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Liberi dall’obbligo e dalla sanzione : Il pensiero di Jean-Marie Guyau in una prospettiva giusfilosofica: tra anomia e generatività
No full textIn un tempo attraversato dalla crisi delle certezze, questo volume ritorna al pensiero
del filosofo francese Jean-Marie Guyau (1854-1888), al quale si deve la prima
tematizzazione del concetto di anomia come liberazione della morale dalle costrizioni
dell’obbligo e della sanzione.
Attraverso una lettura giusfilosofica il testo la esplora come spazio generativo,
capace di far scaturire nuove forme di responsabilità e di relazione.
Seguendo questa via, le questioni di coscienza, intese come condizioni in cui le esistenze di animali umani e non umani divengono rilevanti dal punto di vista etico e
giuridico, così come quelle legate all’intelligenza artificiale e alle nuove tecnologie,
segnano una soglia critica in cui riconfigurare la dignità e la solidarietà.
La prospettiva di Guyau, che si concretizza nelle possibilità morali che si aprono
immaginando umani liberi dall’obbligo e dalla sanzione, suggerisce di (ri)pensare la
libertà non come assenza di norme o di legami, ma come capacità creativa di inventarne di nuovi.
L’eredità filosofica del filosofo consiste proprio in questa scommessa: che la vita,
lasciata libera dall’obbligo e dalla sanzione, sappia (ancora) generare valori, senso
e solidarietà, seppure in modi inattesi, in un avvenire che, per quanto irreligioso è,
ancora, incerto ma possibile
Exploring regional inequities in food safety practices and food security in Italy: A cross-sectional study
No full textObjective This study examined regional disparities in food security and food safety knowledge and behavior among Italian adults. Methods Between January and June 2024, we conducted a cross-sectional anonymous online survey targeting Italian residents aged ≥18. The sample size was calculated a priori assuming a 50% prevalence, 95% confidence, and 3% margin of error, yielding a target of 1067 participants. Validated Italian versions of the Food Security Survey Module (It-FSSM) and the Food Safety Knowledge and Behavior Questionnaire (It-FSKB) were employed to assess participants’ knowledge and behaviors. Sociodemographic data, including age, sex, body mass index (BMI), educational level, physical activity, smoking habits, and food apps usage, were collected. Multinomial logistic regression—adjusted for age, sex, BMI, and educational level—was used to evaluate regional differences. Results Among 1752 participants (70.4% women; mean age: 36.01 ± 13.84 y), those in the South area and Islands were significantly less likely to report high food safety knowledge (relative risk ratio [RRR] = 0.66; 95% confidence interval [CI]: 0.54–0.82; P = 0.000) and high food safety behaviors (RRR = 0.64; 95% CI: 0.52–0.79; P < 0.001), and more likely to experience moderate food insecurity (RRR = 1.64; 95% CI: 1.00–2.69; P = 0.048) compared to participants to the North. Participants in the Center were over twice likely than those in the North to report high food security versus very low (RRR = 2.72; 95% CI: 1.15–6.43; P = 0.023) and were also 30% less likely to use food delivery apps rarely rather than not at all (RRR = 0.70; 95% CI: 0.50–0.97; P = 0.034). Conclusions This study highlights significant regional disparities, with the South area and Islands facing the greatest challenges. These findings provide evidence to guide targeted public health interventions and policies promoting food safety and security across Italy
'ORGANIZATIONAL HEALTH LITERACY' COME MODELLO PER RIPENSARE L'OSPEDALE IN UN'OTTICA INCENTRATA SUL PAZIENTE
No full textINTRODUZIONE
Nel moderno scenario della Sanità Pubblica, l’Alfabetizzazione Sanitaria (Health Literacy, HL) si pone come un determinante fondamentale di salute e un indicatore critico della qualità dei sistemi assistenziali. L’Health Literacy è definita come l’insieme delle abilità cognitive e sociali che permettono agli individui di procurarsi, valutare e declinare correttamente le informazioni sanitarie, rappresentando la condizione necessaria attraverso cui i cittadini possono esercitare una reale autonomia decisionale nel proprio percorso di cura.
