Progressive multifocal leukoencephalopathy in a patient with Good's syndrome

Good's syndrome (GS) is an immunodeficiency characterised by thymoma, hypogammaglobulinemia and impaired T-cell function. The clinical symptoms are recurrent or chronic infections from common or opportunistic pathogens and diarrhoea. Encephalitis is rare, mostly associated to cytomegalovirus. We present a 65-year-old woman who developed blindness, motor deficits and cognitive changes over a 4-month period. MRI of the brain showed symmetric subcortical white matter changes in the occipital lobes, first thought to correspond to posterior reversible encephalopathy syndrome. A thymoma was found and operated. The patient had no B cells, low immunoglobulins and an inverted CD4/CD8 ratio. GS was diagnosed. In the cerbrospinal fluid >1  million JC virus copies/mL were found and a repeat MRI now showed a picture compatible with progressive multifocal leucoencephalopathy (PML). Her disease had a fatal outcome. The present case is the second reported association between GS and PML

A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota

Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM).Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing.Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis.Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota

Elucidating mechanisms of Gliomagenesis: Role of Glioma Stem Cells

I Gliomi Maligni rappresentano il tumore primitivo cerebrale pi\uf9 frequente nella popolazione adulta. Hanno inevitabilmente prognosi infausta ed i pazienti affetti da tale neoplasia rispondono solo minimamente ai diversi approcci terapeutici, che includono chirurgia, radioterapia e chemioterapie di prima e seconda linea. I gliomi maligni sono composti da una popolazione cellulare molto eterogenea, che include cellule con caratteristiche di staminalit\ue0. L\u2019acquisizione di tali caratteristiche contribuisce ai processi di gliomagenesi, di crescita tumorale e di resistenza alla terapia. Il presente lavoro \ue8 volto ad elucidare il ruolo del fattore di trascrizione MEF (myeloid Elf-1 like factor) nei gliomi. Abbiamo analizzato i livelli di espressione genica di MEF, riscontrando livelli molto alti in gliomi maligni umani e murini. L\u2019assenza del gene MEF in modelli murini sperimentali riduce la gliomagenesi. Nel presente lavoro abbiamo dimostrato come la modulazione dei livelli del gene MEF, sia in cellule staminali neurali di topo, sia in linee cellulari di gliomi umani, riduca significativamente la formazione di neurosfere. Inoltre, abbiamo identificato Sox2 come un downstream target diretto di MEF. Nell\u2019insieme, il presente studio indica il ruolo di MEF come un gene gatekeeper, precedentemente non riconosciuto, nel processo di gliomagenesi, in grado di promuovere caratteristiche di staminalit\ue0 attraverso l\u2019attivazione diretta di Sox2.High-grade gliomas (HGGs) represent the most frequent primary brain tumor in the adult population and inevitably have a dismal prognosis. Patients suffering from these type of tumor respond only minimally to therapies, including neurosurgery, radiation, first and second line chemotherapy. HGGs are composed of a heterogeneous population of cells that include many with stem-cell-like properties. The acquisition of stem-like traits has been described to contribute to glioma initiation, growth, and escape to therapies. Here we investigated the role of the transcription factor myeloid Elf-1 like factor (MEF, also known as ELF4) in gliomas. We found that MEF is highly expressed in both human and mouse glioblastomas and its absence impairs gliomagenesis in a PDGFdriven glioma mouse model. We show that modulation of MEF levels in both mouse neural stem cells and human glioblastoma cells has a significant impact on neurosphere formation. Moreover, we identify Sox2 as a direct downstream target of MEF. Taken together, our studies implicate MEF as a previously unrecognized gatekeeper gene in gliomagenesis that promotes stem cell characteristics through Sox2 activation

Building Sustainability in the Relationship with the Territory. The Cammino del Duca (the Duke’s Way) of the University of Urbino

In the last few decades, universities have experienced a growing integration with their local contexts, playing a fundamental role in urban and regional development processes. In such a context, new forms of convergence between the different missions of universities have also emerged in Italy, aimed at developing and co-creating sustainability in different dimensions through the involvement of local stakeholders. This article aims to highlight the driving role that universities can play in promoting sustainable local economies, moving from the example of the Cammino del Duca [Duke’s Way] – an itinerary defined and promoted by the University of Urbino Carlo Bo in collaboration with the local sections of the Italian Alpine Club (CAI), namely Montefeltro and Gubbio. In particular, this paper pays attention to the organizational process of the Cammino, highlighting its innovative aspects and unresolved critical issues to stimulate a reflection on opportunities and constraints affecting the sustainability policies of universities in interaction with local communities

Building Sustainability in the Relationship with the Territory. The Cammino del Duca (the Duke’s Way) of the University of Urbino

