Phenolic-rich extracts from acerola, cashew apple and mango by-products cause diverse inhibitory effects and cell damages on enterotoxigenic Escherichia coli.

This study aimed to evaluate the inhibitory effects of phenolic-rich extracts from acerola (Malpighia emarginata D.C., PEA), cashew apple (Anacardium occidentale L., PEC) and mango (Mangifera indica L., PEM) by-products on distinct enterotoxigenic Escherichia coli (ETEC) strains. The capability of PEA and PEC of impairing various physiological functions of ETEC strains was investigated with multiparametric flow cytometry. Procyanidin B2 , myricetin and p-coumaric acid were the major phenolic compounds in PEA, PEC and PEM, respectively. PEA and PEC had lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) (MIC: 31·25 mg ml-1 ; MBC: 62·5 mg ml-1 ) on ETEC strains than PEM (MIC and MIC: >1000 mg ml-1 ). PEA and PEC (15·6, 31·2, 62·5 mg ml-1 ) caused viable count reductions (P < 0·05) on ETEC strains after 24 h of exposure, notably the ≥3 log reductions caused by 62·5 mg ml-1 . The 24 h exposure of ETEC strains to PEA and PEC (31·2, 62·5 mg ml-1 ) led to high sizes of cell subpopulations with concomitant impairments in cell membrane polarization and permeability, as well as in enzymatic, respiratory and efflux activities. PEA and PEC are effective in inhibiting ETEC through a multi-target action mode with disturbance in different physiological functions.

One year of surgical mask testing at the University of Bologna labs: Lessons learned from data analysis.

The outbreak of SARS-CoV-2 pandemic highlighted the worldwide lack of surgical masks and personal protective equipment, which represent the main defense available against respiratory diseases as COVID-19. At the time, masks shortage was dramatic in Italy, the first European country seriously hit by the pandemic: aiming to address the emergency and to support the Italian industrial reconversion to the production of surgical masks, a multidisciplinary team of the University of Bologna organized a laboratory to test surgical masks according to European regulations. The group, driven by the expertise of chemical engineers, microbiologists, and occupational physicians, set-up the test lines to perform all the functional tests required. The laboratory started its activity on late March 2020, and as of the end of December of the same year 435 surgical mask prototypes were tested, with only 42 masks compliant to the European standard. From the analysis of the materials used, as well as of the production methods, it was found that a compliant surgical mask is most likely composed of three layers, a central meltblown filtration layer and two external spunbond comfort layers. An increase in the material thickness (grammage), or in the number of layers, does not improve the filtration efficiency, but leads to poor breathability, indicating that filtration depends not only on pure size exclusion, but other mechanisms are taking place (driven by electrostatic charge). The study critically reviewed the European standard procedures, identifying the weak aspects; among the others, the control of aerosol droplet size during the bacterial filtration test results to be crucial, since it can change the classification of a mask when its performance lies near to the limiting values of 95 or 98%.

Mediated Interactions and Photon Bound States in an Exciton-Polariton Mixture.

The quest to realize strongly interacting photons remains an outstanding challenge both for fundamental science and for applications. Here, we explore mediated photon-photon interactions in a highly imbalanced two-component mixture of exciton polaritons in a semiconductor microcavity. Using a theory that takes into account nonperturbative correlations between the excitons as well as strong light-matter coupling, we demonstrate the high tunability of an effective interaction between quasiparticles formed by minority component polaritons interacting with a Bose-Einstein condensate (BEC) of a majority component polaritons. In particular, the interaction, which is mediated by sound modes in the BEC can be made strong enough to support a bound state of two quasiparticles. Since these quasiparticles consist partly of photons, this in turn corresponds to a dimer state of photons propagating through the BEC. This gives rise to a new light transmission line where the dimer wave function is directly mapped onto correlations between the photons. Our findings open new routes for highly nonlinear optical materials and novel hybrid light-matter quantum systems.

