Integrating these conditions into a predictive model already including demographics and smoking improved the C-index from 0.65 to 0.71. Among the thirty model-selected best predictors, ~25% were prodromal conditions, including neuromuscular diseases, thromboembolism, and depression which typically occurred more than five years before MS diagnosis. Including MS-PRS further increased the C-index to 0.78, with an age-dependent AUC exceeding 0.80 in individuals over 50 years. Trajectory analysis highlighted migraine as a common early diagnosis, often followed by hypertension, depression, and dorsalgia.
Conclusions: Our findings highlight early conditions and diagnostic trajectories of MS, supporting the existence of a prodromal phase. Specifically, while genetic risk represented the strongest predictor in adulthood, clinical history represented the strongest predictor in individuals over 50 years of age[7]. Importantly, the identified disease trajectories showed that MS onset symptoms occurring closer to diagnosis were themselves predictable by earlier prodromal conditions. These insights could improve MS prediction and facilitate earlier detection, particularly for late-onset cases. Future research should validate these results in independent cohorts, and explore how integrating subtle signs and symptoms, lifestyle factors and biomarkers could further refine and enhance the accuracy for an MS prediction tool to be implemented and tested in the clinical practice
Blood donation in young people: estimation of education and awareness in Rome high school students using translated questionnaires
No full textAbstract
Background: Ensuring a stable blood supply is a critical public health challenge, with young adults representing a vital pool of potential donors. Education and awareness are key to fostering positive attitudes and behaviors toward blood donation among youth.
Objectives: This study aimed to assess the impact of educational interventions on the willingness of high school students in Rome to donate blood and to validate the Italian translation of two established questionnaires measuring knowledge and motivation related to blood donation.
Materials and methods: An observational, prospective, cross-sectional study was conducted among senior students at the “Democrito” high school in Rome during the 2022–23 academic year. Eligible students (aged 18 or older) completed two validated and translated questionnaires before and after a series of educational lectures on blood donation. The reliability and content validity of the translated instruments were evaluated, and changes in students’ intentions and attitudes were analyzed using the McNemar test.
Results: Of 54 students with matched pre- and post-intervention responses, the proportion expressing a positive attitude toward blood donation increased from 57.4% to 75.9% following the educational sessions (p = 0.0213), indicating a statistically significant improvement. Motivations for donation included altruism, health benefits, social approval, and practical incentives. Despite increased willingness, only a small fraction of students who expressed intent ultimately donated blood, highlighting a gap between intention and action. The translated questionnaires demonstrated high content validity (CVI: 0.975 and 0.908) and were well-understood by the target population.
Conclusions: Educational interventions significantly enhanced students’ willingness to donate blood, underscoring the importance of targeted awareness campaigns in schools. However, bridging the gap between intention and actual donation remains a challenge, necessitating further strategies to address logistical and psychological barriers. The validated Italian questionnaires provide reliable tools for future research and program evaluation in this context.
 
Do COVID-19 Pandemic Increase the Risk of Non-COVID-19 Mortality in Frail Elderly? A Real-World Retrospective Cohort Study
No full textIntroduction
During the SARS-Cov2 pandemic, urgent measures were carried out to face the increasing healthcare demand due to the pandemic, including, among others, the suspension of non-urgent hospital activities and specialist consultations unrelated to COVID-19 disease [1]. These measures, however, significantly restricted access to hospital facilities for patients with chronic conditions, including cancer patients and frail elderly, suggesting a potential increased risk of non-COVID-19 mortality due to a lack of care of these vulnerable populations.
Aims
The aim of the study was to compare the risk of non-COVID-19 mortality during the pandemic period with the pre-pandemic period specifically among elderly individuals with at least one chronic disease (vulnerable subjects) exploiting the data available in the healthcare utilization data from the Local Health Authority (LHA) of Vercelli province, Piedmont, Italy.
Methods
This cohort study was conducted using the data available in the healthcare utilization databases of the LHA of Vercelli including: i) the registry of healthcare beneficiaries assisted by the LHA of Vercelli ii) the drug prescription database, iii) the hospital discharge database, iv) the exemptions databases and v) the mortality registry. The information included in the different databases belonging to the same subject were linked through an anonymized individual identification code which prevented the identification of the people included in the databases.
