Alcohol consumption and autoimmune diseases

Alcohol is the second-most misused substance after tobacco. It has been identified as a causal factor in more than 200 diseases and 5.3% of all deaths and is associated with significant behavioral, social, and economic difficulties. As alcohol consumption may modulate the immune system's regulatory mechanisms to avoid attacking the body's tissues, it has been proven to play a dichotomic role in autoimmune diseases (ADs) based on the quantity of consumption. In this review, we report updated evidence on the role of alcohol in ADs, with a focus on alcohol addiction and the human biological immune system and the relationship between them, with alcohol as a risk or protective factor. Then, in this narrative review, we report the main evidence on the most studied ADs where alcohol represents a key modulator, including autoimmune thyroiditis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, diabetes, allergic rhinitis, and primary biliary cholangitis. Alcohol at low-moderate dosages seems mostly to have a protective role in these diseases, while at higher dosages, the collateral risks surpass possible benefits. The specific mechanisms by which low-to-moderate alcohol intake relieves AD symptoms are not yet fully understood; however, emerging studies suggest that alcohol may have a systemic immunomodulatory effect, potentially altering the balance of anti-inflammatory innate and adaptive immune cells, as well as cytokines (via the NF-κB or NLRP3 pathways). It might influence the composition of the gut microbiome (increasing amounts of beneficial gut microbes) and the production of their fatty acid metabolites, such as short-chain fatty acids (SCFAs) and polyunsaturated fatty acids (PUFAs), as well as elevated concentrations of acetate, high-density lipoprotein (HDL), and nitric oxide (NO). Unfortunately, a definite acceptable daily intake (ADI) of ethanol is complicated to establish because of the many mechanisms associated with alcohol consumption such that despite the interesting content of these findings, there is a limit to their applicability and risks should be weighed in cases of alcoholic drinking recommendations. The aim of future studies should be to modulate those beneficial pathways involved in the alcohol-protective role of ADs with various strategies to avoid the risks associated with alcohol intake

Immuno-metabolic and phenotypic characterization of autoimmune diabetes and its complications

Background and objectives. Latent autoimmune diabetes in adults (LADA) is marked by a slower decline in β-cell reservoir over time than early-onset, “classical” type 1 diabetes (T1D). The endogenous mechanisms that slow down the β-cell demise are unknown and barely investigated. This research appraisal is aimed at (1) investigating the autoimmunity against interferon (IFN)-α as a possible protective mechanism to distinguish LADA from classical T1D, and (2) evaluating whether residual secretion of C-peptide is related to better metabolic control and less glycemic variability in people with young-onset T1D. Materials and methods. To pursue the first aim, levels of autoantibodies against IFN-α (AAb-IFN-α) were measured using a cell-based approach in 41 subjects with LADA and in 90 subjects with T1D. The primary and secondary outcomes were the difference between LADA and T1D in the proportion of participants testing positive for AAb against ≥2 and against 3 IFN-α isoforms, respectively. To achieve the second aim, random C-peptide was measured in 61 subjects with duration of T1D <15 years and linked to two weeks of continuous glucose monitoring (CGM) data corresponding to the date of blood sampling. The primary outcome was the difference in C-peptide levels between participants with high time below range (TBR) (n=15) and those with lower TBR (n=45). Results. In the first study, 7 (17.1%) and 5 (12.2%) participants with LADA, and 3 (3.3%) and 0 participants with T1D showed positivity for AAb against ≥2 and 3 IFN-α isoforms (p=0.011, and p=0.0025, respectively). Among LADA-positive individuals, levels of AAb against IFN-α2 isoform were inversely correlated with glutamic acid decarboxylase antibodies (GADA) titers (rho= -0.513; p=0.025). In the second study, random C-peptide levels were significantly higher among participants in the low-TBR group than in the high-TBR group (52.9 [19.5-176.3] vs 21.0 [9.4-106.6] pmol/l p=0.03, SMD=0.4 Persistence of C-peptide was associated with improved CGM-metrics (p<0.05). In logistic regression analysis exploring the relationship between TBR and C-peptide, β-coefficient of the regressions was similar before and after correction for disease duration (p=0.72). Conclusions. This project provides the first evidence of endogenous anti-IFN-α reactivity as an autoimmune response in LADA, a slowly progressive form of autoimmune diabetes (AD). This response is less commonly observed in people with the rapidly progressive form of AD, representing an endogenous defensive response against the rapid β-cell decay and the early need for insulin treatment at diagnosis. Therapeutic approaches aimed at maintaining C-peptide secretion have the potential to improve glycemic outcomes in people with AD, ultimately ameliorating the patients’ quality of life

