Biochar Particles Obtained from Agricultural Carob Waste as a Suitable Filler for Sustainable Biocomposite Formulations.

In the context of sustainable and circular economy, the recovery of biowaste for sustainable biocomposites formulation is a challenging issue. The aim of this work is to give a new life to agricultural carob waste after glucose extraction carried out by a local factory for carob candy production. A pyrolysis process was carried out on bio-waste to produce biofuel and, later, the solid residual fraction of pyrolysis process was used as interesting filler for biocomposites production. In this work, biochar particles (BC) as a pyrolysis product, after fuels recovery of organic biowaste, specifically, pyrolyzed carobs after glucose extraction, were added on poly(butylene-adipate-co-terephthalate), (PBAT), at two different concentrations, i.e., 10 and 20 wt%. The BC have been produced using three pyrolysis processing temperatures (i.e., 280, 340 and 400 °C) to optimize the compositions of produced solid fractions and biofuels. The resulting particles from the pyrolysis process (BC280, BC340 and BC400) were considered as suitable fillers for PBAT. Firstly, the BC particles properties were characterized by elemental composition and spectroscopy analysis, particle size measurements and evaluation of radical scavenging activity and efficiency. Moreover, PBAT/BC composites were subjected to analysis of their rheological and thermal behavior, morphologies and mechanical properties. In addition, accelerated weathering, monitored by both tensile test and spectroscopic analysis, was carried out, and obtained results show that the biochar particles can exert a beneficial effect on photo-oxidation delay of PBAT matrix.

Irisin Serum Levels and Skeletal Muscle Assessment in a Cohort of Charcot-Marie-Tooth Patients.

Background: Charcot-Marie-Tooth (CMT) indicates a group of inherited polyneuropathies whose clinical phenotypes primarily include progressive distal weakness and muscle atrophy. Compelling evidence showed that the exercise-mimetic myokine irisin protects against muscle wasting in an autocrine manner, thus possibly preventing the onset of musculoskeletal atrophy. Therefore, we sought to determine if irisin serum levels correlate with biochemical and muscle parameters in a cohort of CMT patients. Methods: This cohort study included individuals (N=20) diagnosed with CMT disease. Irisin and biochemical markers were quantified in sera. Skeletal muscle mass (SMM) was evaluated by bioelectric impedance analysis, muscle strength by handgrip, and muscle quality was derived from muscle strength and muscle mass ratio. Results: CMT patients (m/f, 12/8) had lower irisin levels than age and sex matched healthy subjects (N=20) (6.51 ± 2.26 vs 9.34 ± 3.23 µg/ml; p=0.003). SMM in CMT patients was always lower compared to SMM reference values reported in healthy Caucasian population matched for age and sex. Almost the totality of CMT patients (19/20) showed low muscle quality and therefore patients were evaluated on the basis of muscle strength. Irisin was lower in presence of pathological compared to normal muscle strength (5.56 ± 1.26 vs 7.67 ± 2.72 µg/ml; p=0.03), and directly correlated with the marker of bone formation P1PN (r= 0.669; 95%CI 0.295 to 0.865; p=0.002), but inversely correlated with Vitamin D (r=-0.526; 95%CI -0,791 to -0,095; p=0.017). Surprisingly, in women, irisin levels were higher than in men (7.31 ± 2.53 vs 5.31 ± 1.02 µg/ml, p=0.05), and correlated with both muscle strength (r=0.759; 95%CI 0.329 to 0.929; p=0.004) and muscle quality (r=0.797; 95%CI 0.337 to 0.950; p=0.006). Conclusion: Our data demonstrate lower irisin levels in CMT patients compared to healthy subjects. Moreover, among patients, we observed, significantly higher irisin levels in women than in men, despite the higher SMM in the latter. Future studies are necessary to establish whether, in this clinical contest, irisin could represent a marker of the loss of muscle mass and strength and/or bone loss.

Optical coherence tomography angiography to assess vascular remodeling of the choriocapillaris after low-fluence photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: To evaluate the efficacy of optical coherence tomography angiography (OCTA) in identifying changes in the choriocapillaris layer after low-fluence verteporfin photodynamic therapy (vPDT) in patients affected by chronic central serous chorioretinopathy (CSCR). METHODS: Low-fluence vPDT was performed on 28 eyes of 27 patients with CSCR. All patients underwent the following tests at baseline and 6 months after treatment: best corrected visual acuity (BCVA), fluorescein angiography, indocyanine green angiography, enhanced depth imaging OCT and OCTA. RESULTS: Subretinal fluid was completely absorbed in 18 of the 28 affected eyes (64.3%) after low-fluence vPDT ("responders"), and incompletely absorbed in 10 eyes (35.7%) ("non responders"). BCVA was significantly improved (p = 0.006) whereas central foveal thickness and choroidal foveal thickness were significantly decreased (p = 0.001 and p = 0.00 respectively) 6 months after treatment in responders. CONCLUSIONS: OCTA revealed a different pattern of vascular remodeling of the choriocapillaris between CSC patients who responded and those who did not respond to low-fluence vPDT.

Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer Aged at Least 75 Years: A Post-Hoc Subgroup Analysis of Three Phase II Trials.

Patients older than 75 years of age are usually excluded from metastatic colorectal cancer studies based on a combination chemotherapy containing oxaliplatin. Our group conducted three phase II trials in elderly patients in recent years. A post-hoc subgroup analysis of 67 patients aged at least 75 years was included in this study. Oxaliplatin was combined with capecitabine in two trials and with uracil-tegafur (UFT) plus folinic acid in the third trial. In one study, bevacizumab was also added to chemotherapy. The median age of patients was 77 years, and all had a good performance status (0 to 1). The observed overall response rate was 45%, comparable to younger patients (51%, p = 0.49). The estimated median progression-free survival (PFS) time and overall survival (OS) time were 8.7 and 19.3 months, respectively. These results did not significantly differ from those in younger patients (8.0 months for PFS (p = 0.58) and 19.7 months for OS (p = 0.94), respectively). The most common grade 3-4 adverse events included diarrhea (13%), fatigue (13%), peripheral neuropathy (10%), and neutropenia (7%). Moreover, the toxicity was never statistically different from that in younger patients. The efficacy of oxaliplatin-based combination was maintained in fit elderly patients ≥75 years.

Eumelanin Coating of Silica Aerogel by Supercritical Carbon Dioxide Deposition of a 5,6-Dihydroxyindole Thin Film.

Eumelanin integration in silica aerogel (SA) was achieved via supercritical adsorption of 5,6-dyhydroxyindole (DHI) from CO2. Notably, after the supercritical treatment, DHI evolved towards spontaneous polymerization, which resulted in uniform pigment development over the SA. The new material was characterized for its morphological and physicochemical properties, disclosing the formation of a eumelanin-like coating, as confirmed by UV⁻vis and electron paramagnetic resonance (EPR) spectroscopy.

The protective effect of the mesoporous host on the photo oxidation of fluorescent guests: a UV-Vis spectroscopy study.

The inclusion of fluorescent molecules within the pores of an inorganic host system is one of the most common ways used for the preparation of highly fluorescent nanosystems. The confinement of labile molecules usually leads to better performances mainly due to their protection against environmental parameters which can concur with the deactivation of the fluorescent ones. In this work the protective effect of the siliceous mesoporous host on photo oxidation of fluorescent guest molecules has been investigated under different experimental conditions, highlighting an outstanding photostability if compared to the performances exerted by the fluorescent dye in solution.

The cost-effectiveness of exenatide once weekly compared with exenatide twice daily and insulin glargine for the treatment of patients with type two diabetes and body mass index ≥30 kg/m(2) in Spain.

OBJECTIVE: The objective of this analysis was to estimate the cost-effectiveness of exenatide once weekly (EQW) for the treatment of type two diabetes mellitus (T2DM) in Spain. EQW was compared against exenatide twice daily (EBID) and insulin glargine (IG). METHODS: The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with T2DM treated with EQW, EBID, and IG. Treatment effects and patient baseline characteristics were taken from the DURATION 3 and pooled DURATION 1 and 5 studies, in the comparison against IG and EBID, respectively. Unit costs and health state utility values were derived from published sources. To reflect diabetes progression, patients started on EQW or EBID, switching to insulin glargine after 3 years. The analysis was conducted from the perspective of the Spanish National Health Service over a time horizon of 35 years with costs and outcomes discounted at 3%. The base case included patients with a BMI > 30 kg/m(2), which is in line with current prescription restrictions in Spain. Uncertainty was addressed through extensive one-way sensitivity analyses around key model parameters and a comprehensive probabilistic sensitivity analysis. RESULTS: When compared with EBID, EQW was the dominant strategy, i.e., less costly and more effective. When compared to IG, the incremental cost-effectiveness ratio was estimated at €12,084 per QALY gained. Sensitivity analysis indicated that the model projections were robust to the various scenarios tested. LIMITATIONS: Primary limitations of the analysis are common to other T2DM analyses and include the extrapolation of short-term clinical data to the 35 year time horizon and uncertainty around optimum treatment durations. CONCLUSION: The analyses indicate that EQW is a cost-effective option for the treatment of T2DM patients in Spain for patients with a BMI > 30 kg/m(2) considering a willingness-to-pay threshold of €30,000 per QALY gained.