L’importanza di tale costrutto non risiede esclusivamente nella dimensione individuale, ma nella capacità del paziente di agire come partner attivo nel setting assistenziale. Una solida Health Literacy favorisce, infatti, un’alleanza terapeutica simmetrica tra utente e operatore, trasformando il processo comunicativo in un ambiente collaborativo e costruttivo. In quest'ottica, l’alfabetizzazione sanitaria smette di essere un obiettivo meramente educativo per diventare un asset strategico con impatti multidimensionali:
- clinici, riducendo l'incidenza di errori e complicanze;
- sociali, garantendo equità nell'accesso ai servizi;
- economici, ottimizzando l’allocazione delle risorse e riducendo gli sprechi derivanti da un uso improprio dei servizi.
Inoltre, dobbiamo notare che il focus si sta oggi spostando dalla responsabilità del singolo alla reattività del sistema attraverso il concetto di Organizational Health Literacy (OHL). Questo paradigma definisce il grado con cui le organizzazioni sanitarie riescono a semplificare l’accesso ai propri servizi, rendendo le informazioni comprensibili e fruibili a tutti i livelli di utenza. Il passaggio verso una struttura "alfabetizzata" richiede necessariamente un approccio multidisciplinare, capace di integrare la visione dei decision maker con la pratica clinica e il supporto delle figure amministrative e tecnologiche.
All’interno di questo percorso di transizione, la soddisfazione del paziente emerge non solo come parametro di qualità percepita, ma come vera e propria "porta d’ingresso" metodologica. Attraverso l'analisi dell'esperienza dell'utente, le organizzazioni possono identificare le barriere comunicative e strutturali, ponendo le basi per la progettazione di ospedali inclusivi e realmente incentrati sulla persona.
Per poter analizzare correttamente l’aspetto dell’OHL nel contesto italiano è stato realizzato uno studio con il due scopi:
- valutare la presenza e la conoscenza delle misure di OHL all’interno di 3 strutture ospedaliere, per avere una rappresentazione anche all’interno del servizio sanitario italiano;
- fornire un toolkit che comprenda strategie utili volte a migliorare o rafforzare l’HL all’interno di un’organizzazione sanitaria, utili sia in condizioni ordinarie che in contesti emergenziali.
MATERIALI E METODI
Lo studio, di tipo cross-sectional e aperto, è stato svolto presso tre strutture sanitarie del Centro e Nord Italia, scelte per determinate caratteristiche quali l’alta complessità assistenziale (con dotazione superiore ai 500 posti letto), la presenza di un Dipartimento Emergenza e Accettazione (DEA) di II livello, l’essere centri di riferimento regionali, oltre che per l’elevata qualità, secondo i criteri del Piano Nazionale Esiti (PNE), dell’assistenza incentrata sul paziente e l’integrazione tra assistenza clinica, formazione e ricerca, trattandosi di centri ospedalieri universitari.
È stato realizzato un questionario suddiviso in tre sezioni che miravano ad indagare le informazioni demografiche e professionali, la qualità percepita del servizio (valutata utilizzando la scala Quality-Oriented Climate and Service Quality (QO-CSQ)) e infine la presenza dei 10 attributi di un organizzazione sanitaria alfabetizzata tramite il questionario Health-Literate Healthcare Organization (HLHO-10), un questionario internazionale già tradotto e validato in lingua italiana, modificato per indagare tramite likert scale la presenza o assenza piuttosto che la frequenza di attributi all’interno dell’organizzazione. Inoltre, allo scopo di valutare la qualità del servizio offerto dall’ospedale di appartenenza del personale contattato, all’interno del questionario sono state inserite 12 ulteriori domande tratte dallo studio Romiti del 2016.
Per valutare la struttura dimensionale della scala HLHO-10, è stata condotta un’analisi fattoriale esplorativa (EFA) tramite Analisi delle Componenti Principali (PCA) con rotazione Quartimax e normalizzazione Kaiser. Allo stesso tempo, per verificare l’adeguatezza del campionamento, sono stati utilizzati i test di Kaiser-Meyer-Olkin (KMO) e di sfericità di Bartlett. La coerenza interna del questionario è stata valutata tramite l’indice alfa di Cronbach, considerando accettabili valori maggiori o uguali 0.7.
Le correlazioni tra HLHO e qualità percepita dell’assistenza non clinica sono state analizzate tramite Coefficiente di Spearman e test di Kruskal-Wallis, rispettivamente per variabili continue e categoriali.