Spastin elevating approaches and their validation in a Drosophila melanogaster model for Hereditary Spastic Paraplegia type 4 (SPG4-HSP)

Hereditary spastic paraplegias (HSPs) are a group of motor neuron disorders characterized by progressive spasticity in the lower limbs due to axonal degeneration. The most common form of HSP is due to SPG4 gene haploinsufficiency. SPG4 encodes the microtubule severing enzyme, spastin. Although, there is no cure for SPG4- HSP, strategies to induce a spastin recovery are emerging as promising therapeutic approaches. Our study aims to identify the molecular pathway regulating the turnover of spastin protein. Here, we show that the DDB1-Cullin-4-Ring ubiquitin ligase complex (CRL4) regulates spastin stability. We have generated a Drosophila melanogaster model of SPG4 (Dm-SPG4), in which we achieved RNAi-mediated downregulation of spastin in different fly tissues. Spastin downregulation in flies causes defects in locomotor activity, which is associated with alterations of neuromuscular junction morphology and function. Genetic inhibition of the CRL4 complex significantly affects several of these SPG4-like phenotypes in flies We show that the RNAi- mediated downregulation of Cullin 4 reduces the locomotor defects observed in the Dm-SPG4 model and ameliorates the alteration of synapse morphology. The downregulation of Cullin 4 rescues spastin protein levels in the same fly model. As a proof of concept, we have also pharmacologically inhibited the CRL4 complex with NSC1892. NSC1892 treatment elevates spastin levels and rescues pathological phenotypes in flies. Similar results were observed in patient-derived cells. Taken together, these findings show CRL4 involvement in spastin turnover and suggest the possibility of novel therapeutic interventions through the modulation of CRL4 activity

Concatenation of Kerr solitary waves in ceramic YAG: application to coherent Raman imaging

A coherent concatenation of multiple solitary waves may lead to a stable infrared and visible broadband filament in a ceramic YAG polycrystal. This self-trapped soliton train is leveraged to implement self-referenced multiplex coherent anti-Stokes Raman scattering (SR-M-CARS) imaging. Simulations and experiments illustrating the filamentation process and the concatenation of focusing-defocusing cycles in ceramic and crystal YAG are presented. In addition, our simulations and experiments further examine the dependence of the filamentation onset location and supercontinuum (SC) generation upon peak input power. Understanding this dependence is key for the implementation of viable CARS imaging techniques, due to the comparatively exceptional ability of YAG to generate supercontinuum that can enable higher-sensitivity imaging without delay lines

Sustainability in public lighting: the methodology for identifying environmentally optimal solutions in replacement planning. A case study