Combined experimental and theoretical investigation of the hemi-squaraine/TiO2 interface for dye sensitized solar cells.

A simple hemi-squaraine dye (CT1) has been studied as a TiO2 sensitizer for application in dye sensitized solar cells (DSCs) by means of a combined experimental and theoretical investigation. This molecule is a prototype dye presenting an innovative anchoring group: the squaric acid moiety. Ab initio calculations based on Density Functional Theory (DFT) predict that this acid spontaneously deprotonates at the anatase (101) surface forming chemical bonds that are stronger than the ones formed by other linkers (e.g. cathecol and isonicotinic acid). Moreover an analysis of the electronic structure of the hybrid interface reveals the formation of a type II heterostructure ensuring adiabatic electron transfer from the molecule to the oxide. DSCs containing hemi-squaraine dyes were assembled, characterized and their performances compared to state of the art cells. Experimental results (large incident photon-to-electron conversion efficiency and an efficiency of 3.54%) confirmed the theoretical prediction that even a simple hemi-squaraine is an effective sensitizer for TiO2. Our study paves the way to the design of more efficient sensitizers based on a squaric acid linker and specifically engineered to absorb light in a larger part of the visible range.

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups.

BACKGROUND AND METHODS: Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10-30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles. RESULTS: We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles. CONCLUSION: These data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells.

Fluorescent silica nanoparticles improve optical imaging of stem cells allowing direct discrimination between live and early-stage apoptotic cells.

Highly bright and photostable cyanine dye-doped silica nanoparticles, IRIS Dots, are developed, which can efficiently label human mesenchymal stem cells (hMSCs). The application procedure used to label hMSCs is fast (2 h), the concentration of IRIS Dots for efficient labeling is low (20 µg mL(-1) ), and the labeled cells can be visualized by flow cytometry, confocal microscopy, and transmission electron microscopy. Labeled hMSCs are unaffected in their viability and proliferation, as well as stemness surface marker expression and differentiation capability into osteocytes. Moreover, this is the first report that shows nonfunctionalized IRIS Dots can discriminate between live and early-stage apoptotic stem cells (both mesenchymal and embryonic) through a distinct external cell surface distribution. On the basis of biocompatibility, efficient labeling, and apoptotic discrimination potential, it is suggested that IRIS Dots can serve as a promising stem cell tracking agent.

Bright photoluminescent hybrid mesostructured silica nanoparticles.

Bright photoluminescent mesostructured silica nanoparticles were synthesized by the incorporation of fluorescent cyanine dyes into the channels of MCM-41 mesoporous silica. Cyanine molecules were introduced into MCM-41 nanoparticles by physical adsorption and covalent grafting. Several photoluminescent nanoparticles with different organic loadings have been synthesized and characterized by X-ray powder diffraction, high resolution transmission electron microscopy and nitrogen physisorption porosimetry. A detailed photoluminescence study with the analysis of fluorescence lifetimes was carried out to elucidate the cyanine molecules distribution within the pores of MCM-41 nanoparticles and the influence of the encapsulation on the photoemission properties of the guests. The results show that highly stable photoluminescent hybrid materials with interesting potential applications as photoluminescent probes for diagnostics and imaging can be prepared by both methods.

Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles.

BACKGROUND: For a safe 'in vivo' biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases) play a pivotal role in the immune and inflammatory responses against exogenous toxins. Mastocytes are also recruited in the tumor stroma and are involved in tumor vascularization and growth. AIM AND METHODS: In this work, mastocyte-like rat basophilic leukemia (RBL) cells were used to investigate whether carboxyl-modified 30 nm polystyrene (PS) nanoparticles (NPs) and naked mesoporous silica (MPS) 10 nm NPs are able to label the secretory inflammatory granules, and possibly induce exocytosis of these granules. Uptake, cellular retention and localization of fluorescent NPs were analyzed by cytofluorometry and microscope imaging. RESULTS: OUR FINDINGS WERE THAT: (1) secretory granules of mastocytes are accessible by NPs via endocytosis; (2) PS and MPS silica NPs label two distinct subpopulations of inflammatory granules in RBL mastocytes; and (3) PS NPs induce calcium-dependent exocytosis of inflammatory granules. CONCLUSION: These findings highlight the value of NPs for live imaging of inflammatory processes, and also have important implications for the clinical use of PS-based NPs, due to their potential to trigger the unwanted activation of mastocytes.

