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Sequential biostimulation and bioaugmentation treatments of a diesel-contaminated soil: effect on hydrocarbon degradation and soil bacterial communities
No full textBioremediation is considered a safe, economical and environmentally friendly approach for the treatment of contaminated soils. In this study, two aerobic biostimulation processes, landfarming (LF) and bioventing (BV), associated with nutrient addition (N) and followed by bioaugmentation (BA), were compared to assess the remediation of a contaminated soil. The experimental study was conducted over a 180-day period, with 120 days of biostimulation followed by 60 days of bioaugmentation, with a selected consortium of hydrocarbon (HC) degrading Actinobacteria, for 60 days. Microbiological analyses were carried out to characterize the diversity and composition of the microbial communities by cultivation on HC, and by 16S rDNA Illumina-MiSeq sequencing. Total petroleum HC (TPH), measured by Gas-Chromatography FID, was progressively reduced up to 40.8% in the LFNBA microcosm, after 180 days of landfarming and nutrient biostimulation followed by bioaugmentation. The quality of the treated soil was assessed by a phytotoxicity test that confirmed a progressive reduction of phytotoxicity. The contaminated soil was dominated by Acidobacteria, Actinobacteria, and Alphaproteobacteria. HC degrading bacteria were isolated and identified by 16S rDNA sequencing. After 180 days of treatment, an increase of Actinobacteria, Alphaproteobacteria and Bacilli in BV microcosms was observed, while TM7-3 and Gammaproteobacteria phyla increased in LF treatment. More than 40% of the bacteria detected in LF and BV microcosms were affiliated to HC degrading genera. Molecular investigations confirmed the presence of the alkane monooxygenase encoding gene, alkB for alkane biodegradation. The achieved results showed the feasibility of biostimulation coupled with bioaugmentation for the removal of hydrocarbons in contaminated soils
Implementation of a clinical, nutritional and genetic-molecular pathway for the treatment of patients with phenylketonuria
No full textIl presente studio ha come obiettivo principale la caratterizzazione genetica di pazienti affetti da fenilchetonuria (PKU) o con diagnosi sospetta di iperfenilalaninemia (hyperphenylalaninemia - HPA). Le HPA sono un gruppo di disturbi metabolici rari a trasmissione autosomica recessiva caratterizzati dall'accumulo di fenilalanina (Phe), un amminoacido essenziale, a livello ematico a causa di difetti nell'enzima che la metabolizza (fenilalanina idrossilasi - PAH). L'iperfenilalaninemia è generalmente causata da varianti genetiche nel gene PAH, con conseguente riduzione o completa inibizione dell'attività dell'enzima e incremento dei livelli plasmatici di Phe. Per la caratterizzazione genetica dei pazienti, è stato utilizzato il sequenziamento Sanger, insieme alla tecnica Multiplex Ligation-dependent Probe Amplification (MLPA), con l’obiettivo di identificare le varianti patogenetiche responsabili della malattia. Un obiettivo cruciale dello studio è stato quello di individuare i pazienti eleggibili al trattamento farmacologico con sapropterina dicloridrato, un cofattore che può migliorare l'attività enzimatica residua in alcuni soggetti con determinate varianti genetiche. I risultati ottenuti hanno sottolineato l'importanza di un approccio personalizzato nella gestione della PKU. Infatti, l’attività enzimatica residua dipende da variabili biochimiche specifiche, come i livelli di fenilalanina (Phe) e del cofattore tetrahydrobiopterina (BH4). La risposta al trattamento con sapropterina si verifica solo in determinate condizioni biochimiche, evidenziando la necessità di una valutazione approfondita e personalizzata per ogni paziente. Sebbene la PKU sia una malattia rara, essa manifesta una significativa eterogeneità sia a livello clinico che molecolare, con una varietà di presentazioni e di risposte al trattamento. Attualmente, la dieta rimane il cardine della terapia della PKU, ma l'introduzione di opzioni farmacologiche e biotecnologiche innovative ha reso necessaria una continua revisione e ottimizzazione dei protocolli terapeutici. Questo studio contribuisce a migliorare la comprensione della PKU e ad affinare le strategie terapeutiche, promuovendo un approccio integrato che combini genetica, nutrizione e farmaci per il trattamento personalizzato dei pazienti.The primary objective of this study is to genetically characterize patients with phenylketonuria (PKU) or suspected hyperphenylalaninemia (HPA). HPA is a group of rare, autosomal recessive metabolic disorders characterized by abnormal accumulation of