The urban public lighting system plays a fundamental role in enhancing safety and shaping the nocturnal identity of the city. Efficient lighting is also a key factor in reducing energy consumption and lowering atmospheric emissions. In the context of sustainable development goals, increasing attention is being directed towards the energy, social, economic, and environmental benefits associated with the adoption of LED lighting systems. This paper aims to assess the environmental impacts of two different public outdoor lighting replacement planning scenarios. The methodology employed in this study calculates the environmental impacts using a life cycle approach, incorporating data from the Environmental Product Declarations (EPDs) of the lighting systems. It involves a systematic census and categorization of lighting fixtures based on their installation year to determine both their quantity and average efficiency. This methodology, applied to a case study, demonstrates that it is possible to reduce the CO2-equivalent emissions by approximately 7% depending on the technical and environmental performance of the fixtures and the timing of their replacements. These results provide a scientific foundation for supporting both the preparation of planning tools by governance entities and the technical and economic feasibility of designing and implementing interventions aimed at improving the environmental performance of public lighting. These efforts could contribute to achieving climate neutrality, conserving biodiversity, and mitigating the effects of climate change

Low-Frequency Measurement of Moistened Wood-Based Materials

This article examines how water content is a crucial parameter for the preservation of wooden artworks and buildings, focusing on non-invasive ways of measuring water content through capacitive methods. A personalized, low-cost probe to measure the dielectric properties of oak and poplar wood at various water content levels and frequencies is described. The accuracy of the probe is confirmed by testing it with reference materials like air, PTFE, PLA, glass and Bakelite, demonstrating an accuracy error below 2%. Next, the probe is used to evaluate the relationship between water content and permittivity, indicating possible uses in conservation projects. Measurements were conducted on two types of wood, poplar and oak, at five varying levels of water content. The dielectric permittivity between 10 and 100 kHz was assessed. Using the vertical shift from the single interpolant of the dataset, a graduation curve was estimated. Finally, an R2 = 0.98 value demonstrates that a sigmoidal function reflects the relationship between the percentage water content and the permittivity of materials

Il ruolo del tecnostress nel benessere del lavoratore: un'analisi multidimensionale degli impatti organizzativi e sanitari nel settore ICT

In un mondo altamente globalizzato e tecnologico, il lavoro è protagonista di uno scenario sfidante e in continua trasformazione. In particolare nel settore ICT, l’innovazione continua, i processi complessi ed i rapidi cambiamenti espongono i lavoratori a fattori di stress che si sommano alle criticità normalmente presenti nell’ambiente professionale. Il sovraccarico di lavoro, la mancanza di chiarezza sulle mansioni, le difficoltà nelle relazioni interpersonali, le incertezze sul proprio ruolo e sulle competenze, sintetizzano il concetto di tecnostress e rappresentano gli elementi chiave per comprenderne le cause, le conseguenze e le possibili soluzioni. Attraverso un’analisi multidimensionale la ricerca esplora il fenomeno del tecnostress ed il suo impatto sul benessere del lavoratore e sulla produttività delle organizzazioni. Una revisione delle evidenze presenti in letteratura offre un punto di partenza per descrivere lo stress lavorativo ed i relativi strumenti di valutazione, il tecnostress e i potenziali impatti sulla salute psico-fisica degli individui. Vengono riportati poi i risultati di due studi osservazionali che indagano gli effetti del tecnostress sulla produttività di un’azienda ICT e il ruolo delle variabili organizzative e il tipo di attività nel determinare i livelli di stress dei lavoratori. Infine vengono riportati i risultati preliminari di un approccio qualitativo, basato sull’applicazione del focus group, per derivare rilievi soggettivi sulle esperienze dei dipendenti in rapporto allo stress percepito nel proprio ambiente di lavoro. Tramite un approccio integrato vengono dunque descritte le evidenze oggettive e soggettive correlate al fenomeno, raffrontate con quelle già riconosciute nel panorama scientifico, e utilizzate come riferimento per conoscere il problema e proporre modelli e soluzioni per contrastarlo. La ricerca sottolinea la necessità per le organizzazioni di adottare strategie di mitigazione del tecnostress, quali la promozione di modelli di lavoro flessibili e di un sano equilibrio vita-lavoro, la formazione continua per l’aggiornamento delle competenze tecnologiche e programmi di supporto psicologico per i dipendenti, al fine di sostenere ambienti di lavoro orientati alla produttività, alla resilienza organizzativa ed al benessere dei professionisti

