Fungal endogenous endophthalmitis secondary to magnusiomyces capitatus

We report the case of a 68-year-old immunocompetent patient with a dilatation of the ascending aorta, intraluminal vegetations, and pseudoaneurysmatic bulging who presented with unilateral fungal endogenous endophthalmitis 8 days after coronary angiogram. The isolated pathogen resulted to be Magnusiomyces capitatus, a filamentous, yeast-like fungus that can be commonly found in normal human microflora, with an immunosuppression-related pathogenicity. A literature research revealed a single case of ophthalmic infection - a keratitis - caused by this pathogen. Furthermore, we add a review of mycotic endophthalmitis related to aortic infection

Convolutional neural network based on fluorescein angiography images for retinopathy of prematurity management

Purpose: The purpose of this study was to explore the use of fluorescein angiography (FA) images in a convolutional neural network (CNN) in the management of retinopathy of prematurity (ROP).Methods: The dataset involved a total of 835 FA images of 149 eyes (90 patients), where each eye was associated with a binary outcome (57 "untreated" eyes and 92 "treated"; 308 "untreated" images, 527 "treated"). The resolution of the images was 1600 and 1200 px in 20% of cases, whereas the remaining 80% had a resolution of 640 and 480 px. All the images were resized to 640 and 480 px before training and no other preprocessing was applied. A CNN with four convolutional layers was trained on 90% of the images (n = 752) randomly chosen. The accuracy of the prediction was assessed on the remaining 10% of images (n = 83). Keras version 2.2.0 for R with Tensorflow backend version 1.11.0 was used for the analysis.Results: The validation accuracy after 100 epochs was 0.88, whereas training accuracy was 0.97. The receiver operating characteristic (ROC) presented an area under the curve (AUC) of 0.91.Conclusions: Our study showed, we believe for the first time, the applicability of artificial intelligence (CNN) technology in the ROP management driven by FA. Further studies are needed to exploit different fields of applications of this technology.Translational Relevance: This algorithm is the basis for a system that could be applied to both ROP as well as experimental oxygen induced retinopathy

Survey on retinopathy of prematurity (ROP) in Italy

This study aims to investigate the incidence and the relative risk factors of retinopathy of prematurity (ROP) and posterior-ROP (P-ROP): ROP in Zone I and posterior Zone II, as well as to analyze the occurrence of surgical treatment of ROP and to evaluate the short term outcome of the disease in Italy

NANOASSEMBLATI DI AVIDINA E DNA COME STRUMENTI IN MEDICINA E DIAGNOSTICA

This work originates from the recent discovery of the existence in nature of a high-affinity interaction between avidin and nucleic acids wich can be guided to give rise to discrete and solution stable polyavidin nanoassemblies. The interest towards these systems is due to the fact that, since the latter are composed by many avidin units stably assembled, they can potentially be used in several biotechnological and biomedical applications as an improvement of the classic avidin-biotin system. The work herein described had a two-fold purpose: a) to deepen the knowledge about the molecular basis of the interaction between avidin and DNA and b) to evaluate the potential effectiveness of the nanoassemblies that arise from such interaction. The interaction between avidin and nucleic acids of different length, single and double stranded (plasmidic DNA, genomic DNA and synthetic oligomers) has been studied by using different analytical techniques, such as electrophoretic mobility assay, tryptophan fluorescence quench, HPLC and dynamic light scattering. The results provided clear indications on the size of the binding site, the mode of interaction with the different types of nucleic acids and their dissociation constants Kd. The results also provided valuable information to obtain optimized nanoassemblies formulations. ELISA and dot blot assays were performed to verify, in practical terms, the effective analytical performance of these nanoassemblies in in vitro diagnostic applications. The results showed the superiority of the nanoassemblies compared to the monomeric avidin. In addition, in view of a potential use as in vivo drug delivery and diagnostics tools, preliminary investigation on the in vivo biodistribution – conducted by means of fluorescence optical imaging – was carried out. The nanoassemblies are able to circulate in the blood stream for more than 72 hours and no preferential organ distribution was observed despite some liver accumulation.Questo lavoro origina dalla recente scoperta dell’esistenza in natura di una interazione ad alta affinità tra la proteina avidina e gli acidi nucleici e dal fatto che è possibile guidare tale interazione verso la formazione di nanoassemblati discreti e stabili. L’interesse verso questi sistemi deriva dal fatto che, in quanto costituiti da diverse unita’ di avidina unite assieme in modo stabile, essi possono potenzialmente trovare impiego in svariate applicazioni biotecnologiche e biomediche in analogia e come miglioramento del sistema avidina-biotina classico. Il lavoro descritto in questa tesi ha avuto un duplice obiettivo: approfondire le conoscenze relative alle basi molecolari dell’interazione tra avidina e DNA e al contempo valutare le effettive potenzialità in ambito applicativo dei nanoassemblati che originano grazie a tale interazione. Utilizzando diverse tecniche analitiche quali l’electrophoretic mobility assay, il quench della fluorescenza del triptofano, l’HPLC e il light scattering dinamico è stata studiata l’interazione tra avidina e acidi nucleici di diversa lunghezza (DNA plasmidico, DNA genomico, oligomeri sintetici) a singolo e doppio filamento. I risultati hanno fornito chiare indicazioni sulla dimensione del sito di binding, la modalità dell’interazione con le diverse tipologie di acidi nucleici e le relative costanti di dissociazione Kd. Lo studio dei meccanismi molecolari alla base dell’interazione tra la proteina e gli acidi nucleici ha permesso di ricavare informazioni preziose per l’ottenimento di formulazioni ottimizzate di nanoassemblati. Con lo scopo di verificare in termini pratici le potenzialità in ambito diagnostico dei nanoassemblati avidina-DNA è stata valutata la loro performance analitica in saggi di tipo ELISA e dot blot. I risultati ottenuti hanno dimostrato in modo inequivocabile la superiorità dei nanoassemblati rispetto all’avidina monomerica. In vista di un potenziale utilizzo in vivo dei nanaoassemblati come strumenti in diagnostica e nel direzionamento di farmaci è stata effettuata una prima indagine sulla loro biodistribuzione mediante imaging ottico di fluorescenza. I nanoassemblati sono in grado di circolare nel torrente sanguigno per oltre 72 ore e, a parte un lieve accumulo a livello epatico, non risulta evidente una distribuzione preferenziale verso determinati organi