Probiotic properties of yeasts isolated from Brazilian fermented table olives.

AIMS: To investigate the probiotic potential of yeasts isolated from naturally fermented Brazilian table olives. METHODS AND RESULTS: Eighteen yeast strains were tested in terms of: safety; survival of gastrointestinal and digestion conditions; antimicrobial activity; cellular hydrophobicity; autoaggregation ability and adhesion to epithelial cells; coaggregation and inhibition of pathogenic bacteria adhesion. Six yeasts showed favourable results for all probiotic attributes: Saccharomyces cerevisiae CCMA 1746, Pichia guilliermondii CCMA 1753, Candida orthopsilosis CCMA 1748, Candida tropicalis CCMA 1751, Meyerozyma caribbica CCMA 1758 and Debaryomyces hansenii CCMA 1761. These yeasts demonstrated resistance to 37°C, pH 2·0 and bile salts, and survived in vitro digestion (≥106  CFU per ml). Furthermore, the yeasts exhibited a hydrophobic cell surface (42·5-92·2%), autoaggregation capacity (41·0-91·0%) and adhesion to Caco-2 (62·0-82·8%) and HT-29 (57·6-87·3%) epithelial cell lines. Also, the strains showed antimicrobial activity against Salmonella Enteritidis as well as the ability to coaggregate and reduce the adhesion of this pathogen to intestinal cells. CONCLUSIONS: Autochthonous yeasts from naturally fermented Brazilian table olives have probiotic properties, with potential for development of new probiotic food products. SIGNIFICANCE AND IMPACT OF STUDY: These data are important and contribute to the knowledge of new potential probiotic yeasts capable of surviving gastrointestinal tract conditions and inhibiting pathogenic bacteria.

Acerola (Malpighia glabra L.) and guava (Psidium guayaba L.) industrial processing by-products stimulate probiotic Lactobacillus and Bifidobacterium growth and induce beneficial changes in colonic microbiota.

AIMS: This study evaluated whether by-products from industrial processing of acerola (Malpighia glabra L.; AB) and guava (Psidium guajava L.; GB) fruit may stimulate the growth and metabolism of probiotic Lactobacillus and Bifidobacterium and induce changes in human colonic microbiota. METHODS AND RESULTS: The ability of non-digested and digested AB or GB to stimulate the growth ad metabolism of Lactobacillus acidophilus LA-05, Lactobacillus casei L-26 and Bifidobacterium animalis subsp. lactis BB-12 was evaluated. Changes in populations of distinct bacterial groups of human colonic microbiota induced by digested AB and GB were evaluated using an in vitro colonic fermentation system. Non-digested and digested AB and GB favoured probiotic growth. No difference among counts of probiotics in media with glucose, fructooligosaccharides and non-digested and digested AB and GB was found during a 48-h cultivation. Cultivation of probiotics in media with non-digested and digested AB and GB resulted in decreased pH, increased organic acid production and sugar consumption over time. Digested AB and GB caused overall beneficial changes in abundance of Bifidobacterium spp., Lactobacillus-Enterococcus, Eubacterium rectall-Clostridium coccoides and Bacteroides-Provotella populations, besides to decrease the pH and increase the short-chain fatty acid production during a 24-h in vitro colonic fermentation. CONCLUSION: AB and GB could be novel prebiotic ingredients because they can stimulate the growth and metabolism of probiotics and induce overall beneficial changes in human colonic microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: AB and GB stimulated the growth and metabolism of probiotics, in addition to induce beneficial alterations in human colonic microbiota composition and increase short-chain fatty acid production. These results characterize AB and GB as potential prebiotic ingredients and fruit processing by-products as sources of added-value compounds.

Efficacy of oregano and rosemary essential oils to affect morphology and membrane functions of noncultivable sessile cells of Salmonella Enteritidis 86 in biofilms formed on stainless steel.