In the last few decades, universities have experienced a growing integration with their local contexts, playing a fundamental role in urban and regional development processes. In such a context, new forms of convergence between the different missions of universities have also emerged in Italy, aimed at developing and co-creating sustainability in different dimensions through the involvement of local stakeholders. This article aims to highlight the driving role that universities can play in promoting sustainable local economies, moving from the example of the Cammino del Duca [Duke’s Way] – an itinerary defined and promoted by the University of Urbino Carlo Bo in collaboration with the local sections of the Italian Alpine Club (CAI), namely Montefeltro and Gubbio. In particular, this paper pays attention to the organizational process of the Cammino, highlighting its innovative aspects and unresolved critical issues to stimulate a reflection on opportunities and constraints affecting the sustainability policies of universities in interaction with local communities

Murine adipose-derived mesenchymal stromal cell vesicles: in vitro clues for neuroprotective and neuroregenerative approaches

BACKGROUND AIMS: Adipose-derived mesenchymal stromal cells (ASC) are known to promote neuroprotection and neuroregeneration in vitro and in vivo. These biological effects are probably mediated by paracrine mechanisms. In recent years, nanovesicles (NV) and microvesicles (MV) have been shown to play a major role in cell-to-cell communication. We tested the efficacy of NV and MV obtained from ASC in mediating neuroprotection and neuroregeneration in vitro.METHODS: We exposed neuronal cells (both cell line and primary cultures) to oxidative stress in the presence or not of NV or MV.RESULTS: In this experimental setting, we found that low doses of NV or MV protected neurons from apoptotic cell death. We then assessed the neuroregenerative effect of NV/MV in cerebellar slice cultures demyelinated with lysophosphatidylcholine. We observed that low but not higher doses of NV and MV increased the process of remyelination and activated nestin-positive oligodendroglial precursors.CONCLUSIONS: Taken together, our data in vitro support the relevance of ASC vesicles as a source of protecting and regenerating factors that might modulate the microenvironment in neuro-inflammatory as well as in neurodegenerative disorders. The present findings may suggest that stromal cell-derived vesicles might represent a potential therapeutic tool, enabling the safe administration of stromal cell effector factors, avoiding the cellular counterpart

Il Cammino del Duca: un itinerario in costruzione tra università e territorio

Negli ultimi anni, le università italiane hanno conosciuto una crescente integrazione con i loro contesti di riferimento svolgendo un ruolo di fondamentale importanza nei processi di sviluppo urbano e regionale (Amato et al. 2006, Bagnasco 2004, Lazzeroni 2014). Questa accresciuta relazione con il territorio si inscrive dentro a trasformazioni di ampia portata e viene esercitata attraverso forme di collaborazione e di scambio con attori pubblici e privati nel tentativo di rispondere alle istanze che emergono dal livello locale (Emanuel 2019). I rapporti tra atenei e territori appaiono particolarmente rilevanti nelle periferie regionali, dato il loro potenziale generativo in termini di innovazione e attenuazione degli squilibri (Lazzeroni 2019). Nelle aree marginali simili collaborazioni tendono a conoscere una certa inclinazione in favore dello sviluppo turistico, ad esempio, mediante la condivisione di conoscenze e strumenti utili a definire progetti di valorizzazione delle specificità dei territori. Questo contributo intende sottolineare il ruolo promotore e trainante che può essere svolto dalle università nella realizzazione di itinerari “lenti”, evidenziando il metodo di costruzione e gli strumenti che l’Ateneo di Urbino sta proponendo, a partire da ottobre 2020, in collaborazione con le Sezioni CAI-Montefeltro e CAI-Gubbio, per la realizzazione del “Cammino del Duca”. Un Cammino che attraversa l’appennino umbro-marchigiano, configurandosi come un progetto di turismo sostenibile, coerente con la SNAI e funzionale alle missioni dell’Ateneo. La realizzazione del Cammino è accompagnata da approfondimenti teorici ed empirici relativi a: i) l’analisi del contesto per l’individuazione dei principali trend socio-economici negli ultimi anni; ii) lo studio delle relazioni tra perifericità territoriale, domande di riconoscimento (Carrosio 2020) e dinamiche di consenso/dissenso verso progetti volti alla sostenibilità ambientale; iii) la definizione/applicazione di un modello di valutazione dell’impatto economico e sociale del Cammino mediante indagini qualitative (focus group e interviste semi-strutturate a testimoni privilegiati) e quantitative (rilevazioni condotte tramite questionario). A tali attività si somma la sperimentazione del tracciato attraverso iniziative organizzate dall’Ateneo con l’obiettivo di raccogliere indicazioni dai partecipanti, che includono anche momenti di trasmissione di conoscenze scientifiche e di interlocuzione con le comunità locali, in un processo di “costruzione itinerante” che possa favorire la condivisione nonché l’individuazione di siti, risorse e narrazioni da valorizzare nel Cammino stesso