Infine, per identificare i predittori della qualità percepita (QUAL), sono stati testati tre modelli di regressione lineare stepwise: il primo modello (Modello 1) che prendeva in considerazione variabili demografiche e contestuali; il secondo modello (Modello 2) che alle variabili demografiche e contestuali del Modello 1 aggiungeva anche HLHO_F1, componente del questionario HLHO-10 che riunisce sette item relativi a pratiche operative informative e comunicative; il terzo modello (Modello 3) che alle variabili del Modello 2 aggiungeva HLHO_F2, a sua volta componente del questionario HLHO-10 che riunisce tre item relativi all'orientamento delle direzioni strategiche verso i temi dell'alfabetizzazione sanitaria per quel che concerne la politica istituzionale e la formazione del personale.
RISULTATI
L’analisi dei questionari ha mostrato che la maggior parte dei rispondenti fosse di sesso maschile e con un’età media di 55.6 (SD = 8.9) anni. Per quanto riguarda gli aspetti di anzianità professionale, la durata media di lavoro nel settore sanitario è stata di 30.4 (SD = 9.2) anni con un’anzianità lavorativa nella struttura attuale media di 21.8 (SD = 11.1) anni e un’esperienza media in un ruolo dirigenziale di 13.6 anni (SD = 7.7). In riferimento alle due componenti HLHO-10, la prima (HLHO_F1) ha mostrato un punteggio medio più elevato rispetto alla seconda (HLHO_F2), rispettivamente 4.74 e 3.74, ma un indice di coerenza interna minore, rispettivamente di 0.887 e 0.922.
Inoltre, la correlazione per ranghi di Spearman ha rivelato che entrambe le componenti di HLHO erano positivamente associate a QUAL (per HLHO_F1: (ρ = 0.397, p = 0.003) e HLHO_F2: (ρ = 0.494, p < 0.001)).
Quest’ultima ha mostrato un punteggio medio di 4.81 (SD = 1.78) e una correlazione significativa con l'età degli intervistati (ρ = 0.374, p = 0.005), gli anni di esperienza professionale nel settore sanitario (ρ = 0.309, p = 0.023) e gli anni in una posizione manageriale (ρ = 0.295, p = 0.031). Inoltre, i test di Kruskal-Wallis hanno rivelato come i punteggi QUAL variassero significativamente in base al numero di personale gestito (p = 0.023) e alla frequenza del contatto diretto con i pazienti (p = 0.045), con punteggi QUAL maggiori tra coloro che gestivano team più ampi e che avevano un'interazione costante con i pazienti.
Per quanto riguarda i modelli di regressione stepwise, per il Modello 1 solo il numero di personale gestito è risultato un predittore significativo di QUAL (β = 0.287, p = 0.041). Per il Modello 2, la componente HLHO_F1 è emersa come predittore statisticamente significativo (β = 0,325, p = 0.016), mentre la significatività predittiva del numero di personale è diminuita. Infine, nel Modello 3 la componente HLHO_F2 è risultata come il predittore più forte (β = 0.377, p = 0.004), mentre la componente HLHO_F1 ha perso significatività statistica (β = 0.204, p = 0.114).
CONCLUSIONI
In conclusione, mentre l’alfabetizzazione sanitaria organizzativa deve essere integrata nei processi strategici, formativi e decisionali, per superare la frammentazione e le pratiche isolate, appare evidente che i dirigenti di medio livello, grazie alla loro posizione operativa e gestionale, risultino la figura cruciale per convertire gli obiettivi dell’HL in pratiche concrete e risolvere le criticità comunicative. Allo stesso tempo anche i servizi di front-office e relazione con il pubblico rappresentano un elemento fondamentale nell’adeguata gestione del paziente, e di conseguenza una maggiore integrazione dell’HL in questi servizi migliora l’esperienza del paziente e la performance istituzionale
Infine, il nostro studio evidenzia la necessità di riconoscere l’OHL come componente strutturale dell’assistenza per affrontare i bassi livelli di HL in Italia, promuovendo chiarezza, accessibilità e coinvolgimento a tutti i livelli sanitari.INTRODUCTION
In the contemporary public health paradigm, health literacy (HL) is a pivotal determinant of health and a critical indicator of the quality of healthcare systems. Health literacy is defined as the set of cognitive and social skills that enable individuals to obtain, evaluate, and correctly interpret health information. It is the necessary condition through which citizens can exercise real decision-making autonomy in their own care pathway.
