Paediatric gastric organoids as a tool for disease modelling and clinical translation

Purpose: Knowledge of gastric epithelial homeostasis remains incomplete, lacking human-specific models for study. This study establishes a protocol for deriving gastric epithelial organoids from paediatric gastric biopsies, providing a platform for modelling disease and developing translational therapies. Methods: Full-thickness surgical samples and endoscopic mucosal biopsies were obtained from six patients. Gastric glands were isolated by a chemical chelation protocol and then plated in 3D culture in Matrigel® droplets in chemically defined medium. After formation, organoids were passaged by single cell dissociation or manual disaggregation. Cell composition and epithelial polarity of organoids were assessed by bright field microscopy and immunofluorescence analysis, comparing them to native paediatric gastric tissue. Results: Gastric glands were successfully isolated from all six patients who were aged 4 months to 16 years. Gastric glands from all patients sealed to form spherical gastric organoids. These organoids could be passaged by manual disaggregation or single cell dissociation, remaining proliferative up to 1 year in culture. Organoids retained normal epithelial cell polarity, with the apical surface orientated towards the central lumen. Organoids expressed markers of mature gastric epithelial cell types, except for parietal cells. Conclusion: Gastric organoids can be reliably generated from paediatric biopsies and are a representative in vitro model for studying gastric epithelium

Primary human organoids models: Current progress and key milestones

During the past 10 years the world has experienced enormous progress in the organoids field. Human organoids have shown huge potential to study organ development, homeostasis and to model diseases in vitro. The organoid technology has been widely and increasingly applied to generate patient-specific in vitro 3D cultures, starting from both primary and reprogrammed stem/progenitor cells. This has consequently fostered the development of innovative disease models and new regenerative therapies. Human primary, or adult stem/progenitor cell-derived, organoids can be derived from both healthy and pathological primary tissue samples spanning from fetal to adult age. The resulting 3D culture can be maintained for several months and even years, while retaining and resembling its original tissue’s properties. As the potential of this technology expands, new approaches are emerging to further improve organoid applications in biology and medicine. This review discusses the main organs and tissues which, as of today, have been modelled in vitro using primary organoid culture systems. Moreover, we also discuss the advantages, limitations, and future perspectives of primary human organoids in the fields of developmental biology, disease modelling, drug testing and regenerative medicine

Sviluppo di tecniche di simulazione eterogenea funzionale e numerica applicate all’ingegneria di sistemi aeronautici

Questo studio illustra l’impiego del ‘Model Based Systems Engineering’ (MBSE), in cui strumenti di modellazione funzionale si integrano con modelli numerici, da tempo impiegati in progettazione, per la realizzazione di sistemi complessi. E’ analizzato un sistema antighiaccio aeronautico, sviluppato nell’ambito del progetto ‘CRYSTAL’. L’obiettivo è stato raggiunto collegando il gestore di requisiti IBM DOORS®, IBM RHAPSODY®, che opera in ambiente SysML, e SIMULINK® o DYMOLA®. L’interoperabilità è stata garantita dallo standard di connessione Functional Mock–up Interface (FMI), che ha permesso di validare il processo realizzando la cosiddetta ‘simulazione eterogenea’ di modelli funzionali e numerici integrati

La sindrome disesecutiva nel Mild Cognitive Impairment: aspetti clinici e possibilità riabilitative

Le disfunzioni esecutive sembrerebbero coinvolte nella progressione dal mild cognitive impairment (MCI) alla malattia di Alzheimer (AD). La Frontal Assessment Battery (FAB) costituisce uno strumento rapido e affidabile per studiare le funzioni esecutive ma raramente è stata utilizzata nel MCI. Scopo del presente lavoro è di esaminare con la FAB le funzioni esecutive in un gruppo di soggetti con MCI amnestico (aMCI) al fine di evidenziare precoci alterazioni e programmare un intervento ribilitativo mirato.Disorders of executive funcctions may involve in the conversion of mild cognitve impairment to Alzheimer desease. The Frontal Assessment Battery (FAB) is considered a quick and reliable tool to explore the executive functions but it is not often used in MCI. In this study we examined esecutive functions in aMCI group using the FAB to show early alterations and to the aim to program a specific training

Morfometria delle strutture del tronco encefalico in pazienti affetti da atassia spino-cerebellare tipo 2 (SCA 2): indicatore diagnostico e riabilitativo?

