Periodontal regeneration is still a challenge for periodontists and tissue engineers, as it requires the simultaneous restoration of different tissues—namely, cementum, gingiva, bone, and periodontal ...ligament (PDL). Here, we synthetized a chitosan (CH)–based trilayer porous scaffold to achieve periodontal regeneration driven by multitissue simultaneous healing. We produced 2 porous compartments for bone and gingiva regeneration by cross-linking with genipin either medium molecular weight (MMW) or low molecular weight (LMW) CH and freeze-drying the resulting scaffolds. We synthetized a third compartment for PDL regeneration by CH electrochemical deposition; this allowed us to produce highly oriented microchannels of about 450-µm diameter intended to drive PDL fiber growth toward the dental root. In vitro characterization showed rapid equilibrium water content for MMW-CH and LMW-CH compartments (equilibrium water content after 5 min >85%). The MMW-CH compartment degraded more slowly and provided significantly more resistance to compression (28% ± 1% of weight loss at 4 wk; compression modulus HA = 18 ± 6 kPa) than the LMW-CH compartment (34% ± 1%; 7.7 ± 0.8 kPa) as required to match the physiologic healing rates of bone and gingiva and their mechanical properties. More than 90% of all human primary periodontal cell populations tested on the corresponding compartment survived during cytocompatibility tests, showing active cell metabolism in the alkaline phosphatase and collagen deposition assays. In vivo tests showed high biocompatibility in wild-type mice, tissue ingrowth, and vascularization within the scaffold. Using the periodontal ectopic model in nude mice, we preseeded scaffold compartments with human gingival fibroblasts, osteoblasts, and PDL fibroblasts and found a dense mineralized matrix within the MMW-CH region, with weakly mineralized deposits at the dentin interface. Together, these results support this resorbable trilayer scaffold as a promising candidate for periodontal regeneration.
Bioactive glass (BG) based scaffolds (45S5 BG composition) were developed by the replica technique using natural marine sponges as sacrificial templates. The resulting scaffolds were characterized by ...superior mechanical properties (compression strength up to 4 MPa) compared to conventional BG scaffolds prepared using polyurethane (PU) packaging foam as a template. This result was ascribed to a reduction of the total scaffold porosity without affecting the pore interconnectivity (>99%). It was demonstrated that the reduction of total porosity did not affect the bioactivity of the BG-based scaffolds, tested by immersion of scaffolds in simulated body fluid (SBF). After 1 day of immersion in SBF, a homogeneous CaP deposit on the surface of the scaffolds was formed, which evolved over time into carbonate hydroxyapatite (HCA). Moreover, the enhanced mechanical properties of these scaffolds were constant over time in SBF; after an initial reduction of the maximum compressive strength upon 7 days of immersion in SBF (to 1.2 ± 0.2 MPa), the strength values remained almost constant and higher than those of BG-based scaffolds prepared using PU foam (<0.05 MPa). Preliminary cell culture tests with Saos-2 osteoblast cell line, namely direct and indirect tests, demonstrated that no toxic residues remained from the natural marine sponge templates and that cells were able to proliferate on the scaffold surfaces.
A Tissue-Equivalent Proportional Counter (TEPC), based on a single GEM foil of standard geometry, has been tested with pure propane gas at low pressure, in order to simulate a tissue site of about ...1µm equivalent size. In this work, the performance of GEM with propane gas at a pressure of 21 and 28kPa will be presented. The effective gas gain was measured in various conditions using a 244Cm alpha source. The dependence of effective gain on the electric field strength along the GEM channel and in the drift and induction region was investigated. A maximum effective gain of about 5×103 has been reached. Results obtained in pure propane gas are compared with gas gain measurements in gas mixtures commonly employed in microdosimetry, that is propane and methane based Tissue-Equivalent gas mixtures.
The REMIX project is focused on the cyclotron-based production of 47Sc, 149Tb, 152Tb, 155Tb and 161Tb radionuclides, whose decay characteristics make them suitable for medical applications. This work ...will outline the main results achieved withing the REMIX collaboration, that is organized in the following Work Packages (WP): WP1. Target manufacturing (49Ti, 50Ti and 155Gd2O3) and characterization; WP2. Nuclear cross section (XS) measurements with 49Ti and 50Ti targets for 47Sc production; WP3. Nuclear XS measurements with natDy, 159Tb and natEu targets for xxTb production; WP4. Nuclear XS modeling for 47Sc and 155Tb production; WP5. Dosimetric calculations for 47Sc- and xxTb-labelled radiopharmaceuticals; WP6. 155Tb Thick Target Yield (TTY) measurements; WP7. Apparatus design and realization for irradiation tests with the LARAMED beamline. Since the LARAMED bunkers and ancillary laboratories are currently under completion at the INFN-LNL, the nuclear XS experiments are carried out in collaboration with the GIP ARRONAX facility (Saint-Herblain, France) and the Thick Target Yield (TTY) measurements are performed at the Sacro Cuore Don Calabria hospital (SCDCh, Negrar, Verona, Italy).