The significance of this construct is twofold: firstly, in terms of the individual dimension, and secondly, in terms of the patient's ability to act as an active partner in the healthcare setting. A solid health literacy promotes a symmetrical therapeutic alliance between the user and the operator, transforming the communication process into a collaborative and constructive environment. From this perspective, health literacy can no longer be regarded as a purely educational goal, but rather as a strategic asset with multidimensional impacts:
The clinical aspect is concerned with the reduction of errors and complications.
The overarching objective is to ensure social equity in access to services.
The objective is to optimise the allocation of resources and reduce waste resulting from the misuse of services, thereby achieving economic efficiency.
It is also important to note that the focus is now shifting from individual responsibility to system responsiveness through the concept of Organizational Health Literacy (OHL). This paradigm delineates the extent to which healthcare organisations are able to facilitate simplified access to their services, rendering information comprehensible and utilizable across all user levels. The transition to a "literate" structure necessitates a multidisciplinary approach, capable of integrating the vision of decision makers with clinical practice and the support of administrative and technological figures.
A study was conducted with two objectives in order to correctly analyse the aspect of OHL in the Italian context.
The objective of this study is to assess the presence and awareness of OHL measures within three hospitals, with a view to obtaining a representation of these measures within the Italian health service.
The provision of a toolkit is proposed, which would include a range of useful strategies. The aim of these strategies would be to improve or strengthen HL within a healthcare organisation. It is important to note that these strategies would be useful in both ordinary conditions and in emergency contexts.
MATERIAL AND METHODS
The cross-sectional, open study was conducted at three healthcare facilities in central and northern Italy. These were selected on the basis of specific characteristics, including the provision of high complexity of care (with a minimum of 500 beds), the presence of a Level II Emergency and Admissions Department (EAD), and their status as regional reference centres. Additionally, the study sites were chosen for their high quality, as determined by the criteria of the National Outcomes Plan (PNE), in the domains of patient-centred care and the integration of clinical care, training, and research. This selection criterion was particularly relevant given that the study sites are university hospitals.
A questionnaire was developed, comprising three sections. The first section sought to ascertain demographic and professional information. The second section utilised the Quality-Oriented Climate and Service Quality (QO-CSQ) scale to assess perceived service quality. The third section addressed the presence of the 10 attributes of a health-literate organisation. This section employed the Health-Literate Healthcare Organization (HLHO-10) questionnaire, an international questionnaire that had been translated and validated in Italian. The HLHO-10 questionnaire was modified to investigate the presence or absence of attributes within the organisation, rather than their frequency. This investigation employed Likert scales. Furthermore, in order to assess the quality of the service offered by the hospital to which the contacted staff belonged, 12 additional questions from the 2016 Romiti study were included in the questionnaire.
In order to evaluate the dimensional structure of the HLHO-10 scale, an exploratory factor analysis (EFA) was conducted. To this end, Principal Component Analysis (PCA) with Quartimax rotation and Kaiser normalisation were utilised. Concurrently, Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests were employed to ascertain the adequacy of the sampling. The internal consistency of the questionnaire was assessed using Cronbach's alpha index, with values greater than or equal to 0.7 being considered acceptable.
The correlations between HLHO and perceived quality of non-clinical care were analysed using Spearman's coefficient and Kruskal-Wallis tests for continuous and categorical variables, respectively.
In conclusion, in order to identify predictors of perceived quality (QUAL), three stepwise linear regression models were tested. The first model (Model 1) took into account demographic and contextual variables. The second model (Model 2) added HLHO_F1, a component of the HLHO-10 questionnaire that brings together seven items related to informative and communicative operating practices, to the demographic and contextual variables of Model 1. The third model (Model 3) added HLHO_F2, also a component of the HLHO-10 questionnaire, which brings together three items relating to the orientation of strategic directions towards health literacy issues in terms of institutional policy and staff training, to the variables in Model 2.
RESULTS
A thorough analysis of the completed questionnaires revealed that the majority of respondents were male, with an average age of 55.6 years (SD = 8.9 years). In terms of professional seniority, the average length of service in the healthcare sector was 30.4 years (SD = 9.2) years, with an average length of service in the current facility of 21.8 years (SD = 11.1) years and an average length of service in a managerial role of 13.6 years (SD = 7.7).
