Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes

Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications

Gait patterns in Prader-Willi and Down syndrome patients

<p>Abstract</p> <p>Background</p> <p>Prader-Willi (PWS) and Down Syndrome (DS) are two genetic disorders characterised by some common clinical and functional features. A quantitative description and comparison of their patterns would contribute to a deeper understanding of the determinants of motor disability in these two syndromes. The aim of this study was to measure gait pattern in PWS and DS in order to provide data for developing evidence-based deficit-specific or common rehabilitation strategies.</p> <p>Methods</p> <p>19 PWS patients (17.7-40 yr) and 21 DS patients (18-39 yr) were evaluated with an optoelectronic system and force platforms for measuring kinematic and kinetic parameters during walking. The results were compared with those obtained in a group of normal-weight controls (Control Group: CG; 33.4 + 9.6 yr).</p> <p>Results and Discussion</p> <p>The results show that PWS and DS are characterised by different gait strategies. Spatio-temporal parameters indicated a cautious, abnormal gait in both groups, but DS walked with a less stable strategy than PWS. As for kinematics, DS showed a significantly reduced hip and knee flexion, especially at initial contact and ankle range of motion than PWS. DS were characterised by lower ranges of motion (p < 0.05) in all joints than CG and PWS. As for ankle kinetics, both PWS and DS showed a significantly lower push-off during terminal stance than CG, with DS yielding the lowest values. Stiffness at hip and ankle level was increased in DS. PWS showed hip stiffness values close to normal. At ankle level, stiffness was significantly decreased in both groups.</p> <p>Conclusions</p> <p>Our data show that DS walk with a less physiological gait pattern than PWS. Based on our results, PWS and DS patients need targeted rehabilitation and exercise prescription. Common to both groups is the aim to improve hypotonia, muscle strength and motor control during gait. In DS, improving pelvis and hip range of motion should represent a major specific goal to optimize gait pattern.</p

Le grandi isole del Mediterraneo occidentale: Sicilia Sardinia Corsica

La sintesi proposta dell’archeologia della Sicilia romana, seppure all’interno di limiti tassativi previsti nel progetto editoriale della collana che la ospita, e di uno schema concepito per tutte le circoscrizioni dell’impero romano, ha dato per la prima volta l’opportunità di riconsiderare la provincia Sicilia secondo una visuale più ampia – quella appunto dell’Impero – in un’ottica necessariamente svincolata dal giudizio di valore (negativo, nella critica moderna) sul quadro dell’isola al confronto con il periodo pre-romano, da un lato, e la “rinascita” tardoantica, dall’altro. La Sicilia romana ha infatti risentito di un persistente pregiudizio storiografico, insito nella sua natura di regione dell’Italia ma al contempo da questa distinta (isola e provincia), sede prima dell’annessione all’impero di prestigiose realtà politico-culturali al cui studio si sono dedicate ben maggiori energie, mentre l’esame delle dinamiche ed esiti della provincializzazione restava per lo più vincolato ai clichés delle fonti letterarie (ovviamente poco interessate ai fenomeni di lunga durata e di scarso rilievo evenemenziale registrati dall’archeologia), trascurandosi i dati materiali e l’incidenza dei fattori della “romanizzazione”, nei termini complessi che l’indagine sulle altre realtà provinciali contribuisce a mettere in luce. Una riflessione criticamente aggiornata e l’accrescimento esponenziale dei dati archeologici forniti dalle indagini sul campo, in particolare dopo l’edizione nel 1990 della prima monografia sull’archeologia della Sicilia romana (limitata all’età imperiale) ad opera di Roger Wilson, hanno consentito di delineare un quadro nuovo, seppure “in fieri”, non solo delle conoscenze, assai più consistenti di quanto solo pochi anni prima non s’immaginasse, ma anche dei punti critici e delle prospettive di approfondimento demandate a future ricerche, finalmente orientate verso approcci più sistematici e pluralistici. Un dato di estremo rilievo è la possibilità, adesso, di articolare diacronicamente e sincronicamente i fenomeni, come appare nelle sezioni dedicate alla città e al territorio e allo sfruttamento delle risorse e alle attività produttive, che lasciano percepire la ricchezza di spunti per ulteriori indagini, ma anche alla variegata fisionomia culturale, degna di specifico interesse. A fronte di un’immagine statica e negativa del periodo provinciale, sotto il segno del regresso e, tutt’al più, della “fossilizzazione” di aspetti culturali risalenti alla fase preromana prima del “risveglio” nel IV secolo d.C., legato agli interessi del patriziato romano e al potenziamento dell’asse Roma-Africa (di cui è emblema la celebre villa di Piazza Armerina), un’analisi non preconcetta dei dati consente di cogliere invece una serie di dinamiche evolutive, con importanti momenti di svolta nella fase delle due prime guerre puniche, tra il tardo II e il primo terzo del I secolo a.C., sotto Augusto, di nuovo dall’avanzato I secolo d.C. e nell’età dei Severi, e infine nel Tardo Antico; e soprattutto una varietà e complessità di situazioni specifiche che rispondono a differenze di sostrati e dati economico-ambientali, a fattori politici e culturali che innescano fenomeni di adeguamento e linee di sviluppo materialmente percepibili, in relazione sia con l’Urbe e le sue classi dirigenti, sia con il contesto mediterraneo nelle cui reti di connettività s’inserisce l’isola, attraverso i suoi poli produttivi ed economico-culturali via via emergenti

Clostridium difficile: 18 months surveillance at the Niguarda Hospital - Milano

Clostridium difficile is currently one of the most common cause of diarrhea in hospitalized or residents in long term care institutions patients, symptoms of infection ranging from diarrhea to pseudo-membranous colitis and toxic megacolon.The disease is due to the production of enterotoxin A, cytotoxin B or binary toxin. The emergence of hypervirulent new strains showing a tcdC regulatory gene deletion (ribotype 027) has been observed in recent years. Stool or rectal swab specimens were screened using automated real-time multiplex PCR (GeneXpert, Cellbio) to detect the presence of toxins producing (B toxin, binary toxin and tcdC gene deletion) C. difficile. All positive samples were cultured in order to isolate the causing infection strains.The binary toxin and/or tcdC deletion producing strains were genotyped using Multilocus Sequence Typing (MLST). MLST compares the intragenic sequences of seven housekeeping genes and provides a unique combination of alleles; to each combination is then assigned a Sequence Typing (ST). In the period January 2010 – June 2011, 3681 samples from 2234 patients were analyzed. Four hundred seventy-three patients (21.2%) were positive for the presence of C. difficile, 34 (7.2%) of there were also positive for binary toxin and 3 were positive for the tcdC gene deletion (suspected C. difficile NAP027).All the strains having tcdC gene deletion, showes ST3 typing by MLST method.These strains were isolated during the same period. The three patiens were epidemiologically linked: the patient A was hospitalized in the same room of patient B, while patient C was managed by the same team care of patient A.The spread ofsuch C. difficile strains is at the present very low in Italy. Our data confirm the poor prevalence of ribotype NAP027 and the usefulness of a presumptive diagnosis to implement immediately appropriate control measures