Synthesis of Bodipy-Tagged Galactoconjugates and Evaluation of Their Antibacterial Properties.

As a development of our research on biocompatible glycoconjugate probes and specifically multi-chromophoric systems, herein, we report the synthesis and early bactericidal tests of two luminescent glycoconjugates whose basic structure is characterized by two boron dipyrromethene difluoride (BODIPY) moieties and three galactoside rings mounted on an oligophenylene ethynylene (OPE) skeleton. BODIPY fluorophores have found widespread application in many branches of biology in the last few decades. In particular, molecular platforms showing two different BODIPY groups have unique photophysical behavior useful in fluorescence imaging. Construction of the complex architecture of the new probes is accomplished through a convergent route that exploits a series of copper-free Heck-Cassar-Sonogashira cross-couplings. The great emergency due to the proliferation of bacterial infections, in conjunction with growing antibiotic resistance, requires the production of new multifunctional drugs and efficient methods for their targeted delivery to control bacteria-associated diseases. Preliminary studies of the glycoconjugate properties as antibacterial agents against representatives of Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) pathogens, which are associated with chronic infections, indicated significant bactericidal activity ascribable to their structural features.

Polyvinylalcohol Composite Filled with Carbon Dots Produced by Laser Ablation in Liquids.

Carbon dots (CDs), owing to their excellent photoluminescent features, have been extensively studied for physics preparation methods and for biomedical and optoelectronic device applications. The assessment of the applicability of CDs in the production of luminescent polymeric composites used in LEDs, displays, sensors, and wearable devices is being pursued. The present study reports on an original, environmentally friendly, and low-cost route for the production of carbon dots with an average size of 4 nm by laser ablation in liquid. Jointly, to prove the significance of the study for a wide range of applications, a free-standing flexible polyvinyl alcohol (PVA) composite containing photoluminescent carbon dots was manufactured. CDs were prepared using targets of porose charcoal with a density of 0.271 g/cm3 placed in phosphate-buffered saline (PBS) liquid solution and irradiated for 30 min by pulsed IR diode laser. The optical properties of the obtained suspension containing carbon dots were studied with UV-ViS and FTIR spectroscopies. The photoluminescence of the produced carbon dots was confirmed by the emission peak at 480 nm in the luminescence spectrum. A narrow luminescence band with a full width at half-maximum (FWHM) of less than 40 nm could be an asset in spectral emission analysis in different applications. Atomic force microscopy confirms the feasibility of manufacturing CDs in clean and biocompatible environments, paving the way for an easier and faster production route, crucial for their wider applicability.

Anti-Biofilm Strategies: A Focused Review on Innovative Approaches.

Biofilm (BF) can give rise to systemic infections, prolonged hospitalization times, and, in the worst case, death. This review aims to provide an overview of recent strategies for the prevention and destruction of pathogenic BFs. First, the main phases of the life cycle of BF and maturation will be described to identify potential targets for anti-BF approaches. Then, an approach acting on bacterial adhesion, quorum sensing (QS), and the extracellular polymeric substance (EPS) matrix will be introduced and discussed. Finally, bacteriophage-mediated strategies will be presented as innovative approaches against BF inhibition/destruction.

Anterior Cruciate Ligament Repair Augmented With Dynamic Intraligamentary Stabilization Is Equivalent to Hamstring Autograft Reconstruction at Short- and Mid-Term Follow-Up: A Systematic Review.

PURPOSE: To compare clinical outcomes, knee stability and complications, failure, and revision rates after anterior cruciate ligament repair (ACLr) with dynamic intraligamentary stabilization (DIS) versus anterior cruciate ligament reconstruction (ACLR) with hamstring autograft for primary ACL ruptures at short and mid-term follow-up. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of PubMed/MEDLINE and Scopus was performed. Studies that evaluated patients undergoing ACLr with DIS or ACLR with hamstring autograft were considered for inclusion. Studies were excluded if patients were affected by concomitant meniscal, ligamentous, or chondral injuries needing surgical treatment, because of their potential confounding effect on postoperative outcomes. The Risk of Bias-2 tool was used to assess the risk of bias in the included studies. The quality of available evidence was rated according to Grading of Recommendations Assessment, Development, and Evaluation recommendations. The study protocol was registered in the PROSPERO database (ID: CRD42023394558). RESULTS: Five randomized controlled trials comparing the outcomes of ACLr with DIS versus ACLR with hamstring autograft met the inclusion criteria. No major differences in terms of patient-reported outcomes (International Knee Documentation Committee subjective form, Lysholm score, Tegner activity scale, Knee injury and Osteoarthritis Outcome Score, visual analog scale satisfaction) or rates of complications, revisions, and failures were found in included studies at all time points. Repair showed greater International Knee Documentation Committee subjective form scores at 5 years in one study, whereas ACLR displayed significantly increased knee stability at 6 months and 5 years in 2 different studies, although the clinical relevance of these differences is doubtful. CONCLUSIONS: The results of this study suggest that ACLr with DIS is not inferior to ACLR with hamstring autograft in terms of rates of clinical outcomes, knee stability, risk of failure, complications, and revision surgery. Therefore, ACLr with DIS may be a viable alternative to ACLR with hamstring autograft in selected patients. LEVEL OF EVIDENCE: Level I, systematic review of Level I studies.