Two cohorts of subjects were selected: the pre-pandemic cohort included all subjects assisted by the LHA of Vercelli alive the 1st January 2018, aged 65 years or older and affected by at least one chronic condition in 2017. The pandemic cohort was made of all subjects alive the 1st January 2020, aged 65 years or older and affected by at least one chronic condition in 2019
The outcome of interest was death due to causes other than COVID-19. The subjects of both cohorts identified in the mortality registry with a cause of death different from COVID-19 were considered as events.
The information regarding age, sex, vulnerability and the chronic disease from which cohorts’ members were affected were retrieved for all subjects. The vulnerability level was defined according to the severity index, an index assigning to each chronic condition the corresponding severity score (from 1 not severe condition to 3 severe condition) according to the Italian Ministry of Health chronic diseases classification available in the COVID-19 vaccination plan [2]. Subjects were classified according to the most severe disease as non-vulnerable (severity index 0-1), vulnerable (severity index 2) and extremely vulnerable (severity index 3), further detail on the severity index are reported elsewhere [3].
Descriptive statistics were used to summarize the demographic and clinical information collected on study subjects overall and according to cohort. Categorical variables were reported as absolute frequencies and percentages by cohort and overall. The Chi square test was used to compare the distribution of subjects’ characteristics between cohorts. Multivariable Fine and Gray [4] model was used to calculate the adjusted sub-distribution hazard ratios (asHR) and the corresponding 95%CI to evaluate the relationship between time periods and non-COVID-19 mortality accounting for COVID-19 mortality as competing risk. The rule-out approach was used to assess the impact of the unmeasured confounder seasonal flu on the association estimate.
Results
91777 elderly subjects with at least one chronic disease were included in the study, 46048 belong to the cohort 2018 and 45729 to the cohort 2020. Overall, the proportion of females were slightly more frequent than males (57.58% vs 42.42%) and the mean age was 76.64 years. 44.63% of subjects were classified as vulnerable. Overall, the proportion of deaths tends to increase from 2018 to 2021 varying from 4.62% in 2018 to 5.40% in 2021, however, considering only non-COVID-19 mortality, the proportions of death in 2020 and 2021 were lower than 2019 (4.06% and 4.85% respectively).
Table 1 reports asHR and the corresponding 95%CI derived from multivariable Fine and Gray models for the association between time periods and non-COVID-19 mortality and the p-value of the trend test for age and vulnerability classes.
Table 1 Adjusted subdistribution hazard ratios (asHR), the corresponding 95% confidence intervals (95%CI), for the association between time periods and non-COVID-19 mortality and the p-value of the trend test.
The results of Fine and Gray model show that, among subjects that did not die due to COVID-19, the risk of non-COVID-19 mortality was 10% lower during the pandemic period compared to the pre-pandemic one. The results of the rule-out analysis show that part of the decreased risk of non-COVID-19 mortality observed in the pandemic period could be explained by decreased mortality for flu.
Conclusions
A decreased risk of non-COVID-19 mortality was observed during the pandemic period compared to the pre-pandemic one. An explanation may be that during the pandemic, many frail individuals died from COVID-19, resulting in a chronically ill elderly population that was, on average, healthier and had a lower mortality rate than in the pre-pandemic period, also due to the absence of flu-related deaths. Lack of care did not seem to affect non-COVID-19 mortality during the pandemic period in frail elderly
The Association between Individual and Area-Level Socioeconomic Indicators with Mortality and Health Outcomes in a Female Cohort Living in The Metropolitan Area of Naples (PROGETTO ATENA)
No full textIntroduction
Unfavorable socioeconomic conditions are associated with an increased risk of death and the onset of various diseases in the general population across all countries worldwide [1]. The Metropolitan Area of Naples (ANM), characterized by high deprivation, social polarization, and mortality, represents an urban context with high social heterogeneity, offering the opportunity to analyze health inequalities in relation to socioeconomic position (SEP). The relationship between socioeconomic position and health, analyzed through individual and geographical indicators, is crucial to guide effective prevention strategies.
Objectives
We present here a study whose objectives were (1) to assess the association between socioeconomic position and lifestyle-related risk factors and (2) to estimate the extent to which socioeconomic inequalities, measured at both individual and area levels, influence mortality, breast cancer incidence and cardiovascular diseases in a female cohort from the Progetto ATENA.