Association of total serum cholesterol with functional outcome following home care rehabilitation in Italian patients with stroke.

BACKGROUND: Stroke is a disabling disease. In elderly populations, stroke is the third leading cause of death and the primary cause of reduction in or loss of functional ability and personal autonomy. Possible associations between levels of total serum cholesterol (TC) and both incidence of stroke and functional outcomes after rehabilitation are still under study. OBJECTIVE: To detect positive and negative prognostic factors associated with functional outcomes in first-time stroke patients admitted to an integrated home care rehabilitative program. METHODS: This study enrolled 141 patients with a first-time stroke who were admitted to a home care rehabilitation program. Primary outcome measures were the Barthel activities of daily living (ADL) and mobility indices at the beginning and end of the rehabilitative treatment. The impact of TC and other demographic and clinical variables was analyzed using bivariate and multivariate logistic regression analyses. RESULTS: Age and Short Portable Mental Status Questionnaire (SPMSQ) score were negatively associated with functional outcome. In contrast, elevated TC was positively associated with a better home rehabilitative treatment outcome. Barthel index score at admission was negatively associated with outcomes assessed by the Barthel ADL index and age with outcomes assessed by the Barthel mobility index. In a multivariate logistic regression analysis, SPMSQ score and elevated TC were significantly associated with outcome. Specifically, higher SPMSQ scores were negatively associated with better rehabilitative treatment outcomes, whereas elevated TC was positively associated. CONCLUSIONS: Elevated TC seems to be associated with better functional outcomes in patients with first-time stroke.

Primary amino-functionalized N-heterocyclic carbene ligands as support for Au(I)···Au(I) interactions: structural, electrochemical, spectroscopic and computational studies of the dinuclear [Au2(NH2(CH2)2imMe)2][NO3]2.

The N-heterocyclic carbene (NHC) precursor, 1-(2-aminoethyl)-3-methylimidazolium nitrate, [NH(2)(CH(2))(2)imMe)]NO(3) ([3][NO(3)]) reacted with Ag(2)CO(3) in dimethyl sulfoxide readily yielding a Ag(I)-(NHC-NH(2)) complex presenting limited stability in solution. The in situ carbene transfer reaction of the latter with [Au(tht)Cl] afforded the first example of a dinuclear gold(I) complex [Au(2)(NH(2)(CH(2))(2)imMe)(2)][NO(3)](2) ([5][NO(3)](2)) bearing a primary amino-functionalized NHC ligand. The complex has been characterized by NMR, mass spectrometry, X-ray crystallography and cyclic voltammetry; the electrochemical behaviour and photophysical properties of [5][NO(3)](2) have been also investigated and the experimental data have been compared with density functional theory (DFT) and Time Dependent (TDDFT) calculations. Single-crystal structural studies showed that the Au(I)-carbene compound contains dinuclear (AuL)(2) cations in which pairs of gold(I) centres are linked by a pair of bridging ligands, with a Au···Au aurophilic contact of 3.2332(17) Å that is maintained in solution as documented by the DFT calculations. Complex [5][NO(3)](2) is photoluminescent in solution at room temperature and the high energy emission peak at 410 nm is remarkably shifted with respect to the absorption band centered at 260 nm.

Colonization of pressure ulcers by multidrug-resistant microorganisms in patients receiving home care.

Colonization and/or infection with multidrug-resistant microorganisms (MDRO) of pressure ulcers in patients receiving care at home have seldom been investigated. The objective of this study was to assess the prevalence of MDRO colonization in pressure ulcers of patients receiving home care in Palermo, Italy. Vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and multidrug-resistant Gram-negative bacilli (MDRGN) were isolated, identified, and characterized from pressure ulcers and selected home environment surfaces. Thirty-two patients were enrolled, of whom 12 were under antimicrobial therapy. Five patients had been admitted to hospital in the preceding year. Nineteen patients tested positive for 1 or more MDROs. In particular, 1 patient was colonized by a vanA-containing strain of VRE, 5 by MRSA, and 17 by MDRGN of different species. Our findings suggest that pressure ulcers in home care patients could play a role in bringing MDROs into the community setting.

Behaviour of fluorescence emission of cyanine dyes, cyanine based fluorescent nanoparticles and CdSe/ZnS quantum dots in water solution upon specific thermal treatments.

