A hydrogel system based on a lactose-modified chitosan for viscosupplementation in osteoarthritis

Osteoarthritis (OA) is a chronic disease affecting joint functionality and often managed with hyaluronic acid (HA) administration. In this study, a hydrogel based on a lactose-modified chitosan (CTL) reticulated with boric acid has been developed as a viscosupplement for OA treatment. The rheological characterization allowed to identify a composition whose properties were in line with those of commercial products (in the order of tens of Pascal). The selected CTL-hydrogel showed biocompatibility and antioxidant activity in vitro, and it did not influence cytokines release by macrophages. Degradation studies carried out over 24 h pointed out its higher resistance to chemical degradation with respect to HA samples. Overall, this study underlines the advantages of the CTL-hydrogel to address the treatment of OA and shed light on an innovative application of CTL polymer, which is one of the main component of the proposed hydrogel system and not used in mixture with other molecules

Stochastic changes affect Solanum wild species following autopolyploidization

Polyploidy is very common within angiosperms, and several studies are in progress to ascertain the effects of early polyploidization at the molecular, physiological, and phenotypic level. Extensive studies are available only in synthetic allopolyploids. By contrast, less is known about the consequences of autopolyploidization. The current study aimed to assess the occurrence and extent of genetic, epigenetic, and anatomical changes occurring after oryzaline-induced polyploidization of Solanum commersonii Dunal and Solanum bulbocastanum Dunal, two diploid (2n=2×=24) potato species widely used in breeding programmes. Microsatellite analysis showed no polymorphisms between synthetic tetraploids and diploid progenitors. By contrast, analysis of DNA methylation levels indicated that subtle alterations at CG and CHG sites were present in tetraploids of both species. However, no change occurred concurrently in all tetraploids analysed with respect to their diploid parent, revealing a stochastic trend in the changes observed. The morpho-anatomical consequences of polyploidization were studied in leaf main veins and stomata. With only a few exceptions, analyses showed no clear superiority of tetraploids in terms of leaf thickness and area, vessel number, lumen size and vessel wall thickness, stomata pore length and width, guard cell width, and stomatal density com- pared with their diploid progenitors. These results are consistent with the hypothesis that there are no traits system- atically associated with autopolyploidy

Weight Loss in Advanced Chronic Kidney Disease: Should We Consider Individualised, Qualitative, ad Libitum Diets? A Narrative Review and Case Study.

In advanced chronic kidney disease, obesity may bring a survival advantage, but many transplant centres demand weight loss before wait-listing for kidney graft. The case here described regards a 71-year-old man, with obesity-related glomerulopathy; referral data were: weight 110 kg, Body Mass Index (BMI) 37 kg/m2, serum creatinine (sCr) 5 mg/dL, estimated glomerular filtration rate (eGFR) 23 mL/min, blood urea nitrogen (BUN) 75 mg/dL, proteinuria 2.3 g/day. A moderately restricted, low-protein diet allowed reduction in BUN (45–55 mg/dL) and good metabolic and kidney function stability, with a weight increase of 6 kg. Therefore, he asked to be enrolled in a weight-loss program to be wait-listed (the two nearest transplant centres required a BMI below 30 or 35 kg/m2). Since previous low-calorie diets were not successful and he was against a surgical approach, we chose a qualitative, ad libitum coach-assisted diet, freely available in our unit. In the first phase, the diet is dissociated; he lost 16 kg in 2 months, without need for dialysis. In the second maintenance phase, in which foods are progressively combined, he lost 4 kg in 5 months, allowing wait-listing. Dialysis started one year later, and was followed by weight gain of about 5 kg. He resumed the maintenance diet, and his current body weight, 35 months after the start of the diet, is 94 kg, with a BMI of 31.7 kg/m2, without clinical or biochemical signs of malnutrition. This case suggests that our patients can benefit from the same options available to non-CKD (chronic kidney disease) individuals, provided that strict multidisciplinary surveillance is assured

Nanocarriers for topical delivery of resveratrol.