Methods
The Progetto ATENA is a prospective cohort study whose main goal was to investigate the causes of certain chronic diseases that affect the female population more significantly at different life stages. Between 1993 and 1996, the project enrolled 5.062 women aged between 30 and 70 years, residing in the ANM. To estimate incidence and mortality rates, two follow-ups on the participants\u27 health status were conducted (in 2010 and 2016) [2].
Socioeconomic position was measured both at the individual and area levels. At the individual level, the Relative Index of Inequality (RII) was used, divided into tertiles representing decreasing levels of education. At the area level, the 2001 Italian Deprivation Index (DI) [3] was used, calculated by census block, georeferenced according to the residential address, and classified into population quintiles.
Associations with the endpoints (overall mortality, breast cancer, cardiovascular events and coronary heart disease) were studied using Cox proportional hazards regression models [4] adjusted for age, treated as the underlying time variable. For each endpoint, four multivariate models were built: Model 1 included RII tertiles and DI quintiles as covariates; Model 2 included Model 1 covariates plus clinical risk factors (systolic blood pressure, total cholesterol, and diabetes); Model 3 included Model 1 covariates plus lifestyle-related risk factors (smoking, physical activity, BMI, waist circumference, alcohol consumption, Mediterranean diet score, and energy intake); Model 4 included the covariates from both previous models. For breast cancer incidence, Model 2 and Model 4 were developed considering clinical variables such as age at menarche and number of children (instead of total cholesterol and systolic blood pressure). Participants with missing values for the mentioned variables were excluded from the analysis. Trend analyses were also performed.
Results
Among the 4.814 women included, follow-up recorded 411 deaths, 225 breast cancer diagnoses, 241 cardiovascular events (CVD), and 150 coronary heart disease events (CHD). At baseline, a positive association between the two SEP indices was observed (r=0.318). Both DI and RII were positively associated with systolic blood pressure, BMI, waist circumference, and waist-to-height ratio. Total and HDL cholesterol were negatively associated with both SEP indices. Age and energy intake were positively associated with RII and negatively with DI.
In the mortality analysis, a significant association with DI was observed, with hazard ratios (HR) of 1.56 (Q5 vs Q1, 95%CI 1.13–2.13, p=0.006) in Model 1 and 1.45 (Q5 vs Q1, 95%CI 1.05–2.02, p=0.026) in Model 4; significant trends (p=0.014, p=0.046). Similar results were found for both Model 2 and Model 3.
Similarly, an association between breast cancer incidence and DI was observed in Model 1 (Q5 vs Q1, HR 1.57, 95%CI 1.04–2.38, p=0.032); a significant trend was also observed (p=0.042). Model 2 showed comparable outcomes. In none of the models was RII associated with mortality or breast cancer.
Survival analysis revealed, in all models, a significant association between RII and CVD, with HRs of 1.62 (Q5 vs Q1, 95%CI 1.18–2.21, p=0.003) and 1.44 (Q5 vs Q1, 95%CI 1.03–2.01, p=0.034) in Model 1 and Model 4, respectively. The trends were also significant (p=0.003, p=0.043). Comparable results were observed in Model 2 and Model 3.
Likewise, an association between CHD and RII was observed in all models with HRs of 1.94 (Q5 vs Q1, 95%CI 1.31–2.87, p=0.001) and 1.62 (Q5 vs Q1, 95%CI 1.07–2.48, p=0.024) and significant trends (p=0.001, p=0.025). Analysis revealed similar outcomes for Model 2 and Model 3. In contrast, no significant association between CVD and CHD with DI was found in any of the models.