Nel nostro studio abbiamo esaminato le strutture del tronco encefalico con la RMN morfometrica in pazienti con SCA2 e ne abbiamo analizzato le relazioni con l’aspetto clinico. I pazienti con SCA2 mostravano una riduzione dell’area del ponte e dei peduncoli cerebellari medi rispetto ai controlli, ma un’area mesencefalica simile. L’area del ponte era inversamente correlata al numero di triplette CAG e direttamente correlata all’età di esordio della malattia. I nostri risultati indicano che la RMN morfometrica è uno strumento utile per determinare il grado di atrofia delle strutture del tronco encefalico nella SCA2.We examined the structures of brainstem with MRI voxel-based morphometry in patients with Spinocerebellar ataxia type 2 (SCA2) and investigated the relationships with clinical findings. SCA2 patients had significant smaller area of the pons as compared to controls, but similar midbrain area. Concerning the cerebellar peduncles, MCP was more involved than SCP in SCA2 patients. Area of the pons was inversely correlated to CAG repeats and directly correlated to the age at onset. Our results indicate that MRI morphometric analysis is a useful tool to assess atrophy of brainstem stuctures in SCA2 subjects

Approccio clinico e possibilità di trattamento nella SLA

Il seguente lavoro sottolinea l’importanza di un approccio multidisciplinare alla SLA, malattia degenerativa ad esito infausto. Viene rimarcato l’importanza del lavoro integrato tra le figure professionali che giocano un ruolo centrale nella gestione del paziente.This study underlines the importance of a multidisciplinar approach to SLA. The role of an integrated equipe is fundamental in the management of the patients with SLA

Ciprofloxacin releasing gellan gum/polydopamine based hydrogels with near infrared activated photothermal properties

In this work, with the aim to obtain a wound dressing hydrogel, an amine derivative of gellan gum was crosslinked in the presence of 4arm-polyethylenglycole-vinylsulfone. Through this easy and reproducible chemical procedure, a hydrogel with advanced elastic properties and hydrolytic resistance under physiological conditions was obtained. The incorporation of different quantities of polydopamine in the gelling solutions allows to obtain different hydrogels with marked photothermal properties when irradiated with a laser in the near infrared at 810 nm. The organic nanoparticles, reacting with the amino groups of the polysaccharide derivative, contribute to increase the storage moduli of the hydrogels. Ciprofloxacin was loaded into the hydrogel with higher amount of polydopamine and drug delivery experiments were performed to investigate the effect of irradiation on the antibiotic release profile. Antimicrobial studies, evaluated against S. aureus and P. aeruginosa, revealed that generated hyperthermia exerts a direct inhibition on the pathogens growth and, in the case of S. aureus, adjuvates the ciprofloxacin antimicrobial effect

Isolated adductor longus avulsion in a young semi-professional football player: Imaging contribution and therapeutic considerations

Adductor longus injuries are usually observed at the proximal musculo-tendinous junction, but isolated tendinous ruptures (i.e., avulsion) at the origin on the pubic bone are uncommon. In this article, we report a new case of isolated adductor longus avulsion that occurred in a young athlete and was treated with conservative therapy. An 18 years old semi-professional football player, in the attempt to reach the ball with his right leg, reported acute pain and functional limitation in his left adductor area. Clinical examination showed tenderness on palpation associated with mild swelling. Manual strength testing of adductor muscles showed weakness and elicited moderate pain in the proximal groin region near the pubic bone. The diagnostic evaluations (ultrasound [3-14 MHz linear probe] and magnetic resonance imaging [1.5 Tesla magnetic field]), performed a few days after the event, showed a complete isolated avulsion of the proximal adductor longus tendon associated with a fluid collection, with a gap of about 9.5 mm from its insertion on the pubic bone. Degenerative alterations (sub-chondral sclerosis, bone edema, erosions, cortical irregularities, calcifications) were found. These findings were crucial in the treatment choice because conservative management is suggested when the gap is below 1 cm and when no important displacement of proximal torn tendon's end at dynamic ultrasound is appreciated. A structured rehabilitation protocol was implemented, allowing the player to come back to his full athletic activity after 146 days. Return to play was allowed when several subjective and objective parameters were fully satisfied (full hip range of motion, pain-free football-specific activities, less than a 5%-10% difference in hip adduction strength between the injured and uninjured legs, advanced anatomical healing of the adductor longus tendon seen on diagnostic exams, and Hip And Groin Outcome Score [HAGOS] scores similar to baseline data). This case report emphasizes the importance of diagnostic imaging and clinical assessments in the management of an adductor longus avulsion with short retraction (about 1 cm). Both imaging techniques are non-invasive and without risks, allow contra-lateral examination and may guide in the treatment choice; moreover, they significantly influence the post-care approach by enabling to fine-tune a safe return to full athletic activity with minor re-injury rate. While US can be used as primary imaging modality, MRI offers a higher level of accuracy