6 research outputs found
Triorchidism: genetic and imaging evaluation in an adult male
No full textWe report the results of imaging and
cytogenetic studies in a case of tri- orchidism in a 54 years old male without any associated
anomaly.
A scrotal ultrasonography revealed the presence of two testes within the left hemiscrotum with complete septa- tion and echotexture and vascular flow pattern similar to the vascular flow of the normal right testis.
There was no focal abnormal echogenicity suggesting malignancy. Scrotal MRI confirmed two soft-tissue structures in the left hemiscrotum with normal signal intensity at T1w and T2w images. Both testes had a tunica albuginea with low-signal intensity.
Cytogenetic analysis resulted in normal male karyotype 46XY. Array-CGH analysis detected the presence of two interstitial rearrangements: a ~120 Kb deletion of chro- mosome 1 and a ~140 Kb deletion of chromosome 16. Currently there are little details on the functions of both genes
PDMAEMA transfectants: impact of molecular weight and endosomal escape
No full textLAUREA MAGISTRALELo studio valuta l'efficacia del poli(2-(dimetilamino)etil metacrilato) (PDMAEMA) come vettore non virale per la veicolazione genica, concentrandosi sull'impatto del peso molecolare, dell'architettura chimica e delle condizioni sperimentali sull'efficienza di trasfezione e sulla citotossicità. Sono state sintetizzate diverse strutture di PDMAEMA, tra cui lineare (3,9 – 19,1 kDa), a stella (25 kDa) e copolimero con il policaprolattone (PCL). Le analisi comparative vengono eseguite con la poli(etilenimina) (25 kDa bPEI), considerata il gold standard di riferimento.
I risultati dimostrano che i polimeri ad alto peso molecolare forniscono una maggiore protezione e condensazione del DNA, migliorando l’efficienza di trasfezione; tuttavia, questo vantaggio è associato a un aumento della citotossicità, probabilmente dovuto a interazioni più forti con la membrana cellulare. Un aspetto critico analizzato in questo lavoro riguarda la capacità di eseguire la fuga endosomiale: il PDMAEMA mostra una capacità limitata nel favorire il rilascio del DNA dal compartimento endosomiale, un passaggio chiave per un’efficace trasfezione.
I risultati sperimentali dimostrano che l’applicazione di uno shock osmotico con soluzioni ipotoniche induce una maggiore permeabilizzazione endosomiale, determinando un miglioramento dell’efficienza di trasfezione fino a dieci volte maggiore. Questo approccio suggerisce che la manipolazione delle condizioni extracellulari possa rappresentare una strategia valida per superare le limitazioni del vettore.
In sintesi, i dati supportano l'ipotesi che una combinazione di PDMAEMA a basso peso molecolare con condizioni osmotiche controllate possa rappresentare un'alternativa efficace e meno citotossica rispetto ai vettori tradizionali. Studi futuri potrebbero approfondire le interazioni tra PDMAEMA e DNA, indagando la stabilità dei complessi formati, l’ottimizzazione della struttura del polimero ed eventuali strategie di fuga endosomiale per massimizzare l'efficienza della trasfezione.The present study investigated the efficacy of poly(2-(dimethylamino)ethyl methacrylate (PDMAEMA) as a non-viral gene delivery vector, with particular emphasis on how molecular weight (MW), chemical architecture, and experimental conditions influence transfection efficiency (TE) and cytotoxicity. Different formulations of PDMAEMA - including linear (3.9 – 19.1 kDa), star-shaped (25 kDa), and as a copolymer with polycaprolactone (PCL) - were synthesized. All formulations were benchmarked against the gold standard 25 kDa branched-polyethyleneimine (bPEI). Our findings demonstrate that high MW (HMW) polymers provide enhanced DNA protection and condensation, resulting in superior TE; however, this advantage is counterbalanced by increased cytotoxicity, presumably due to stronger interactions with cellular membranes. A significant challenge identified in this research concerns endosomal escape: PDMAEMA demonstrates limited capacity to facilitate DNA release from the endosomal compartment, a key step in successful transfection. Notably, when cells were subjected to osmotic shock using hypotonic solutions, endosomal permeabilization increased substantially, yielding up to a ten-fold improvement in TE. This approach suggests that manipulation of extracellular conditions represents a promising strategy to overcome the vector’s inherent limitations. In conclusion, our data support the hypothesis that combining low MW (LMW) PDMAEMA with controlled osmotic conditions offers an effective and less cytotoxic alternative to conventional vectors. Future research should further explore PDMAEMA-DNA interactions; assess complex stability, and optimize both polymer formulations and endosomal escape mechanisms to maximize TE
Nanosized Drug Delivery Systems: Colloids and Gels for Site Specific Targeting
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
Graphene quantum dots: From efficient preparation to safe renal excretion
No full text7 figures.-- Supplementary material available on line (6 figures).-- This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation.J. M. G.-D. acknowledges Spanish Ministry of Science, Innovation and Universities for his Juan de la Cierva Incorporación research contract (No. IJCI-2016-27789). This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No. 734834 (INFUSION) and No. 734381 (CARBO-IMmap), and from MIUR. ICN2 is supported by the Severo Ochoa program from Spanish MINECO (No. SEV-2017-0706).Funding note : Open Access funding provided by Università degli Studi di Trieste within the CRUICARE Agreement.Peer reviewe
Geostatistical modelling of health inequalities associated with exposure to road-transport emissions
No full textRoad-transport accounts for a substantial proportion of the air quality objective pollutants experienced within the post-industrial cityscape. Traditionally, investigations have quantified the temporal health effects of such pollutants, yet the confined nature of European intraurban
environments often determine spatial variations in traffic pollutant levels, which tend to be associated with a plethora of social disparities. Recently, elements of spatial heterogeneity have attracted the attention of governmental advisory committees, whom acknowledge a
limited understanding of spatially inclusive practices in-spite of their potentially valuable applications (COMEAP 2006). Through considering spatial variations in children’s respiratory health, across the model British multicultural City of Leicester (Vidal-Hall 2003), this project
aimed to address the inadequacies of temporal models in capturing Pearce et al’s (2010) wider ‘triple jeopardy’.
The projects findings indicated significant global relationships to exist between children’s hospitalisations, social-economic-status, ethnic minorities, and PM10 road-transport emissions within Leicester. ‘Local Indicators of Spatial Association’ and ‘Geographically Weighted Regression’ identified important localised variations within the dataset, specifically relating to a ‘double-burden’ of residentially experienced road-transport emissions and deprivation effecting inner-city children’s respiratory health. Further examination of the spatial
field’s, revealed critical distance-responses to exist between respiratory health fronts and select socio-environmental phenomenon, thus recognising the importance of exposure gradients found in the every-day environment.
It was suggested that exposure to detrimental socio-environmental factors initiated upper respiratory episodes, with prolonged contact impeding recovery leaving the child
vulnerable to infection, exacerbating previous complaints and potentially causing conditions of greater severity. These findings provide a preliminary link between extreme cases of ‘Catarrhal Child Syndrome’ and socio-environmental influences, a conclusion previously eluding medical
practitioners. Interestingly, affluent intra-urban communities tended to contribute the highest levels of emission from private transport, whilst residentially experiencing few environmental burdens. Thus, indicating that environmental injustices prevail across the model British multicultural city of Leicester. To readdress such environmental imbalances, the project suggested and explored a selection of general and community tailored transport schemes. In conclusion, geostatistical approaches are viewed to be an effective set of tools for health and
urban planners, in the management of localised issues, which have previously been ‘filtered’ out by temporal practices
A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial
No full textMulti-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services