Conclusions
The analysis highlights that the local socioeconomic environment influences mortality and breast cancer more than individual education. Conversely, individual education seems to have a greater impact on the risk of cardiovascular events and coronary heart disease than area-level deprivation. In the comparison between Q5 and Q1, an increase of up to 56% in mortality risk and up to 62% in breast cancer risk was observed; in the comparison between RII 3 and RII 1, an increase of up to 62% in CVD risk and up to 94% in CHD risk was observed
Gemma Sena Chiesa in Angera. The archaeological excavations of the universities of Milano and Pavia
No full textIl contributo è dedicato a Gemma Sena Chiesa e alle sue ricerche sul vicus romano di Angera, in particolare agli scavi condotti nella necropoli e nell’abitato dalle università di Milano e di Pavia fra il 1975 e il 1986, da lei diretti, e agli studi che ne sono derivati.The contribution is dedicated to Gemma Sena Chiesa and her research on Roman vicus of Angera, in particular to the archaeological excavations conducted in the necropolis and in the town by the universities of Milano and Pavia between 1975 and 1986, directed by her, and to the resulting studies
Dialectics and Reason as Self-Criticism of the Real. The Interpretation of the Middle Ages in Hegel\u27s Lectures on the Philosophy of History and in the Lectures on the History of Philosophy
No full textThe article examines how Hegel analyzes the Middle Ages as an historical and cultural entity. According to Hegel, history also means history of philosophy, just as philosophy is fully part of the material historical process. In both dimensions, Hegel seeks the evolution of the Spirit and the development of what he considers the telos of history: the human subject’s awareness that consciousness is constituted by freedom. Historical periods and processes of intellectual development are conceived by Hegel as unitary entities that evolve cumulatively, even if their unfolding is not linear. Hegel’s thought can be defined as structurally critical, because it treats the relationship between subject and world as always to be transcended, and reality can never be hypostatized or considered only in itself, but it must always be correlated with its own negative, with what it is not yet, in view of the full development of human faculties and the possibilities of Reason. The central question of the article is thus: how does Hegel conceptualize the Middle Ages within this theoretical structure? What place does he assign it in the history of Spirit’s evolution?L’articolo esamina il modo in cui Hegel analizza il medioevo come entità storica e culturale. Per Hegel, la storia è anche storia della filosofia, così come la filosofia è pienamente parte del processo storico materiale. In entrambe le dimensioni, Hegel va alla ricerca dell’evoluzione dello Spirito e dello sviluppo di quello che considera il telos della Storia: la consapevolezza della coscienza umana di essere destinata alla libertà. Tanto i periodi storici che i processi di sviluppo del pensiero sono pensati da Hegel come entità unitarie, che si evolvono cumulativamente, anche se il loro dispiegamento non è lineare. Il pensiero di Hegel, da questo punto di vista, è strutturalmente critico, perché considera il rapporto tra soggetto e mondo e le forme della vita associata (lo spirito oggettivo) come sempre insufficienti, nel quadro di una realtà – quella storica come quella della coscienza – che non può mai essere ipostatizzata, ma va sempre correlata al proprio negativo, a ciò che non è ancora, in vista del pieno sviluppo della facoltà umane e delle possibilità della Ragione. La domanda al centro dell’articolo è dunque la seguente: come pensa Hegel il Medioevo all’interno di questa struttura teorica? Che posto gli assegna nell’evoluzione dello spirito?
The article examines how Hegel analyzes the Middle Ages as an historical and cultural entity. According to Hegel, history also means history of philosophy, just as philosophy is fully part of the material historical process. In both dimensions, Hegel seeks the evolution of the Spirit and the development of what he considers the telos of history: the human subject’s awareness that consciousness is constituted by freedom. Historical periods and processes of intellectual development are conceived by Hegel as unitary entities that evolve cumulatively, even if their unfolding is not linear. Hegel’s thought can be defined as structurally critical, because it treats the relationship between subject and world as always to be transcended, and reality can never be hypostatized or considered only in itself, but it must always be correlated with its own negative, with what it is not yet, in view of the full development of human faculties and the possibilities of Reason. The central question of the article is thus: how does Hegel conceptualize the Middle Ages within this theoretical structure? What place does he assign it in the history of Spirit’s evolution
Dalla rete alla pagina e ritorno: il fenomeno socio-letterario del romance italiano attraverso due casi di studio (Erin Doom e Rokia)