Purpose: The aim of the present work was to develop a nanocarrier-based formulation for topical delivery of resveratrol. Methods: Trans-resveratrol (t-res) was encapsulated in liposomes, ethosomes or transferosomes, by a modified hand-shaking method followed by extrusion. All the formulations were characterised in terms of mean diameter, size distribution (I.P.), t-res loading, t-res stability upon encapsulation during storage. The nanocarriers containing t-res were then introduced in cellulose-based gel to allow their final administration on the skin and the viscoelastic properties of the resulting formulation were investigated. Finally, we studied the inhibition of reactive oxygen species (ROS) in human keratinocyte (HaCaT) cell line stimulated with H2O2 for 24 h and then incubated with the t-res containing nanocarriers. Results: All the t-res containing carriers were characterised by a very high (close to 100%) encapsulation efficiency, a negligible t-res release at 4°C and stability of resveratrol in its trans form. The carriers only slightly influenced the viscoelastic characteristics of cellulose-based gels. Nanocarriers encapsulating t-res reduced, in a concentration-dependent manner, ROS production induced by H2O2 and this effect was higher when using t-res-encapsulating nanocarrier, with the higher effect observed in the case of ethosomes. Conclusions: In this work nanocarriers with high encapsulation efficiency, high physical stability and negligible t-res release during storage at 4°C were prepared. To allow their final administration on the skin, the nanocarrier can be easilisy loaded in cellulose-based gels without altering its rheological properties. Moreover, the use of t-res-encapsulating ethosomes led to an efficient antioxidant activity. Further ex vivo and in vivo studies will clarify the role of the different carrier when administered on the skin

Value within otolaryngology: Assessment of the cost-utility analysis literature

AbstractObjectiveTo assess the characteristics and quality of cost utility analyses (CUA) related to otolaryngology within the CEA registry and to summarize their collective results.MethodsAll cost-utility analyses published between 1976 and 2011 contained in the Cost-Effectiveness Analysis Registry (CEA Registry) were evaluated. Topics that fall within the care of an otolaryngologist were included in the review regardless of the presence of an otolaryngologist author. Potential associations between various study characteristics and CEA registry quality scores were evaluated using the Pearson product moment correlation coefficient.ResultsSixty-one of 2913 (2.1%) total CUA publications screened were related to otolaryngology. Eighteen of 61 (29.5%) publications included an otolaryngologist as an author. Fourteen studies agreed on the cost effectiveness of at least unilateral cochlear implantation and six of seven (85.7%) studies demonstrated the cost effectiveness of continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). Forty-six percent (28 of 61) of all manuscripts were published between 2008 and 2011. A more recent publication year was associated with a higher CEA registry quality score while the presence of an otolaryngologist author and journal impact factor had no significant correlation with the quality of the CUA.ConclusionBased on current evidence in the CEA registry, unilateral cochlear implantation for hearing loss and CPAP for OSA are both cost-effective therapeutic interventions. Although CUAs in otolaryngology have increased in quantity and improved in quality in more recent years, there is a relative lack of CUAs in otolaryngology in comparison to other subspecialties

Robust Classification via Support Vector Machines

Classification models are very sensitive to data uncertainty, and finding robust classifiers that are less sensitive to data uncertainty has raised great interest in the machine learning literature. This paper aims to construct robust Support Vector Machine (SVM) classifiers under feature data uncertainty via two probabilistic arguments. The first classifier, Single Perturbation (SP-SVM), reduces the local effect of data uncertainty with respect to one given feature and acts as a local test that could confirm or refute the presence of significant data uncertainty for that particular feature. The second classifier, Extreme Empirical Loss (EEL-SVM), aims to reduce the aggregate effect of data uncertainty with respect to all features, which is possible via a trade-off between the number of prediction model violations and the size of these violations. Both methodologies are computationally efficient and our extensive numerical investigation highlights the advantages and possible limitations of the two robust classifiers on synthetic and real-life data

MicroRNA 199b-5p delivery through stable nucleic acid lipid particles (SNALPs) in tumorigenic cell lines