phenylalanine (Phe), an essential amino acid, in the blood, due to defects in the enzyme that metabolizes phenylalanine (phenylalanine hydroxylase - PAH). HPA is generally caused by genetic variants in the PAH gene, resulting in reduced or complete inhibition of the enzyme's activity and increased plasma Phe levels. Sanger sequencing, combined with Multiplex Ligation-dependent Probe Amplification (MLPA), was used to genetically characterize the patients, with the aim of identifying the pathogenic variants responsible for the disease. A key objective of the study was to identify patients eligible for pharmacological treatment with sapropterin dihydrochloride, a cofactor that can improve residual enzyme activity in some individuals with certain genetic variants.The results underscored the importance of a personalized approach to PKU management. Indeed, residual enzyme activity depends on specific biochemical variables, such as phenylalanine (Phe) and tetrahydrobiopterin (BH4) cofactor levels. Response to sapropterin treatment occurs only under certain biochemical conditions, highlighting the need for a thorough and personalized evaluation for each patient. Although PKU is a rare disease, it exhibits significant heterogeneity both clinically and molecularly, with a variety of presentations and responses to treatment. Currently, diet remains the cornerstone of PKU therapy, but the introduction of innovative pharmacological and biotechnological options has necessitated the continuous review and optimization of treatment protocols. This study contributes to a better understanding of PKU and to refine therapeutic strategies, promoting an integrated approach that combines genetics, nutrition, and medications for personalized patient treatment
Ruolo predittivo dosimetrico della parete vescicale nella radioterapia convenzionale della prostata: integrazione di intelligenza artificiale e modellizzazione statistica
No full textIntroduzione:La radioterapia (RT) rappresenta uno dei pilastri terapeutici nel trattamento del carcinoma della prostata. Nonostante i progressi tecnologici, la tossicità genitourinaria rimane una delle principali limitazioni cliniche, con impatto significativo sulla qualità di vita dei pazienti. L’identificazione di parametri dosimetrici affidabili e di modelli predittivi accurati è pertanto cruciale per una pianificazione terapeutica personalizzata.Obiettivi:Valutare il ruolo predittivo dei parametri dosimetrici della parete vescicale nella comparsa di tossicità urinaria acuta nei pazienti sottoposti a radioterapia convenzionale per carcinoma della prostata, integrando approcci di modellizzazione statistica e algoritmi di machine learning.Materiali e Metodi:Studio retrospettivo con analisi di dati clinici e dosimetrici, includendo metriche derivate da DVH e valutazione degli endpoint di tossicità urinaria (es. disuria e pollachiuria) secondo criteri standardizzati. Sono stati costruiti e valutati modelli statistici e modelli di machine learning; le performance sono state stimate tramite metriche quali sensibilità, specificità e AUC (ROC), con confronto tra modelli.Risultati:Sono stati identificati specifici parametri dosimetrici della parete vescicale significativamente associati alla comparsa di tossicità urinaria, in particolare disuria e pollachiuria a diversi gradi. Tali parametri si sono dimostrati predittivi del rischio di tossicità genitourinaria, confermando il ruolo della dosimetria della parete vescicale nella valutazione degli esiti clinici. L’impiego di approcci di machine learning è stato esplorato come strumento complementare nell’analisi predittiva.Conclusioni:L’analisi dosimetrica della parete vescicale e l’uso integrato di modellistica statistica e machine learning rappresentano un approccio utile per studiare e supportare la predizione della tossicità urinaria nella RT prostatica, con potenziali ricadute sulla personalizzazione del trattamento.Background:Radiotherapy (RT) is a well-established curative option for prostate cancer, yet genitourinary toxicity may affect treatment tolerance and quality of life. Identifying dosimetric predictors and developing reliable risk models are key steps toward more personalized treatment planning.Purpose:To investigate the predictive role of bladder wall dosimetric parameters for urinary toxicity in patients undergoing conventional radiotherapy for prostate cancer, integrating statistical modeling and machine learning approaches.Materials and Methods:A retrospective study analyzed clinical and dosimetric data, including DVH-derived metrics, and urinary toxicity endpoints (e.g., dysuria and pollakiuria) graded according to standardized criteria. Statistical models and machine learning