In relation to the two HLHO-10 components, the first (HLHO_F1) demonstrated a higher mean score than the second (HLHO_F2), with values of 4.74 and 3.74, respectively. However, the internal consistency index was lower for the first component (0.887) compared to the second (0.922).
In addition, Spearman's rank correlation indicated a positive association between both HLHO components and QUAL (for HLHO_F1: (ρ = 0.397, p = 0.003) and HLHO_F2: (ρ = 0.494, p < 0.001)).
The latter demonstrated an average score of 4.81 (SD = 1.78) and a significant correlation with the age of the respondents (ρ = 0.374, p = 0.005), years of professional experience in the healthcare sector (ρ = 0.309, p = 0.023), and years in a managerial position (ρ = 0.295, p = 0.031). Furthermore, Kruskal-Wallis tests revealed that QUAL scores varied significantly based on the number of staff managed (p = 0.023) and the frequency of direct contact with patients (p = 0.045), with higher QUAL scores among those who managed larger teams and had constant interaction with patients.
In relation to stepwise regression models, Model 1 revealed that the number of staff managed was the only significant predictor of QUAL (β = 0.287, p = 0.041). For Model 2, the HLHO_F1 component was identified as a statistically significant predictor (β = 0.325, p = 0.016), while the predictive significance of the number of staff members was found to decrease. In Model 3, the HLHO_F2 component emerged as the most robust predictor, with a beta coefficient of 0.377 and a p-value of 0.004. Conversely, the HLHO_F1 component exhibited a diminished statistical significance, with a beta coefficient of 0.204 and a p-value of 0.114.
CONCLUSIONS
In conclusion, while organizational health literacy must be integrated into strategic, training and decision-making processes in order to overcome fragmentation and isolated practices, it is clear that middle managers, thanks to their operational and managerial position, are crucial figures in converting health literacy (HL) objectives into concrete practices and resolving communication issues. Concurrently, front-office and public relations services represent a pivotal component in the effective management of patients. Consequently, enhanced integration of HL into these services has been demonstrated to improve the patient experience and institutional performance.
The present study underscores the necessity to acknowledge OHL as an integral component of healthcare, with the objective of addressing the suboptimal levels of HL prevalent in Italy. This approach emphasizes the promotion of clarity, accessibility, and involvement at all echelons of the healthcare system
Unveiling BYOVD Threats: Malware’s Use and Abuse of Kernel Drivers
No full textBring Your Own Vulnerable Driver (BYOVD) attacks abuse legitimate, digitally signed Windows drivers that contain hidden flaws, allowing adversaries to slip into kernel space, disable security controls, and sustain stealthy campaigns ranging from ransomware to state-sponsored espionage. Because most public sandboxes inspect only user-mode activity, this kernel-level abuse typically flies under the radar. In this work, we first introduce the first dynamic taxonomy of BYOVD behavior. Synthesized from manual investigation of real-world incidents and fine-grained kernel-trace analysis, it maps every attack to sequential stages and enumerates the key APIs abused at each step. Then, we propose a virtualization-based sandbox that follows every step of a driver's execution path, from the originating user-mode request down to the lowest-level kernel instructions, without requiring driver re-signing or host modifications. Finally, the sandbox automatically annotates every observed action with its corresponding taxonomy, producing a stage-by-stage report that highlights where and how a sample exhibits suspicious behavior. Tested against the current landscape of BYOVD techniques, we analyzed 8,779 malware samples that load 773 distinct signed drivers. It flagged suspicious behavior in 48 drivers, and subsequent manual verification led to the responsible disclosure of seven previously unknown vulnerable drivers to Microsoft, their vendors, and public threat-intelligence platforms. Our results demonstrate that deep, transparent tracing of kernel control flow can expose BYOVD abuse that eludes traditional analysis pipelines, enriching the community's knowledge of driver exploitation and enabling proactive hardening of Windows defenses