In tempo di crisi. Note su Paolo III, gli ebrei e la questione ebraica nella prima metà del cInquecento

This article deals with the complicated dynamics of Pope Paul III’s relationship with the Jews and Judaism. In the first part, I provide a comprehensive overview of the historiography about his attitude towards the Jews. On the one hand, Paul III acted as a tolerant pope who protected prominent Jewish scholars and financiers such as Jacob Mantino. On the other hand, as the Pope of the Counter-Refor- mation, he adopted an intolerant stance by initiating the establishment of the House of Catechumens, persecuting converts, reviving the aggressive Roman Inquisition and introducing the Tridentine Council. Despite this apparent contradiction, I argue in the second part that Farnese’s various approaches to the Jews should be seen as an integral part of Paul III’s overarching political and ideological strategy, which both the Papal States and the Catholic Church pursued during the crisis of the 16th century

Supply Chain Management e Finanza per la Valorizzazione del Potenziale Sinergico delle Relazioni di Filiera verso la Sostenibilità

L’analisi della solidità finanziaria di un’impresa deve necessariamente includere la gestione della supply chain, considerata un asset strategico capace di generare valore competitivo. L’integrazione tra Supply Chain Management (di seguito anche "SCM") e finanza consente di valutare l’impatto economico-finanziario delle decisioni operative, migliorando la gestione del rischio e delle opportunità lungo la filiera. Tuttavia, gli approcci tradizionali trascurano spesso la correlazione tra performance logistiche e finanziarie, limitando le potenzialità aziendali. In tal senso, la Supply Chain Finance (di seguito anche "SCF") rappresenta una soluzione per ottimizzare il capitale circolante, rafforzando la resilienza e la competitività, in particolare per le PMI, che spesso incontrano ostacoli nell’accesso al credito. Con l’aumento dell’attenzione ai criteri ESG, si afferma la Sustainable Supply Chain Finance (SSCF), che promuove investimenti sostenibili e responsabili. In questo contesto, strumenti digitali innovativi supportano la misurazione delle performance ESG e la valutazione del potenziale di crescita delle imprese nella filiera. Inoltre, normative europee come la CSRD e la CSDDD impongono maggiore trasparenza nella supply chain, coinvolgendo anche le PMI, che devono affrontare i costi di conformità e la transizione ecologica. Un ruolo centrale è svolto dalla funzione approvvigionamenti, evoluta da attività amministrativa a leva strategica. Oggi le imprese riconoscono i fornitori come partner strategici, capaci di migliorare la qualità e le prestazioni del prodotto finale. Tuttavia, molte aziende adottano ancora un approccio tradizionale, focalizzato sulla riduzione dei costi piuttosto che su innovazione e sostenibilità. Per massimizzare il valore della supply chain, è essenziale un modello di gestione dei fornitori basato su tre livelli di integrazione: operativa, prestazionale e strategica. La collaborazione tra settore finanziario e industriale, unita all’adozione di strumenti innovativi, è cruciale per promuovere modelli di crescita sostenibile e rafforzare la competitività delle imprese

Optical applications of Terahertz/Infrared spectroscopy for the detection of biomolecules

Biomedical and biophysical science is one of the most significant research fields in the 21st century. Several techniques are used for studying biomolecules dynamics and biosystems (generally not in their physiological environment), e.g., magnetic resonance, fluorescence imaging techniques, vibrational and acoustics spectroscopy and biochemical assays. Among them, one of the most important technique is the Terahertz Infrared (THz/IR) spectroscopy. This PhD project proposes the design and the development of a TH z/IR spectroscopic platform and a novel methodological approach for the detection and study of biomolecules of biological relevance and biosystems. The project is divided in different tasks, as follows (i) Design and Development of a THz /IR spectroscopy setups , (ii) evaluation of its performances, (iii) conceptualization and comparison of THz/IR spectroscopy for biomolecules and biosystems of interest