AIMS: This study evaluated the efficacy of essential oil from Origanum vulgare L. (oregano; OVEO) and Rosmarinus officinalis L. (rosemary; ROEO) to inactivate sessile cells of Salmonella enterica serovar Enteritidis 86 (SE86) in young and mature biofilms formed on stainless steel. METHODS AND RESULTS: Ultrastructural alterations and damage in different physiological functions caused by OVEO and ROEO in noncultivable sessile cells of SE86 were investigated using scanning electron microscopy and flow cytometry. OVEO (2·5 µl ml-1 ) and ROEO (40 µl ml-1 ) were effective to eradicate young and mature biofilms formed by SE86 sessile cells on stainless steel surfaces; however, the efficacy varied with exposure time. OVEO and ROEO caused alterations in morphology of SE86 sessile cells, inducing the occurrence of bubbles or spots on cell surface. OVEO and ROEO compromised membrane polarization, permeability and efflux activity in noncultivable SE86 sessile cells. These findings show that OVEO and ROEO act by a multitarget mechanism on SE86 membrane functions. CONCLUSIONS: ROEO and OVEO showed efficacy to eradicate SE86 sessile cells in preformed biofilms on stainless steel, displaying a time-dependent effect and multitarget action mode on bacterial cell membrane. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides for the first time the effects of OVEO and ROEO on morphology and physiological functions of noncultivable sessile cells of S. Enteritidis biofilms preformed on stainless steel surfaces.

MTHFR, TS and XRCC1 genetic variants may affect survival in patients with myelodysplastic syndromes treated with supportive care or azacitidine.

We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0.001; P=0.026; P=0.058; P=0.024). MTHFR 677T/T, TS 3'-UTR -6 bp/-6 bp and XRCC1 399G/G genotypes were associated with short survival in patients receiving azacitidine by multivariate analysis (P<0.001; P=0.004; P=0.002). We then performed an exploratory analysis to evaluate the effect of the simultaneous presence of multiple adverse variant genotypes. Interestingly, patients with ⩾1 adverse genetic variants had a short survival, independently from their International Prognostic Scoring System (IPSS) and therapy received. To our knowledge, this is the first study showing that polymorphisms in folate-metabolizing pathway, DNA synthesis and DNA repair genes could influence survival of MDS patients.

Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity. METHODS: The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False Discovery Rate (FDR) procedure was used. RESULTS: FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia. CONCLUSIONS: This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.

Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer.

Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (HK-1) and 2 (HK-2), embryonic pyruvate kinase (PKM-2), lactate dehydrogenase-A (LDH-A), glucose transporter-1 (GLUT-1), voltage-dependent anion-selective channel protein-1 (VDAC-1). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied. GLUT-1, LDH-A, HK-1, PKM-2 and VDAC-1 mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for LDH-A expression only. RAS mutation-positive disease was associated with high GLUT-1 mRNA expression levels only. Right-sided colon tumors showed significantly higher GLUT-1, PKM-2 and LDH-A mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic, RAS-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics.

Clinical impact of the HGF/MET pathway activation in patients with advanced gastric cancer treated with palliative chemotherapy.

In gastric cancer, available clinical studies focusing on the activated hepatocyte growth factor (HGF)/MET pathway are limited to surgical and often heterogeneous series. MET copy number gain (CNG) and an activating truncation in the HGF promoter (deoxyadenosine tract element, DATE+) were studied in tumors of 95 patients with advanced gastric cancer treated with palliative chemotherapy. Associations with overall survival (OS) and the pattern of metastatic disease were studied. Median OS was 9.7 months in 80 MET CNG <5 copies cases (MET-), and 6.4 months in 15 MET CNG was ⩾5 copies cases (MET+) (P=0.001). MET+ status confirmed the adverse prognostic effect in the multivariate model. A significantly different distribution of MET+/DATE+ and MET-/DATE- cases was observed between patients with and without peritoneal carcinomatosis (PC). MET+ status confirms its adverse prognostic role in advanced gastric cancer patients. The activated MET/HGF axis seems to be associated with PC. These findings are relevant to the development of anti-MET/HGF compounds.