Understanding the role of Lacticaseibacillus rhamnosus in vaginal dysbiosis: in vitro studies and clinical evidence
No full textThis narrative review aims to analyze and describe the outcomes of the most recent in vivo and in vitro studies involving L. rhanmosus in vaginal dysbiosis. Vaginal dysbiosis affects many women around the world and antibiotic treatment could not be a long-term solution due to the emergence of multidrug resistant microrganism. Considering that, probiotic treatments could represent an innovative and integrative approach to restore healthy vaginal microbiota. The dominant microbial population associated with vaginal health is represented by Lactobacilli spp.. Among all the Lactobacillus species, an interesting role is played by L. rhamnosus, able to produce several metabolites with antimicrobial properties such as lactic acid, bacteriocines, hydrogen peroxide and a class of molecules named biosurfactants. The in vitro studies on the main pathogens of vaginal dysbiosis (G. vaginalis spp., Candida spp. and HPV, HIV) showed coherent scientific evidence on the inhibitory, immunomodulatory and gene expression alteration effects of L. rhamnosus strains. Moreover, the promising preliminary outcomes were confirmed by clinical trials on infected women suggesting L. rhamnosus could be an interesting treatment in defense, protection and restoring of healthy vaginal microbiota, supporting women health
Botulinum toxin for endometriosis-associated chronic pelvic pain: a randomised, double-masked, parallel, phase 2 trial
No full textBackground Chronic pelvic pain affects one in four women. Botulinum toxin, approved for chronic migraine and cervical dystonia pain, is an emerging treatment for other pain conditions. We evaluated intramuscular pelvic floor botulinum toxin injection in women with endometriosis-associated chronic pelvic pain and pelvic floor muscle spasm, hypothesising that botulinum toxin might reduce both spasm and pain. Methods In this a randomised, double-masked, parallel, phase 2 trial, women with pelvic floor spasm and pain despite standard endometriosis-specific and pain treatment were randomily assigned 1:1 to injection of 100 Units onabotulinumtoxinA (15 participants) or saline placebo (14 participants) into pelvic floor muscles. The primary outcome was patient report of benefit or no benefit assessed 1 month after masked injection. Patients could choose an open injection from 1 to 12 months after masked injection. Secondary outcomes (pain rating, pain medication usage, effect duration, and other participant-reported measures) were compared to baseline ratings. This study is registered with ClinicalTrials.gov, NCT01553201. Findings 29 participants were recruited between July 24, 2014 and May 8, 2018. All enrolled women completed the study. At 1 month, significantly more women in the toxin group reported benefit (11 (73%) of 15 vs 4 (29%) of 14; p = 0.027). Women receiving toxin attained a greater percent benefit (p = 0.034) and longer duration (p = 0.023) of pain relief. Those with at least moderate baseline pain had lower pain scores after toxin (p = 0.028). Benefit was present at 1 year in 16 of those requesting open injection (7 of 14 receiving placebo; 9 of 13 receiving toxin). 20 (77%) of 26 patients used less pain medication at 1-year (p < 0.0001), with 12 (92%) of 13 in the BoNT group and eight (62%) of 13 in the placebo group using less medication (p = 0.061). Adverse events were non-serious with no grade 3 or 4 adverse events or deaths, and were similar in both cohorts following masked and open injections. Interpretation This study demonstrates the efficacy and safety of pelvic floor botulinum toxin injection for women with endometriosis-associated chronic pelvic pain and pelvic floor spasm. Copyright Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)
Retrovation Typology: Exploiting and Exploring Past Knowledge for Nostalgic and Sustainable Innovation
No full textRetrovation, also known as retro-innovation, is an underexplored innovation process that has recently garnered increasing attention from researchers and companies. However, the literature is scarce and ambiguous, lacking a clear definition of the concept. Drawing on past knowledge, it is possible to give new life to updated products and technologies which can be re-diffused within specific cultural and market niches to originally develop nostalgic and sustainable solutions.