approaches were developed and evaluated; performance was assessed using sensitivity, specificity, and ROC-AUC, including model comparisons.Results:Specific bladder wall dosimetric parameters were identified as significantly associated with the occurrence of urinary toxicity, particularly dysuria and pollakiuria at different grades. These parameters showed a predictive value for genitourinary toxicity, supporting the relevance of bladder wall dosimetry in outcome assessment. Machine learning approaches were explored as complementary tools within the predictive analysis framework.Conclusions:Bladder wall dosimetric analysis combined with statistical and machine learning modeling provides a framework to support urinary toxicity risk assessment in prostate radiotherapy and may contribute to treatment individualization
Armonie sovrane. Diletti e omaggi musicali per le regine di Napoli
No full textThe essay illustrates the musical activities associated with and promoted by the queens who sat on the throne of Naples between 1738 and 1860: Maria Amalia of Saxony, Maria Carolina of Austria, Julie Clary, Carolina Bonaparte, Maria Isabella of Spain, Maria Cristina of Savoy, Maria Teresa of Austria and Maria Sofia of Bavaria. Special attention is paid to the cantatas offered to them on the occasion of crucial events such as marriage and the birth of the heir to the throne
Laponite-based nano-emulsions of amazonian essential oils
No full textThis study investigated the behaviour of essential oil-in-water emulsions (O/W) containing Bursera graveolens, and Ocotea quixos essential oils. To enhance their topical administration and stability, Laponite (a synthetic, hectorite-like clay) was added at different concentrations to the continuous phase. All formulations were assessed in terms of time-stability, particle size, zeta potential, antioxidant activity, rheological properties, and in vitro cytotoxicity. Despite the excellent encapsulation capacity of essential oils, the addition of 3 % w/w Laponite accelerated emulsion instability at extreme conditions. In contrast, this inorganic ingredient significantly improved the rheological properties for topical administration. High-resolution transmission electron microscopy (HR-TEM) was used to characterize the morphology of the emulsions, showing a layer of Laponite particles around the essential oil droplets, a typical feature of Pickering emulsions. Cytotoxicity studies confirmed that O/W emulsions were not toxic for cells, a result strengthened by 3 % w/w of Laponite. In conclusion, O/W microemulsion from Bursera graveolens and Ocotea quixos essential oils proved stable and safe as topical formulations. Rheological performance and in vitro cytotoxicity can be modulated by the addition of Laponite, although its concentration must be optimised
Anaerobic breast abscess caused by Prevotella bivia in non-lactating woman: A case report with diagnostic and clinical implications
No full textBackground and Clinical Significance: Prevotella bivia is an anaerobic Gram-negative bacillus commonly associated with pelvic and genital tract infections. Its isolation from breast abscesses, particularly in nonpuerperal women, is extremely uncommon. Case presentation: We report a unique case of a 40-year-old non- lactating woman presenting with a recurrent right breast abscess. The pa- tient experienced three episodes over three years (2022–2025); only the fourth episode was microbiologically confirmed as being caused by P. bivia, identi- fied using MALDI-TOF MS. Antimicrobial susceptibility testing revealed resistance to ampicillin and susceptibility to amoxicillin/clavulanic acid and other agents. Conclusion: The case underlines the critical role of anaerobic cultures and advanced identification techniques in recurrent breast infections. Although microbiological confirmation was achieved only in the latest episode, the recurrent clinical picture suggests a difficult-to-culture microbial aetiology
Varieties of Vagueness, Fuzziness and a Few Foundational (and Ontological) Questions
No full textVagueness, under its many names and forms (unsharp predicates, uncertainty, approximate and/or incomplete/inexact reasoning, partial knowledge and incomplete information, approximation, and so on), pervades many scientific theories. As soon as vagueness is introduced in a theory, the need for control and for the design of efficient, quantitative methods to exert such control arises. Oddly, such urge is even more present in the very disciplines that could more easily displace it, namely Computer and Information Sciences
Telecoaching Interventions for People with Epilepsy: Enhancing Physical Activity and Quality of Life through Digital Health. A Systematic Review