A Novel Serum-Based Diagnosis of Alzheimer's Disease Using an Advanced Phage-Based Biochip.

55 million people worldwide suffer from Alzheimer's disease (AD). A definitive diagnosis of AD is made postmortem after a neuropathological examination of the brain. There is an urgent need for an innovative, noninvasive methodology that allows for an early and reliable diagnosis. Several engineered phages that recognized Aß-autoantibodies present in the sera of AD patients are previously identified. Here, novel phages are tested for their ability to accurately discriminate AD sera using immunophage-polymerase chain reaction in a miniatured biochip. It is found that five of the six phages analyzed discriminate between healthy controls and AD patients. Further, by combining the response of two phages, non-AD and severe AD cases are identified with 100% accuracy and mild-to-moderate cases with 90% accuracy. While the number of cases used here are relatively small and can be confirmed in larger cohorts, this first-of-a-kind system represents an innovative methodology with the potential of having a major impact in the AD field: from a clinical perspective, it can aid physicians in making an accurate AD diagnosis; from a research perspective, it can be used as a surrogate for AD clinical trials.

Biological Response Evaluation of Human Fetal Osteoblast Cells and Bacterial Cells on Fractal Silver Dendrites for Bone Tissue Engineering.

Prosthetic joint replacement is the most widely used surgical approach to repair large bone defects, although it is often associated with prosthetic joint infection (PJI), caused by biofilm formation. To solve the PJI problem, various approaches have been proposed, including the coating of implantable devices with nanomaterials that exhibit antibacterial activity. Among these, silver nanoparticles (AgNPs) are the most used for biomedical applications, even though their use has been limited by their cytotoxicity. Therefore, several studies have been performed to evaluate the most appropriate AgNPs concentration, size, and shape to avoid cytotoxic effects. Great attention has been focused on Ag nanodendrites, due to their interesting chemical, optical, and biological properties. In this study, we evaluated the biological response of human fetal osteoblastic cells (hFOB) and P. aeruginosa and S. aureus bacteria on fractal silver dendrite substrates produced by silicon-based technology (Si_Ag). In vitro results indicated that hFOB cells cultured for 72 h on the Si_Ag surface display a good cytocompatibility. Investigations using both Gram-positive (S. aureus) and Gram-negative (P. aeruginosa) bacterial strains incubated on Si_Ag for 24 h show a significant decrease in pathogen viability, more evident for P. aeruginosa than for S. aureus. These findings taken together suggest that fractal silver dendrite could represent an eligible nanomaterial for the coating of implantable medical devices.

Antimicrobial and Antibiofilm Photodynamic Action of Photosensitizing Nanoassemblies Based on Sulfobutylether-ß-Cyclodextrin.

Developing new broad-spectrum antimicrobial strategies, as alternatives to antibiotics and being able to efficiently inactivate pathogens without inducing resistance, is one of the main objectives in public health. Antimicrobial photodynamic therapy (aPDT), based on the light-induced production of reactive oxygen species from photosensitizers (PS), is attracting growing interest in the context of infection treatment, also including biofilm destruction. Due to the limited photostability of free PS, delivery systems are increasingly needed in order to decrease PS photodegradation, thus improving the therapeutic efficacy, as well as to reduce collateral effects on unaffected tissues. In this study, we propose a photosensitizing nanosystem based on the cationic porphyrin 5,10,15,20-tetrakis (N-methyl- 4-pyridyl)-21H,23H-porphyrin (TMPyP), complexed with the commerical sulfobutylether-beta-cyclodextrin (CAPTISOL®), at a 1:50 molar ratio (CAPTISOL®/TMPyP)50_1. Nanoassemblies based on (CAPTISOL®/TMPyP)50_1 with photodynamic features exhibited photo-antimicrobial activity against Gram-negative and Gram-positive bacteria. Moreover, results from P. aeruginosa reveal that CAPTISOL® alone inhibits pyocyanin (PYO) production, also affecting bacterial biofilm formation. Finally, we obtained a synergistic effect of inhibition and destruction of P. aeruginosa biofilm by using the combination of CAPTISOL® and TMPyP.