A multi-element tissue-equivalent proportional counter (TEPC), based on a gas electron multiplier, has been constructed with several cavities of small dimensions (down to 0.5 mm of diameter), to be ...used for microdosimetric measurements in intense, pulsed, radiation fields. First micro- and nano-dosimetric spectra with low-energy X rays in various simulated tissue site sizes are presented. The specific advantages and the calibration methods of this type of TEPC are discussed.
Mutations in MAPK signalling genes are driver events in melanoma, and have therapeutic relevance in the metastatic and adjuvant setting. This study evaluated the intra-patient heterogeneity of BRAF, ...NRAS and c-KIT mutational status between 30 primary melanomas and 39 related metastases, using molecular analysis and immunohistochemistry. BRAF mutations were identified in 46.7% of primary melanomas and 48.7% of metastases and NRAS mutations in 20% and 25.6%, respectively. Intra-patient heterogeneity was detected in 13.3% of patients for both BRAF and NRAS genes and was not associated with clinico-pathological characteristics of melanomas or metastases. High consistency was observed between immunostaining and molecular methods for BRAFV600E (k = 0.90; p < 0.001) and NRASQ61R (k = 0.87; p < 0.001). These findings demonstrate a relevant intra-patient heterogeneity between primary and metastatic lesions that is independent of clinical variables and methodological approach.
Aims
The aim of this study was to develop a new class of gallium (Ga)‐doped chitosan (CS) coatings fabricated by electrophoretic deposition (EPD) in staphylococcal infection therapy.
Methods and ...Results
Biofilm formation on EPD CS/Ga coatings by Staphylococcus epidermidis and Staphylococcus aureus, which are the main strains involved in postarthroplasty infections, was assessed. The codeposition of an antibacterial agent was effective; Ga loaded into CS matrix reduces biofilm viability by up to 86% and 80% for S. epidermidis and S. aureus strains respectively. Lastly, the influence of pulsed electromagnetic field (PEMF) on the bactericidal activity of CS/Ga coatings was investigated in vitro. To this end, the coatings were incubated with S. epidermidis and S. aureus and exposed to the PEMF using two different frequencies and times. Biofilm viability for S. epidermidis was decreased by 35–40% in the presence of low‐frequency (LF) and high‐frequency (HF) PEMF respectively. Biofilm viability by S. aureus was not further reduced in the presence of LF PEMF, but decreased by 38% at HF PEMF.
Conclusions
This study has established that a combination of PEMFs with the antibacterial agent improves bactericidal activity of Ga against S. epidermidis strain 14990 and S. aureus strain 12600.
Significance and Impact of the Study
This new integrated approach could reduce the incidence of infection in orthopaedic implant applications. It also clearly demonstrates that the combination of Ga treatment with PEMF could aid biofilm‐associated infection therapy due to improved Ga efficiency.
To study the track structure of light ions, a measuring device has been developed at the Legnaro National Laboratory of INFN, which can be used to investigate separately the penumbra region of ...particle tracks and the track-core region, which is a few nanometres in diameter. The device is based on single-electron counting techniques by means of a gas detector; it simulates a 'nanometre-sized' biological volume of about 20 nm in diameter that can be moved with respect to a narrow particle beam to measure the ionization-cluster-size distributions caused within the target volume by the passage of single primary particles, as a function of the impact parameter. To investigate the ionization-cluster-size formation caused by primary particles of medical interest when they penetrate through or pass by the target volume at a specified impact parameter, measurements and Monte Carlo simulations were performed for 20 MeV protons, 16 MeV deuterons, 48 MeV 6Li-ions, 26.7 MeV 7Li-ions and 96 MeV 12C-ions. The detailed analysis of the resulting distributions showed that in the track-core region their shape is mainly determined by the mean free ionization path length of the primary particles, whereas in the penumbra region the shape of the distributions is almost independent of the impact parameter, and also of the particle type and velocity.
A multi-element tissue-equivalent proportional counter (TEPC), based on a single gas electron multiplier (GEM) foil of standard geometry, has been constructed with 16 cylindrical sensitives volumes. ...In this article, the design of this novel counter is described and first microdosimetric measurements are presented. To study the response of the GEM-TEPC to both low and high linear energy transfer radiation fields, the microdosimetric spectra due to a 137Cs gamma-ray source and to fast neutrons from 7Li(d,n)8Be reaction have been measured using pure propane gas at low pressure, in order to simulate a tissue site of about 1 µm equivalent size. The comparison with spectra measured with a spherical TEPC and with a mini-TEPC demonstrates promising properties for application of the GEM-TEPC for microdosimetric applications.
Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab ...in a real-world setting are scarce.
A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts.
A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16.
This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.
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