No full textPeople with Epilepsy exhibit low levels of physical activity compared with the general population, despite evidence suggesting potential benefits for seizure control, physical fitness and psychosocial well-being. Persistent barriers such as fear of seizures, limited access to supervised programs, transportation difficulties, and time constraints contribute to sedentary behaviour. Telecoaching (TC), which delivers structured exercise programs through digital technologies, may help overcome these barriers. This systematic review aimed to evaluate the feasibility and potential effects of TC-based training physical activity interventions in individuals with epilepsy, focusing on adherence, QoL, physical fitness and psychological outcomes. A systematic search of PubMed, Web of Science, and Scopus identified 1086 records, of which 7 studies involving 342 participants met the inclusion criteria. Interventions included remotely delivered aerobic, resistance, flexibility, and combined exercise programs. Study quality ranged from “fair” to “good”. TC-based interventions were generally safe and feasible, with no major adverse events reported. Evidence suggest potential benefits for physical fitness and psychosocial outcomes, particularly in paediatric populations, although the limited number and heterogeneity of studies preclude definitive conclusions, especially regarding seizure-related outcomes. Future research should focus on standardized TC programs, long-term follow-up, and adequately powered randomized trials to confirm effectiveness and sustainability
METABOLIC MEMORY IN PIEDE DIABETICO (DFS): MODIFICHE EPIGENETICHE SULL'ESPRESSIONE DEI MICRO-RNA E DEI POLIMORFISMI A SINGOLO NUCLEOTIDE (SNP) IN UNA COORTE DI PAZIENTI CON PIEDE DIABETICO E CORRELAZIONE CON GLI INDICI DI DISFUNZIONE ENDOTELIALE ADIPO-INFIAMMATORIA
No full textBackgroundIl piede diabetico rappresenta una causa significativa di morbilità nei pazienti diabetici, con un’incidenza approssimativamente doppia rispetto ai pazienti senza ulcere del piede. La “memoria metabolica” rappresenta le modificazioni epigenetiche indotte dall’iperglicemia cronica, nonostante la successiva correzione dei livelli glicemici. Tali modificazioni epigenetiche sembrano perpetuare il danno causato da livelli di glucosio persistentemente elevati anche in loro assenza, agendo a diversi livelli e influenzando principalmente i processi molecolari coinvolti nella guarigione delle ulcere diabetiche.MetodiL’obiettivo di questo studio trasversale era analizzare una coorte di pazienti diabetici con e senza ulcere agli arti inferiori.Abbiamo esaminato gli effetti delle modificazioni epigenetiche sull’espressione dei miRNA 126, 305 e 217 e la frequenza dei polimorfismi a singolo nucleotide (SNP) dei geni che codificano per molecole infiammatorie (ad esempio IL-6 e TNF-alfa), nonché le loro correlazioni con i livelli sierici di molecole pro-angiogeniche (ad esempio eNOS, VEGF e HIF-1α), di diverse adipochine e con la disfunzione endoteliale, valutata in modo non invasivo mediante tonometria arteriosa periferica con iperemia reattiva.Tra marzo 2022 e marzo 2023 sono stati arruolati 110 pazienti: 50 pazienti diabetici con lesioni da piede diabetico, 40 pazienti diabetici senza complicanze ulcerative e 20 pazienti non diabetici come gruppo di controllo.RisultatiI soggetti diabetici con lesioni ulcerative agli arti inferiori hanno mostrato livelli più elevati di citochine infiammatorie, quali VEGF (191,40 ± 200 pg/mL vs 98,27 ± 56,92 pg/mL vs 71,01 ± 52,96 pg/mL; p = 0,22), HIF-1α (40,18 ± 10,80 ng/mL vs 33,50 ± 6,16 ng/mL vs 33,85 ± 6,84 ng/mL; p = 0,10) e Gremlin-1 (1,72 ± 0,512 ng/mL vs 1,31 ± 0,21 ng/mL vs 1,11 ± 0,19 ng/mL; p < 0,0005), rispetto ai soggetti diabetici senza ulcere agli arti inferiori e ai controlli sani.Inoltre, abbiamo osservato che miR-217-5p e miR-503-5p risultavano espressi rispettivamente 2,19 volte (p < 0,05) e 6,21 volte (p = 0,001) in più nei pazienti con piede diabetico rispetto ai controlli sani.I pazienti diabetici senza complicanze ulcerative agli arti inferiori mostravano un’espressione di miR-217-5p e miR-503-5p rispettivamente 2,41 volte (p = 0) e 2,24 volte (p = 0,029) superiore rispetto ai controlli sani.Infine, i pazienti diabetici con e senza complicanze ulcerative degli arti inferiori presentavano una maggiore espressione del polimorfismo VEGF C2578A CC (p = 0,001) e una ridotta espressione del polimorfismo VEGF C2578A AC (p < 0,005) rispetto alla popolazione di controllo sana.