MicroRNA (miR)-199b-5p has been shown to regulate Hes-1, a downstream effector of the canonical Notch and noncanonical SHH pathways, whereby it impairs medulloblastoma (MB) cancer stem cells (CSCs) through a decrease in the CD133+/CD15+ cell population. Here, we have developed stable nucleic acid lipid particles (SNALPs) that encapsulate miR-199b-5p. The efficacy of the miR- 199b-5p delivery by these SNALPs is demonstrated by significant impairment of Hes-1 levels and CSC markers in a range of different tumorigenic cell lines: colon (HT- 29, CaCo-2, and SW480), breast (MDA-MB231T and MCF-7), prostate (PC-3), glioblastoma (U-87), and MB(Daoy, ONS-76, and UW-228). After treatment with SNALP miR-199b-5p, there is also impairment of cell pro- liferation and no signs of apoptosis, as measured by cas- pases 3/7 activity and annexin V fluorescence cell sorter analyses. These data strengthen the importance of such carriers for miRNA delivery, which show no cytotoxic effects and provide optimal uptake into cells. Thus, efficient target downregulation in different tumorigenic cell lines will be the basis for future preclinical studies

Enhanced antioxidant effect of trans-resveratrol: potential of binary systems with polyethylene glycol and cyclodextrin.

Abstract Trans-resveratrol, a polyphenol extracted from Vitis vinifera, has different beneficial effects following its administration on the skin. Here the potential use of binary systems to enhance in vitro and in vivo activity of trans-resveratrol was investigated. Thus the aqueous solubility of trans-resveratrol was investigated in the presence of growing concentrations of polyethylene glycol (PEG) or β-cyclodextrin (βCD) as solubilizing excipients. Then, the solid dispersion of trans-resveratrol with PEG or inclusion complexes trans-resveratrol/βCD were prepared and characterised by different methods. Cytotoxicity and inhibition of reactive oxygen species (ROS) following H2O2 challenge in the presence of trans-resveratrol, alone or associated to the excipients, was evaluated on human keratinocyte HaCaT cell line. Both the trans-resveratrol-containing binary systems induced significant reduction of H2O2-induced ROS production, especially in the case of βCD that was selected for the following phase of the study. Thus, the effect of a cream containing trans-resveratrol, alone or associated to βCD, on different skin parameters such as corneometry, colorimetry and elastometry, was evaluated on human volunteers. All patients showed a visible improvement of clinical conditions with a remarkable decrease of aging signs, but this effect was higher of the hemi face treated with the βCD-containing formulation versus formulation containing trans-resveratrol alone

Expression and purification of the recombinant subunits of toluene/o-xylene monooxygenase and reconstitution of the active complex.

This paper describes the cloning of the genes coding for each component of the complex of toluene/o-xylene monooxygenase from Pseudomonas stutzeri OX1, their expression, purification and characterization. Moreover, the reconstitution of the active complex from the recombinant subunits has been obtained, and the functional role of each component in the electron transfer from the electron donor to molecular oxygen has been determined. The coexpression of subunits B, E and A leads to the formation of a subcomplex, named H, with a quaternary structure (BEA)2, endowed with hydroxylase activity. Tomo F component is an NADH oxidoreductase. The purified enzyme contains about 1 mol of FAD, 2 mol of iron, and 2 mol of acid labile sulfide per mol of protein, as expected for the presence of one [2Fe-2S] cluster, and exhibits a typical flavodoxin absorption spectrum. Interestingly, the sequence of the protein does not correspond to that previously predicted on the basis of DNA sequence. We have shown that this depends on minor errors in the gene sequence that we have corrected. C component is a Rieske-type ferredoxin, whose iron and acid labile sulfide content is in agreement with the presence of one [2Fe-2S] cluster. The cluster is very sensitive to oxygen damage. Mixtures of the subcomplex H and of the subunits F, C and D are able to oxidize p-cresol into 4-methylcathecol, thus demonstrating the full functionality of the recombinant subunits as purified. Finally, experimental evidence is reported which strongly support a model for the electron transfer. Subunit F is the first member of an electron transport chain which transfers electrons from NADH to C, which tunnels them to H subcomplex, and eventually to molecular oxyge