Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study

Peripheral artery occlusive disease is an emerging cardiovascular disease characterized by the blockage of blood vessels in the limbs and is associated with dysfunction, gangrene, amputation, and a high mortality risk. Possible treatments involve by-pass surgery using autologous vessel grafts, because of the lack of suitable synthetic small-diameter vascular prosthesis. One to five percent of patients experience vascular graft infection, with a high risk of haemorrhage, spreading of the infection, amputation and even death. In this work, an infection-proof vascular graft prototype was designed and manufactured by electrospinning 12.5% w/v poly-L-lactic-co-glycolic acid solution in 75% v/v dichloromethane, 23.8% v/v dimethylformamide and 1.2% v/v water, loaded with 0.2% w/w_PLGA. Polymer and tobramycin concentrations were selected after viscosity and surface tension and after HPLC-UV encapsulation efficiency (EE%) evaluation, respectively. The final drug-loaded prototype had an EE% of 95.58% ± 3.14%, with smooth fibres in the nanometer range and good porosity; graft wall thickness was 291 ± 20.82 μm and its internal diameter was 2.61 ± 0.05 mm. The graft’s antimicrobic activity evaluation through time-kill assays demonstrated a significant and strong antibacterial activity over 5 days against Staphylococcus aureus and Escherichia coli. An indirect cell viability assay on Normal Human Dermal Fibroblasts (NHDF) confirmed the cytocompatibility of the grafts.     

Picosecond GaAs photoconductors on silicon substrates for localintegration with silicon devices and circuits

A fabrication procedure for local integration of GaAs photoconductive devices with processed silicon circuits is discussed. The process allows isolated regions of GaAs to be epitaxially grown by MBE at temperatures which are compatible with already processed silicon circuits with first-level metallization. GaAs photoconductors with 15-μm gap lengths fabricated on silicon substrates have exhibited >16-mA sampling-oscilloscope-limited responses, with electrical pulse widths less than 20 ps as determined by autocorrelation measurements     

Guar gum methyl ethers. Part I. Synthesis and macromolecular characterization

Guar gum (GG) has been partially methyl-etherified under heterogeneous reaction conditions. The resulting products, (methyl ether guar: MG) with different degrees of substitution, have been characterized by means of viscosity, ¹H NMR, and FTIR measurements. The introduction of methoxyl groups along the polysaccharidic chains reduces the hydrogen bonding sites on the guar backbone reducing primarely the extent of hydrogen bonding between guar macromolecules, hence their aggregation tendency. A comparative analysis of Mark–Houwink–Sakurada parameters and of the characteristic ratio (C_∞) of GG and MG samples in aqueous solution has been carried out using the Burchard–Stockmayer–Fixman method for flexible and semiflexible chains. The MG chains exhibit more flexibility than those of native guar gum which is traceable to a disruption of intrachain hydrogen bonds.     

Methylome Profiling in Fabry Disease in Clinical Practice: A Proof of Concept

Anderson–Fabry disease (FD) is an X-linked disease caused by a functional deficit of the α-galactosidase A enzyme. FD diagnosis relies on the clinical manifestations and research of GLA gene mutations. However, because of the lack of a clear genotype/phenotype correlation, FD diagnosis can be challenging. Recently, several studies have highlighted the importance of investigating DNA methylation patterns for confirming the correct diagnosis of different rare Mendelian diseases, but to date, no such studies have been reported for FD. Thus, in the present investigation, we analyzed for the first time the genome-wide methylation profile of a well-characterized cohort of patients with Fabry disease. We profiled the methylation status of about 850,000 CpG sites in 5 FD patients, all carrying the same mutation in the GLA gene (exon 6 c.901C>G) and presenting comparable low levels of α-Gal A activity. We found that, although the whole methylome profile did not discriminate the FD group from the unaffected one, several genes were significantly differentially methylated in Fabry patients. Thus, we provide here a proof of concept, to be tested in patients with different mutations and in a larger cohort, that the methylation state of specific genes can potentially identify Fabry patients and possibly predict organ involvement and disease evolution.     

An anion-permeable polymeric coating for the protection of a semiconductor photoelectrode against decomposition

An anion-permeable polymeric film has been applied to the surfaces of cadmium sulfide photoanodes to decrease the rate of electrode corrosion which is observed during the photoelectro-chemical oxidation of aqueous species. Although the rate of surface corrosion was reduced, film adhesion problems were observed.     