È stato inoltre osservato un aumento significativo dei livelli di Gremlin-1 nei pazienti con piede diabetico, suggerendo che questa adipochina infiammatoria possa rappresentare un potenziale marker predittivo per la diagnosi di piede diabetico.ConclusioniI nostri risultati evidenziano che i pazienti con piede diabetico presentano una predominante espressione del polimorfismo VEGF C2578A CC e una ridotta espressione dell’allele AC. Inoltre, è stata riscontrata una sovraespressione di miR-217-5p e miR-503-5p nei pazienti diabetici con e senza sindrome del piede diabetico rispetto ai controlli sani.Questi risultati sono in linea con quanto riportato in letteratura, che descrive la sovraespressione di miR-217-5p e miR-503-5p nel contesto del piede diabetico. L’identificazione di tali modificazioni epigenetiche potrebbe quindi risultare utile nella diagnosi precoce del piede diabetico e nel trattamento dei fattori di rischio; tuttavia, sono necessari ulteriori studi per confermare questa ipotesi.BackgroundDiabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximately twice that of patients without foot ulcers. “Metabolic memory” represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing.MethodsThe aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers.We examined the effects of epigenetic changes on miRNA 126, 305, and 217 expression and the frequency of the SNPs of genes encoding inflammatory molecules (e.g., IL-6 and TNF-alpha) and their correlations with serum levels of proangiogenic molecules (e.g., ENOS, VEGF and HIF-1alpha) and several adipokines as well as with endothelial dysfunction, assessed noninvasively by reactive hyperaemia peripheral artery tonometry.Between March 2022 and march 2023, 110 patients were enrolled into the study: 50 diabetic patients with diabetic foot injuries, 40 diabetic patients without ulcerative complications and 20 nondiabetic patients as the control group.ResultsDiabetic subjects with lower limb ulcerative lesions exhibited higher levels of inflammatory cytokines, such as VEGF (191.40 ± 200 pg/mL vs. 98.27 ± 56.92 pg/mL vs. 71.01 ± 52.96 pg/mL; p = 0.22), HIF-1alpha (40.18 ± 10.80 ng/mL vs. 33.50 ± 6.16 ng/mL vs. 33.85 ± 6.84 ng/mL; p = 0.10), and Gremlin-1 (1.72 ± 0.512 ng/mL vs. 1.31 ± 0.21 ng/mL vs. 1.11 ± 0.19 ng/mL; p < 0.0005), than those without lower limb ulcers and healthy controls. Furthermore, we observed that miR-217-5p and miR-503-5p were 2.19-fold (p < 0.05) and 6.21-fold (p = 0.001) more highly expressed in diabetic foot patients than in healthy controls, respectively. Additionally, diabetic patients without lower limb ulcerative complications showed 2.41-fold (p = 0) and 2.24-fold (p = 0.029) higher expression of miR-217-5p and miR-503-5p, respectively, than healthy controls. Finally, diabetic patients with and without ulcerative complications of the lower limbs showed higher expression of the VEGFC2578A CC polymorphism (p = 0.001) and lower expression of the VEGFC2578A AC polymorphism (p < 0.005) than the healthy control population. We observed a significant increase in Gremlin-1 levels in patients with diabetic foot, suggesting that this inflammatory adipokine may serve as a predictive marker for the diagnosis of diabetic foot.ConclusionsOur results highlighted that patients with diabetic foot showed predominant expression of the VEGF C2578A CC polymorphism and reduced expression of the AC allele. Additionally, we found an overexpression of miR-217-5p and miR-503-5p in diabetic patients with and without diabetic foot syndrome compared with healthy controls.These results align with those reported in the literature, in which the overexpression of miR-217-5p and miR-503-5p in the context of diabetic foot is reported. The identification of these epigenetic modifications could therefore be helpful in the early diagnosis of diabetic foot and the treatment of risk factors. However, further studies are necessary to confirm this hypothesis
L’applicazione (indiretta e diretta) del diritto internazionale dei diritti umani ai fini della determinazione della (il)legittimità di un ordine
No full textThe chapter examines the role of international human rights law in determining the ‘legitimacy’ of an order and, consequently, the need to implement it and the possibility of invoking the defence of fulfilling a duty in case of commission of crimes. It notes that, to this end, the contribution of international law is primarily indirect, since it often constitutes the basis for the choice to adopt criminal offences or regulatory provisions, which must be interpreted in accordance with the respective international obligations, the violation of which determines the illegality of the order. However, there are also possible cases of direct application of international norms, with the aim of supplementing the rule imposing a criminal command or the rule enshrining the defence of fulfilment of a duty