Modulation of the intrinsic neuronal excitability by multifunctional liposomes tailored for the treatment of alzheimer’s disease

Purpose: Nanotechnologies turned out to be promising in the development of diagnostic and therapeutic approaches toward neurodegenerative disorders. However, only a very scant number of nanodevices until now proved to be effective on preclinical animal models. Although specific tests in vivo are available to assess the potential toxicity of these nanodevices on cognitive functions, those to evaluate their biosafety in vitro on neurons are still to be improved. Materials and methods: We utilized the patch-clamp technique on primary cultures of cortical neural cells isolated from neonatal rats, aiming to evaluate their electrical properties after the incubation with liposomes (mApoE-PA-LIPs), previously proved able to cross the blood\u2013brain barrier and to be effective on mouse models of Alzheimer\u2019s disease (AD), both in the absence and in the presence of \u3b2-amyloid peptide oligomers. Results: Data show a high degree of biocompatibility, evaluated by lactate dehydrogenase (LDH) release and MTT assay, and the lack of cellular internalization. After the incubation with mApoE-PA-LIPs, neuronal membranes show an increase in the input resistance (from 724.14\ub176 M\u3a9 in untreated population to 886.06\ub186 M\u3a9 in the treated one), a reduction in the rheobase current (from 29.6\ub13 to 24.2\ub13 pA in untreated and treated, respectively), and an increase of the firing frequency, consistent with an ultimate increase in intrinsic excitability. Data obtained after co-incubation of mApoE-PA-LIPs with \u3b2-amyloid peptide oligomers suggest a retention of liposome efficacy. Conclusion: These data suggest the ability of liposomes to modulate neuronal electrical properties and are compatible with the previously demonstrated amelioration of cognitive functions induced by treatment of AD mice with liposomes. We conclude that this electrophysiological approach could represent a useful tool for nanomedicine to evaluate the effect of nanoparticles on intrinsic neuronal excitability

Raman spectroscopy uncovers biochemical tissue-related features of extracellular vesicles from mesenchymal stromal cells

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSC) are emerging as valuable therapeutic agents for tissue regeneration and immunomodulation, but their clinical applications have so far been limited by the technical restraints of current isolation and characterisation procedures. This study shows for the first time the successful application of Raman spectroscopy as label-free, sensitive and reproducible means of carrying out the routine bulk characterisation of MSC-derived vesicles before their use in vitro or in vivo, thus promoting the translation of EV research to clinical practice. The Raman spectra of the EVs of bone marrow and adipose tissue-derived MSCs were compared with human dermal fibroblast EVs in order to demonstrate the ability of the method to distinguish the vesicles of the three cytotypes automatically with an accuracy of 93.7%. Our data attribute a Raman fingerprint to EVs from undifferentiated and differentiated cells of diverse tissue origin, and provide insights into the biochemical characteristics of EVs from different sources and into the differential contribution of sphingomyelin, gangliosides and phosphatidilcholine to the Raman spectra themselves

Students’ satisfaction and teaching efficiency of university offer

This study analyses the factors affecting students’ satisfaction with university experience, focusing on the aspects characterising the teaching efficiency of educational offer. For this purpose, organisation of teaching activities, available information, teaching materials, and other facilities offered to students to make their learning experience more successful, are considered as indicators of teaching efficiency. Our interest in this topic is justified by the importance that students’ satisfaction assumes, not only as indicator of the quality of educational services but also for its relationship with overall life satisfaction and subjective well-being. A structural equation model with latent variables is estimated by using survey and administrative data of the University of Pisa. Main findings seem to show that teaching efficiency has a positive effect on satisfaction and suggest that whenever it is inadequate, or at least, considered as such, students are less satisfied for their university experience. The effects of other factors on students’ satisfaction such as studies organisation, social capital and internship experience are also discussed

Nanotechnology advances towards development of targeted-treatment for obesity

Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modifcation or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specifcity and unsustainable weight loss efects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side efects, and enhanced efcacy. These efects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbiditie

Riflessioni e scoperte in tema di predittori di esito in psicoterapia : introduzione alla sezione speciale

La valutazione della efficacia delle psicoterapie nei Servizi Pubblici E. Fava, C. Masserini Paragrafo 1. Introduzione La valutazione del ruolo delle psicoterapie nel contesto dei servizi pubblici di salute mentale è un argomento complesso. Innanzi tutto nei servizi di salute mentale gli esiti sono il possibile prodotto di un insieme di interventi, più o meno integrati tra loro e di diverso genere, e non il prodotto di un singolo tipo di trattamento. E’ possibile, per esempio, che la presenza-assenza di un certo tipo di trattamento psicofarmacologico, riabilitativo o psicoterapico possa incrementare piuttosto che ridurre l’efficacia complessiva dell’intervento terapeutico. Fattori terapeutici di natura psicoterapeutica, cioè relazionale e cognitiva, possono inoltre essere attivi nel contesto di un intervento prevalentemente farmacologico e/o riabilitativo. Lo sviluppo di procedure terapeutiche efficaci e a costi contenuti è un’esigenza indifferibile e quindi uno stimolo per produrre ricerca sulle pratiche terapeutiche nei servizi di comunità. Non meno importante è il problema della generalizzazione dei risultati delle ricerche in contesti differenti da quelli in cui le ricerche sono state realizzate. Occorre sapere in che misura un trattamento che si è mostrato efficace in un contesto sperimentale o comunque selezionato è efficace anche nei servizi “veri”, cioè con pazienti, terapeuti e contesti di cura che possono essere differenti da quelli in cui le ricerche sono state condotte. La collaborazione e la conoscenza dei risultati delle ricerche da parte dei clinici è la condizione per cui la ricerca si trasformi in competenza a curare e in efficacia nella pratica quotidiana. Tuttavia non sempre i risultati delle ricerche sono percepiti come effettivamente utili da parte dei clinici e degli amministratori che dovrebbero metterli in atto. Questo in parte è dovuto ad un’effettiva inadeguatezza dei dati di cui disponiamo rispetto alle attese e alle domande dei clinici. Dopo gli studi d’efficacia e quelli in cui il processo terapeutico è stato studiato in generale, nuove prospettive di ricerca si sono focalizzate sui problemi che possono nascere nel corso di un trattamento e su quelli che si riferiscono a particolari categorie di pazienti