Quantum multifractality as a probe of phase space in the Dicke model.

We study the multifractal behavior of coherent states projected in the energy eigenbasis of the spin-boson Dicke Hamiltonian, a paradigmatic model describing the collective interaction between a single bosonic mode and a set of two-level systems. By examining the linear approximation and parabolic correction to the mass exponents, we find ergodic and multifractal coherent states and show that they reflect details of the structure of the classical phase space, including chaos, regularity, and features of localization. The analysis of multifractality stands as a sensitive tool to detect changes and structures in phase space, complementary to classical tools to investigate it. We also address the difficulties involved in the multifractal analyses of systems with unbounded Hilbert spaces.

Genomic DNA in human blastocoele fluid.

IVF often requires embryo cryopreservation through vitrification. During the vitrification process, the embryos can be collapsed by withdrawing the blastocoele fluid. The metabolomic profile of blastocoele fluid has been recently investigated by high-performance liquid chromatography-electrospray ionization-mass spectrometry to provide metabolite information that can help estimations of implantation efficiency. However, the presence of embryo DNA in blastocoele fluid has not been reported to date. This study shows using real-time PCR that genomic DNA was present in about 90% of blastocoele fluid samples harvested during the vitrification procedure. Moreover, the potential for determining embryo sex directly from blastocoele fluid is demonstrated by amplifying the multicopy genes TSPY1 (on the Y chromosome) and TBC1D3 (on chromosome 17). This opens up the possibility of screening embryos from couples carrying an X-linked disorder to identify male embryos at high risk of disease. The application of whole-genome amplification technologies to fluid samples is also shown to be feasible, potentially allowing more comprehensive genetic tests. As proof of principle, microarray comparative genomic hybridization was attempted to confirm the sex of embryos as well as detect several aneuploidies. However, further studies are needed to validate this approach and confirm that the accuracy is sufficient for diagnostic purposes.

Recent advances in synthesis, characterization of hydroxyapatite/polyurethane composites and study of their biocompatible properties.

The development of engineered biomaterials that mimic bone tissues is a promising research area that benefits from a growing interest. Polymers and polymer-ceramic composites are the principle materials investigated for the development of synthetic bone scaffolds thanks to their proven biocompatibility and biostability. Several polymers have been combined with calcium phosphates (mainly hydroxyapatite) to prepare nanocomposites with improved biocompatible and mechanical properties. Here, we report the hydrothermal synthesis in high pressure conditions of nanostructured composites based on hydroxyapatite and polyurethane functionalized with carboxyl and thiol groups. Cell-material interactions were investigated for potential applications of these new types of composites as coating for orthopedic implants. Physical-chemical and morphological characteristics of hydroxyapatite/polyurethane composites were evaluated for different compositions, showing their dependence on synthesis parameters (pressure, temperature). In vitro experiments, performed to verify if these composites are biocompatible cell culture substrates, showed that they are not toxic and do not affect cell viability.

Nutritional and sensory characteristics of Minas fresh cheese made with goat milk, cow milk, or a mixture of both.

This study aimed to assess and compare the nutritional, technological, and sensory characteristics of Minas fresh cheese made with goat milk, cow milk, or a mixture of the two stored in cold conditions for 21d. The yield and centesimal composition of the cheeses were not affected by the type of milk used in their preparation. Reductions were observed in the moisture content, pH, proteolysis index, and instrumental hardness; moreover, increases were observed in the syneresis, acidity index, and depth of proteolysis index in all cheeses. The percentages of caprylic, capric, oleic, and linoleic fatty acids were higher in goat milk cheese and cheese made with a mixture of goat and cow milk compared with cow milk cheese, and a sensory evaluation revealed differences in color, flavor, and aroma between the cheeses. The preparation of Minas fresh cheese with a mixture of goat and cow milk can be a viable alternative for dairy products in the market that can be characterized as high-quality products that meet consumer demands.