Fluorescence techniques are widely used as detection methods in a wide range of biological imaging and analytical applications. The purpose of this work is to determine a measurement method which leads to a comparison between different classes of fluorophores in term of stability of the fluorescence signal upon thermal treatment cycles. This kind of investigation can determine whether the fluorophore performance is affected by heating/cooling cycles and to what extent. The fluorophores considered in this work were organic fluorophores belonging to the family of indocyanine dyes (IRIS3 by Cyanine Technologies S.p.A.) in their molecular form or encapsulated within silica nanoparticles, and CdSe/ZnS carboxyl quantum dots (Qdots 565 ITK by Invitrogen). The NIST Standard Reference Material® SRM 1932 fluorescein solution was used in the certified concentration as reference material in order to evaluate the repeatability of the used spectrofluorimeter. The proposed measurement protocol allows to characterize all kind of fluorophores upon thermal treatments. This allows direct comparison of their performance under temperature changes, giving useful guidelines for the selection of the most suitable fluorophore for the envisaged application. Moreover the method appears to be a promising tool for the characterisation of reference fluorescent materials. The experimental results demonstrate that each fluorophore class shows a specific behaviour. The experimental data analysis points out an important hysteresis effect for quantum dots that was not detected for cyanine molecules and was only slightly detected for cyanine doped silica nanoparticles.

Photoactive Ru complex embedded in mesostructured MCM-41 nanoparticles.

The synthesis and characterization of photoactive hybrid materials based on [Ru(bpy)(3)](2+) physically adsorbed within the channels of mesoporous MCM-41 silica nanoparticles is presented. A set of photoactive mesostructured hybrids with different guest loading has been prepared and characterized by X-ray diffraction, High Resolution Transmission Electron Microscopy, volumetric analyses, Diffuse Reflectance UV-Vis and Photoluminescence spectroscopies and lifetime measurements. The hybrids synthesis and the washing procedures, performed to investigate the host-guest interaction and the stability of the complex within the mesopores, didn't affect the integrity of the structure and morphology of MCM-41 nanoparticles. The dispersion of [Ru(bpy)(3)](2+) within the channels varied depending on the loading value and this is reflected in the different and peculiar photoluminescence features of the resulting hybrid materials. Photoluminescence spectroscopy evidenced that the use of MCM-41 nanoparticles ensures a better dispersion of the complex within the mesopores, if compared with traditional MCM-41. Further studies are in progress to investigate the interesting and promising features exhibited by such photoactive systems for advanced applications of electrochemiluminescence in optoelectronics and diagnostics.

Depression and recovery of daily life autonomy in patients with stroke receiving home rehabilitative treatment.

BACKGROUND: The object of this study was to evaluate the prevalence of post stroke depression and its possible role as a predictive negative factor in patients receiving home rehabilitation treatment. METHODS: We analyzed 103 patients with stroke by correlating comorbidities, clinical and blood test parameters and characteristics of the lesion with depression class identified according to the Hamilton scale and the outcome of the rehabilitation program. RESULTS: A significant association between hypertension and post-stroke severe depression emerged in the female patients. CONCLUSIONS: Since the literature offers conflicting data, our results may contribute a stimulus for further studies. KEYWORDS: Home care; Rehabilitation; Stroke; Depression; Hypertension.

Photoactive hybrid nanomaterials: indocyanine immobilized in mesoporous MCM-41 for "in-cell" bioimaging.

Mesoporous silica nanoparticles are being explored as versatile tools for various biomedical and biotechnological applications including disease diagnosis, drug delivery, and intracellular imaging. In this paper, the synthesis and characterization of a fluorescent hybrid mesoporous silica nanomaterial, which is noncytotoxic and shows great potential for "in-cell" bioimaging applications, will be described. The hybrid mesoporous material has been obtained by confining highly fluorescent organic dyes, belonging to the indocyanine family, within the channels of mesoporous MCM-41. To explore the dispersion of the dye inside the mesoporous channels and the formation of dye aggregates, several hybrid samples with increasing dye/MCM-41 loading (up to 100 mg/g) were prepared. A uniform distribution of monomeric 1,1'-diethyl-3,3,3',3'-tetramethylindocarbocyanine iodide has been achieved at low dye loading (1 mg/g), as evidenced by photoluminescence spectra and lifetime, while a progressive formation of J-aggregates is induced by an increase in the dye loading. To elucidate the properties of the dye immobilized in mesoporous MCM-41, a detailed physical chemical characterization by structural (X-ray diffraction), volumetric and optical (Fourier transform infrared, diffuse-reflectance UV-vis and photoluminescence) techniques has been performed. By ultrasonication of the bulk material, nanoparticles of 2-20 nm diameter were obtained. Biocompatibility, endocytic uptake, and intracellular compartmentalization of such fluorescent nanoparticles were investigated in mammalian cultured cells.