No full textThe article describes the characteristics and investigates the mechanisms behind the recent socio-literary intermedial phenomenon of romance, and it finally examines two case studies from the Italian landscape: Erin Doom and Rokia. The analysis focuses on their debut works, Fabbricante di lacrime (Magazzini Salani 2021) and The Truth Untold. La verità nascosta (Magazzini Salani 2022), and is conducted by relating the textual level with the contextual one, considering the entire production chain: from digital writing and promotion of texts on the social reading platform Wattpad to the composition and publication of books through the filters of traditional publishing.L’articolo indaga le caratteristiche e i meccanismi di funzionamento del recente fenomeno socio-letterario intermediale del romance, affrontando due casi di studio del panorama italiano: Erin Doom e Rokia. L’analisi si concentra sulle loro opere prime, Fabbricante di lacrime (Magazzini Salani 2021) e The Truth Untold. La verità nascosta (Magazzini Salani 2022), e fa reagire il piano testuale con quello contestuale, tenendo conto dell’intera filiera produttiva: dalle fasi di stesura e promozione dei testi sulla piattaforma digitale di social reading Wattpad, a quelle di composizione ed edizione dei libri attraverso le maglie dell’editoria tradizionale
Mariacristina Cavecchi, The Art Gallery on Stage. New Vistas on Contemporary British Playwriting
No full textMariacristina Cavecchi, The Art Gallery on Stage. New Vistas on Contemporary British Playwriting
(London-New York, Bloomsbury Methuen Drama Engage, 2024, 290 pp. ISBN 9781350330702)Mariacristina Cavecchi, The Art Gallery on Stage. New Vistas on Contemporary British Playwriting
(London-New York, Bloomsbury Methuen Drama Engage, 2024, 290 pp. ISBN 9781350330702
LA MEDIAZIONE E L’EDUCAZIONE LINGUISTICA: DOCENTI E APPRENDENTI COME MEDIATORI IN CLASSE: Monografia. Contributi di Marisa Cavalli, Cecilia Bartoli, Cristiana Cervini, Giulia Ciaramita, Clelia Maria Farina, Francesca Ferrucci, Ivana Fratter, Luca Lòtano, Emanuela Paone, Giulia Peri, Giulia Pizzolato, Cecilia Varcasia
No full textContributi di Marisa Cavalli, Cecilia Bartoli, Cristiana Cervini, Giulia Ciaramita, Clelia Maria Farina, Francesca Ferrucci, Ivana Fratter, Luca Lòtano, Emanuela Paone, Giulia Peri, Giulia Pizzolato, Cecilia Varcasi
PERCEZIONE E RAPPRESENTAZIONE DELL’ITALIANITÀ IN AFRICA. IL CASO DELLA CUCINA ITALIANA IN SUDAFRICA
No full textIl contributo analizza la rappresentazione e la percezione dell’italianità in Sudafrica attraverso la cucina, considerata una delle principali espressioni del made in Italy. L’indagine combina un’analisi linguistico-semiotica di due spot pubblicitari dell’azienda Fatti’s & Moni’s con un questionario sociolinguistico somministrato a italiani residenti in Sudafrica. Gli spot, veri e propri dispositivi semiotici, costruiscono un immaginario di italianità ibrido e glocale, fondato sulla convivialità, la famiglia e il gusto. I dati dei questionari confermano la centralità simbolica della cucina italiana nella definizione identitaria dei connazionali all’estero. L’articolo propone una lettura del rapporto tra pubblicità, pratiche alimentari e linguistic landscape/soundscape mostrando come la lingua e i simboli italiani contribuiscano alla costruzione di un paesaggio linguistico-culturale transnazionale.
Perception and Representation of Italian Identity in Africa: The Case of Italian Cuisine in South Africa
This paper explores how Italian identity is represented and perceived in South Africa through the lens of cuisine, one of the key expressions of Made in Italy. The study combines a linguistic-semiotic analysis of two Fatti’s & Moni’scommercials with data from a sociolinguistic questionnaire administered to Italians living in South Africa. The commercials function as semiotic devices that construct a hybrid, glocal imagery of Italianness centered on conviviality, family, and taste. The questionnaire results confirm the symbolic role of Italian cuisine in shaping diasporic identities. The article situates these findings within the framework of the linguistic landscape and soundscape, highlighting how Italian language and cultural symbols contribute to a transnational linguistic and cultural space.Perception and Representation of Italian Identity in Africa: The Case of Italian Cuisine in South Africa
This paper explores how Italian identity is represented and perceived in South Africa through the lens of cuisine, one of the key expressions of Made in Italy. The study combines a linguistic-semiotic analysis of two Fatti’s & Moni’scommercials with data from a sociolinguistic questionnaire administered to Italians living in South Africa. The commercials function as semiotic devices that construct a hybrid, glocal imagery of Italianness centered on conviviality, family, and taste. The questionnaire results confirm the symbolic role of Italian cuisine in shaping diasporic identities. The article situates these findings within the framework of the linguistic landscape and soundscape, highlighting how Italian language and cultural symbols contribute to a transnational linguistic and cultural space