The imaginary,the computer,artificial intelligence: A cultural anthropological approach

The role of the cultural anthropologist in studying the results of information technology and artificial intelligence should be to contribute and reaffirm a sense of life which considers the human being in his or her totality, and to recognize the role of diversity and the imaginary. Technical revolutions have also proved to be cultural revolutions. The skills required by one culture, the identification and creation of problems and the solutions are interrelated. These interrelationships are worked out in a cultural context endowed with its own experiences, knowledge and needs which define and make it different from other societies. The advanced technologies require new competences and new skills. This paper examines imaginary from two different viewpoints: (a) the imaginary aspect of body-mind relations, influenced by research into artificial intelligence and its prospects for the future; and (b) the roles and forms assumed by the imaginary in human-computer relations.     

Detection of Germline Variants in 450 Breast/Ovarian Cancer Families with a Multi-Gene Panel Including Coding and Regulatory Regions

With the progress of sequencing technologies, an ever-increasing number of variants of unknown functional and clinical significance (VUS) have been identified in both coding and non-coding regions of the main Breast Cancer (BC) predisposition genes. The aim of this study is to identify a mutational profile of coding and intron-exon junction regions of 12 moderate penetrance genes (ATM, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53) in a cohort of 450 Italian patients with Hereditary Breast/Ovarian Cancer Syndrome, wild type for germline mutation in BRCA1/2 genes. The analysis was extended to 5′UTR and 3′UTR of all the genes listed above and to the BRCA1 and BRCA2 known regulatory regions in a subset of 120 patients. The screening was performed through NGS target resequencing on the Illumina platform MiSeq. 8.7% of the patients analyzed is carriers of class 5/4 coding variants in the ATM (3.6%), BRIP1 (1.6%), CHEK2 (1.8%), PALB2 (0.7%), RAD51C (0.4%), RAD51D (0.4%), and TP53 (0.2%) genes, while variants of uncertain pathological significance (VUSs)/class 3 were identified in 9.1% of the samples. In intron-exon junctions and in regulatory regions, variants were detected respectively in 5.1% and in 32.5% of the cases analyzed. The average age of disease onset of 44.4 in non-coding variant carriers is absolutely similar to the average age of disease onset in coding variant carriers for each proband’s group with the same cancer type. Furthermore, there is not a statistically significant difference in the proportion of cases with a tumor onset under age of 40 between the two groups, but the presence of multiple non-coding variants in the same patient may affect the aggressiveness of the tumor and it is worth underlining that 25% of patients with an aggressive tumor are carriers of a PTEN 3′UTR-variant. This data provides initial information on how important it might be to extend mutational screening to the regulatory regions in clinical practice.     

Influence of sketch types on distributed design team work

Product development is a collaborative activity more often than ever carried out by distributed design teams. It is critical to determine how sketches are used in such environments in order to improve the design process. Sketches produced by students participating in a collaborative design project of three European Universities are classified according to the intention of the designer when producing a sketch, the level of detail shown in the sketch and the phase when the sketch was produced. The adapted classification system used in this paper helps to analyse type of sketches with most variety of ideas. Furthermore, this paper reviews which type of sketches offers the most potential to be further developed. Results show that persuasive sketches offer the broadest range of ideas since they are produced as a combination of ideas from brainstorming sessions. Shared sketches help to achieve consensus in decision-making since the sketches are most likely to be produced by the entire group rather than individually.     

Effects of high glucose on vascular endothelial growth factor synthesis and secretion in aortic vascular smooth muscle cells from obese and lean zucker rats

Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF), a molecule produced also by Vascular Smooth Muscle Cells (VSMC). We aimed at evaluating the role of high glucose on VEGF-A(164) synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR). In cultured aortic VSMC from LZR and OZR incubated for 24 h with d-glucose (5.5, 15 and 25 mM) or with the osmotic controls l-glucose and mannitol, we measured VEGF-A(164) synthesis (western, blotting) and secretion (western blotting and ELISA). We observed that: (i) d-glucose dose-dependently increases VEGF-A(164) synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002-0.0001); (ii) all the effects of 15 and 25 mM d-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001); (iii) l-glucose and mannitol reproduce the VEGF-A(164) modulation induced by d-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.