Optimized avidin nucleic acid nanoassemblies by a tailored PEGylation strategy and their application as molecular amplifiers in detection

Avidin was recently found to display the ability to interact with high affinity with nucleic acids. In this work, we investigated how this property is affected by the protein modification with poly(ethylene glycol) (PEG). More precisely, we studied the influence of the size and geometry of the polymer and of the mode of anchorage to the protein surface. To this end, we synthesized five PEG derivatives capable of PEGylating avidin either through covalent attachment to its lysine primary amines or by exploiting its biotin binding pockets. Several differently PEGylated avidin derivatives were then obtained, which were later tested for their affinity for plasmid DNA by means of the electrophoretic mobility assay. The results show that covalent PEGylation reduces the affinity for DNA in a dose-dependent manner, whereas PEG anchoring through the biotin binding sites does not, even when bulky and high MW biotin-PEG derivatives are used. We then investigated how the size and molecular weight of the biotin-PEG affects the solubility and stability of avidin-nucleic acid nanoassemblies in physiological buffer. Among the biotin-PEG derivatives synthesized in this work, the branched forms were more efficient in protecting particle surface and preventing their aggregation. Full nanoparticle solubility was achieved by saturating 30% of the biotin binding sites with a 2 x 5 kDa branched derivative. the optimized avidin nucleic acid nanoassemblies (ANANAS) were employed in a model analytical test where they showed at least 40-fold higher efficiency than monomeric avidin in recognizing biotinylated surface immobilized IgGs. The results pave the way toward the application of this novel nanosystem in biomedicine

NANOASSEMBLED COMPLEXES OF NUCLEIC ACIDS, AVIDIN AND POLYMERS, USE AND PREPARATION THEREOF

The present invention discloses new nanoassembled complexes consisting of a central nucleus formed by a high-affinity interaction from nucleic acids and avidin, wherein said nucleus is stabilized in aqueous solutions, even saline, and protected from further unspecific unwanted interactions by means of suitable polymeric agents capable to mask totally or partially the nucleus itself. The nanocomplexes obtained have been shown to be stable in aqueous solutions and to have nanoparticle features. In addition, the nano-complexes have shown characteristics useful for use in biotechnological field and in nanomedicine

The effect of Na2CO3, NaF and NH4OH on the stability and release behavior of sol-gel derived silica xerogels embedded with bioactive compounds

Stability, defined as the reproducible behavior of a device upon its storage, is an important issue in pharmaceutical formulation. Silica xerogels obtained through the sol-gel route are relatively new as matrices for the controlled release of drugs. In some cases, it was observed that their behavior changes upon storage, so that they cannot always be defined as "stable". This occurs especially when gel processing is performed at mild temperatures, a procedure that may have to be used to prevent degradation of the embedded drug. This work investigated the use of inorganic catalysts as potential xerogel stability inducers when gel curing by heating is not applicable. Three compounds known to accelerate sol-gel polymerization, namely ammonia, sodium fluoride and sodium carbonate, were introduced during the polymerization of low-temperature processed inorganic and organically modified gels, and the effect of each compound on xerogel stability and drug release was monitored. The use of carbonate leads to formulations with good retention properties, as opposed to ammonia and NaF, which lead to poorly retentive xerogels in accordance with their known ability to increase porosity. Ammonia was shown to be a poor stability promoter independently of gel composition, as opposed to fluoride and carbonate, which both displayed stabilizing properties in a dose-dependent manner. No correlation was found between xerogel stability and drug release properties. An attempt was also made to correlate stability data with polymerization rates and wet gel syneresis time evolution with the purpose of identifying one or more synthesis parameters that could act as stability predictors for pre-formulation studies. No correlation was found between stability and syneresis data. A similar trend in the curve of gel time vs. catalyst concentration was observed for the two stabilizing catalysts, which was different for the non-stabilizing ammonia. It was concluded that the trend of this curve could potentially provide an indicator of catalyst stabilizing efficacy