In this paper, based on a qualitative inductive study of different business projects applying past knowledge and adopting an entrepreneurial market-driven perspective, we propose an original typology of retrovation based on the market motivations behind the retrieval of the past knowledge (nostalgia versus sustainability) and the past knowledge reconfiguration process (exploitation versus exploration). While the market motivation can range from the most traditional driver of nostalgia to the emerging driver of sustainability, the reconfiguration process examines the extent to which companies must adapt past knowledge to make it suitable for modern markets. Through this framework, we contribute to the literature by identifying four distinct types of retrovation: revivification, reappropriation, revisitation, and regeneration. Finally, we suggest managerial implications to enable companies to better leverage the different types of retrovation
Gold-catalysed N-allenamide cyclisation as a platform for the construction of indole-fused quinoxaline and quinoline scaffolds
No full textWe report a gold-catalysed cyclisation of N-allenamides derived from 1- and 2-(2-aminoaryl)indoles, providing easy access to 5,6-dihydroindolo[1,2-a]quinoxalines and 6,11-dihydro-5H-indolo[3,2-c]quinolines. The reaction proceeds under mild conditions, tolerates diverse functional groups, and enables the synthesis of previously unexplored indole-fused heterocycles, whose versatility was demonstrated through selected post-functionalisation reactions
Neurodevelopmental effects of genetic frontotemporal dementia mutations revealed by total intracranial volume differences
No full textBackground: Converging evidence hints at neurodevelopmental effects in people at risk of genetic frontotemporal dementia (FTD). Objective: We investigated total intracranial volume (TIV), a neuroimaging marker of neurodevelopment, and years of education differences between adult mutation carriers and familial non-mutation carriers, as measures of the structural and functional neurodevelopmental effects of FTD-causing genetic mutations. Methods: This cross-sectional cohort study, facilitated through the FTD Prevention Initiative (FPI), included 902 adult pathogenic mutation carriers of GRN, MAPT, or C9orf72, and 532 familial non-carriers. ANCOVAs were computed to compare TIV and education between groups per gene. Pearson's correlations were used to examine associations between TIV and education. Results: Mutation carriers (mean ± SD age = 50.0 ± 13.2 years, sex = 55% female, n(GRN) = 298, n(MAPT) = 187, n(C9orf72) = 417) were compared to familial non-carriers (age = 48.0 ± 12.9 years, sex = 58% female, n(GRN) = 201, n(MAPT) = 114), n(C9orf72) = 217). Consistent with prior findings in young adults, GRN carriers showed larger TIV, on average by 20531 mm3, compared to familial non-carriers (95% CI [85.4, 40977], p = 0.049, η2p = 0.008). Larger TIV correlated with higher years of education in GRN carriers (95% CI [0.01, 0.24], r(295) = 0.12, p = 0.03) and GRN non-carriers (95% CI [0.08, 0.34], r(198) = 0.21, p = 0.002). MAPT carriers demonstrated smaller TIV than non-carriers, on average by 29896 mm3 (95% CI [–58248, −1545], p = 0.039, η2p = 0.02). Models with C9orf72 and education as outcome variables did not reveal significant differences. Conclusions: In support of the neurodevelopmental hypothesis of FTD, GRN and MAPT mutations are linked to structural neurodevelopmental changes in TIV. Further research is needed to identify mechanisms underlying neurodevelopmental influences of FTD mutations and ascertain their suitability as intervention targets
Impact of sex, age and body composition on rilpivirine and cabotegravir trough concentrations in people with HIV receiving long-acting injectable antiretroviral therapy
No full textBackground Considerable inter-individual variability in the pharmacokinetics of long-Acting injectable (LAI) rilpivirine and cabotegravir has been reported. Here, we sought to evaluate intra-and inter-individual variability of rilpivirine and cabotegravir plasma trough concentrations and to assess the influence of demographic factors and body composition on drug exposure in people with HIV (PWH) receiving LAI therapy. Methods This retrospective observational study included PWH treated with LAI rilpivirine and cabotegravir for ≥16 months, with at least three consecutive plasma trough concentration assessments. Body composition was estimated by bioelectrical impedance analysis. Associations between drug levels and clinical variables were analysed using univariate and multivariate regression analysis. Results Forty-eight PWH were included (mean age 47 ± 15 years, 17% females). Rilpivirine and cabotegravir showed moderate intra-individual variability in trough concentrations (28-30%), with <1% of samples below the therapeutic threshold. Cabotegravir trough concentrations were significantly higher in women than in men (3285 ± 921 versus 2096 ± 775 ng/mL; P < 0001) and in participants aged >65 years compared with younger individuals (2826 ± 455 ng/mL versus 2119 ± 1006 ng/mL; P = 0044); in addition, cabotegravir levels inversely correlated with skeletal muscle mass (r = -0.45; P = 0.008) and bone mass (r = -0.47; P = 0006). On the contrary, rilpivirine concentrations showed no significant associations with demographic or body composition variables. Multivariate analysis confirmed age, sex and muscle mass as independent predictors of cabotegravir exposure. Conclusions Sex, age and muscle mass significantly influence cabotegravir-but not rilpivirine-trough concentrations in PWH receiving LAI therapy. Therapeutic drug monitoring combined with body composition assessment may help to optimize dosing interval adjustment