Micro-ornamentation patterns in different areas of the epidermis in the gecko Tarentola mauritanica reflect variations in the accumulation of corneous material in Oberhautchen cells.

Micro-ornamentations characterize the surface of scales in lepidosaurians and are summarized in four main patterns, i.e., spinulated, lamellated, lamellate-dentate, and honeycomb, although variations of these patterns are present in different species. Although geckos are known to possess a spinulated pattern derived from the Oberhautchen layer, also other pattern variations of the spinulated micro-ornamentation are present such as those indicated as dendritic ramification, corneous belts, and small bare patches. The present study mainly describes the variation of micro-ornamentations present in scales of different skin regions in the Mediterranean gecko Tarentula mauritanica using scannig and transmission electron microscopy. The study reports that the accumulation of corneous material in Oberhautchen cells is not homogenous in different areas of body scales and, when mature, this process gives rise to different sculpturing on the epidermal surface generating not only spinulae but also transitional zones leading to the other main patterns. It is hypothesized that spinulae formation derives from the vertical and lateral symmetric growth of tubercolate, non-overlapped scales of geckos. Sparse areas also result smooth or with serpentine-ridges likely revealing the beta-layer located underneath and merged with the Oberhautchen. The eco-functional role of this variable micro-ornamentation in the skin of lizards however remains largely speculative.

Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms.

The aim of this study is to investigate the role of single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) and of the related co-chaperone FKBP5 genes in the development of glucocorticoid (GC) resistance in Crohn's disease (CD) and ulcerative colitis (UC) patients. We have developed a high-resolution DNA melting method that allows simultaneous identification of GR (BclI, N363S and ER22/23EK) and FKBP5 (rs3800373, rs1360780 and rs4713916) polymorphisms. Genotype frequencies were determined in 100 consecutive CD and 100 UC patients under GCs therapy (50 responders and 50 resisters). The variation of FKBP5 polymorphism rs4713916 (G/A), in the putative promoter region of FKBP5, is significantly associated with resistance to GC treatment in CD (responder=17% versus resister=35%; P=0.0043). No significant differences were found in UC patients. If these preliminary findings will be confirmed, the combination of GR and FKBP5 mutational analyses could help to identify subgroups of CD patients with higher chances to benefit from GC treatment.

Quantum localization measures in phase space.

Measuring the degree of localization of quantum states in phase space is essential for the description of the dynamics and equilibration of quantum systems, but this topic is far from being understood. There is no unique way to measure localization, and individual measures can reflect different aspects of the same quantum state. Here we present a general scheme to define localization in measure spaces, which is based on what we call Rényi occupations, from which any measure of localization can be derived. We apply this scheme to the four-dimensional unbounded phase space of the interacting spin-boson Dicke model. In particular, we make a detailed comparison of two localization measures based on the Husimi function in the regime where the model is chaotic, namely, one that projects the Husimi function over the finite phase space of the spin and another that uses the Husimi function defined over classical energy shells. We elucidate the origin of their differences, showing that in unbounded spaces the definition of maximal delocalization requires a bounded reference subspace, with different selections leading to contextual answers.

Genetic modulation of the Let-7 microRNA binding to KRAS 3'-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan.

There is increasing evidence that the Let-7 microRNA (miRNA) exerts an effect as a tumor suppressor by targeting the KRAS mRNA. The Let-7 complementary site (LCS6) T>G variant in the KRAS 3'-untranslated region weakens Let-7 binding. We analyzed whether the LCS6 variant may be clinically relevant to patients with metastatic colorectal cancer (MCRC) treated with anti-epidermal growth factor receptor (EGFR) therapy. LCS6 genotypes and KRAS/BRAF mutations were determined in the tumor DNA of 134 patients with MCRC who underwent salvage cetuximab-irinotecan therapy. There were 34 G-allele (T/G+G/G) carriers (25%) and 100 T/T genotype carriers (75%). G-allele carriers were significantly more frequent in the KRAS mutation group than in patients with KRAS wild type (P=0.004). In the 121 patients without BRAF V600E mutation, overall survival (OS) and progression-free survival (PFS) times were compared between carriers of the LCS6 G-allele genotypes and carriers of the wild-type T/T genotype. LCS6 G-allele carriers showed worse OS (P=0.001) and PFS (P=0.004) than T/T genotype carriers (confirmed in the multivariate model including the KRAS status). In the exploratory analysis of the 55 unresponsive patients with KRAS mutation, LCS6 G-allele carriers showed adverse OS and PFS times. These findings deserve additional investigations as they may open novel perspectives for the treatment of patients with MCRC.

Ultrasound-detected synovitis with power Doppler signal is associated with severe radiographic damage and reduced cartilage thickness in hand osteoarthritis.

OBJECTIVES: To examine ultrasound (US) features of synovitis in hand osteoarthritis (OA) joints, and to evaluate their relationship with radiological damage severity and US-detected cartilage thickness. METHODS: US examination was carried out on 14 joints of both hands of 25 patients with symptomatic hand OA (HOA) and 10 age- and sex-matched control subjects. US-detected features were: synovial hypertrophy, effusion, power Doppler signal (PDS), cartilage thickness. Conventional hand radiographs were scored utilizing the Kellgren-Lawrence and Kallman systems. HOA patients were divided into two subsets: non-erosive and erosive. RESULTS: Among the three groups of subjects studied, erosive OA showed the highest values of radiological scores and the highest prevalence of US-detected synovitis. Joints positive for US synovitis features (above all PDS) had higher radiological scores and lower cartilage thickness, while joints with X-ray detected central erosions [the hallmark of erosive HOA were more likely to present PDS positivity. US measured cartilage thickness inversely correlated with radiological damage scores. CONCLUSIONS: US-detected synovitis is present in about 10% of HOA finger joints and is associated with more severe radiological damage and reduced cartilage thickness. PDS and cartilage thickness (mm) may represent two innovative additional information tools provided by ultrasonography in HOA evaluation.

Improved cellular uptake of functionalized single-walled carbon nanotubes.

Single-walled carbon nanotubes (SWNTs) due to their unique structural and physicochemical properties, have been proposed as delivery systems for a variety of diagnostic and therapeutic agents. However, SWNTs have proven difficult to solubilize in aqueous solution, limiting their use in biological applications. In an attempt to improve SWNTs' solubility, biocompatibility, and to increase cell penetration we have thoroughly investigated the construction of carbon scaffolds coated with aliphatic carbon chains and phospholipids to obtain micelle-like structures. At first, oxidized SWNTs (2370 ± 30 nmol mg(-1) of SWNTs) were covalently coupled with an alcoholic chain (stearyl alcohol, C(18)H(37)OH; 816 nmol mg(-1) of SWNTs). Subsequently, SWNTs-COOC(18)H(37) derivatives were coated with phosphatidylethanolamine (PE) or -serine (PS) phospholipids obtaining micelle-like structures. We found that cellular uptake of these constructs by phagocytic cells occurs via an endocytotic mechanism for constructs larger than 400 nm while occurs via diffusion through the cell membrane for constructs up to 400 nm. The material that enters the cell by phagocytosis is actively internalized by macrophages and localizes inside endocytotic vesicles. In contrast the material that enters the cells by diffusion is found in the cell cytosol. In conclusion, we have realized new biomimetic constructs based on alkylated SWNTs coated with phospholipids that are efficiently internalized by different cell types only if their size is lower than 400 nm. These constructs are not toxic to the cells and could now be explored as delivery systems for non-permeant cargoes.