Supramolecular assemblies based on polymeric cyclodextrin nanosponges and a cationic porphyrin with antimicrobial photodynamic therapy action.

Within of the increasing requirement of alternative approaches to fight emerging infections, nano-photosensitisers (nanoPS) are currently designed with the aim to optimize the antimicrobial photodynamic (aPDT) efficacy. The utilize of less expensive nanocarriers prepared by simple and eco-friendly methodologies and commercial photosensitisers are highly desiderable. In this direction, here we propose a novel nanoassembly composed of water soluble anionic polyester ß-CD nanosponges (ß-CD-PYRO hereafter named ßNS) and the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4- yl)porphine (TMPyP). Nanoassemblies were prepared in ultrapure water by mixing PS and ßNS, by exploiting their mutual electrostatic interaction, and characterized by various spectroscopic techniques such as UV/Vis, Steady-State and Time Resolved Fluorescence, Dynamic Light Scattering and ζ-potential. NanoPS produce appreciable amount of single oxygen similar to free porphyrin and a prolonged stability after 6 days of incubations in physiological conditions and following photoirradiation. Antimicrobial photodynamic action against fatal hospital-acquired infections such as P. aeruginosa and S. aureus was investigated by pointing out the ability of cationic porphyrin loaded- CD nanosponges to photo-kill bacterial cells at prolonged time of incubation and following irradiation (MBC99 = 3.75 µM, light dose = 54.82 J/cm2).

Structural and antibacterial studies of novel ZnO and ZnxMn(1-x)O nanostructured titanium scaffolds for biomedical applications.

In the biomedical field, the demand for the development of broad-spectrum biomaterials able to inhibit bacterial growth is constantly increasing. Chronic infections represent the most serious and devastating complication related to the use of biomaterials. This is particularly relevant in the orthopaedic field, where infections can lead to implant loosening, arthrodesis, amputations and sometimes death. Antibiotics are the conventional approach for implanted-associated infections, but they have the limitation of increasing antibiotic resistance, a critical worldwide healthcare issue. In this context, the development of anti-infective biomaterials and infection-resistant surfaces can be considered the more effective strategy to prevent the implant colonisation and biofilm formation by bacteria, so reducing the occurrence of implant-associated infections. In the last years, inorganic nanostructures have become extremely appealing for chemical modifications or coatings of Ti surfaces, since they do not generate antibiotic resistance issues and are featured by superior stability, durability, and full compatibility with the sterilization process. In this work, we present a simple, rapid, and cheap chemical nanofunctionalization of titanium (Ti) scaffolds with colloidal ZnO and Mn-doped ZnO nanoparticles (NPs), prepared by a sol-gel method, exhibiting antibacterial activity. ZnO NPs and ZnxMn(1-x)O NPs formation with a size around 10-20nm and band gap values of 3.42 eV and 3.38 eV, respectively, have been displayed by characterization studies. UV-Vis, fluorescence, and Raman investigation suggested that Mn ions acting as dopants in the ZnO lattice. Ti scaffolds have been functionalized through dip coating, obtaining ZnO@Ti and ZnxMn(1-x)O@Ti biomaterials characterized by a continuous nanostructured film. ZnO@Ti and ZnxMn(1-x)O@Ti displayed an enhanced antibacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) bacterial strains, compared to NPs in solution with better performance of ZnxMn(1-x)O@Ti respect to ZnO@Ti. Notably, it has been observed that ZnxMn(1-x)O@Ti scaffolds reach a complete eradication for S. aureus and 90 % of reduction for P. aeruginosa. This can be attributed to Zn2+ and Mn2+ metal ions release (as observed by ICP MS experiments) that is also maintained over time (72 h). To the best of our knowledge, this is the first study reported in the literature describing ZnO and Mn-doped ZnO NPs nanofunctionalized Ti scaffolds with improved antibacterial performance, paving the way for the realization of new hybrid implantable devices through a low-cost process, compatible with the biotechnological industrial chain method.

CINSARC in high-risk soft tissue sarcoma patients treated with neoadjuvant chemotherapy: Results from the ISG-STS 1001 study.

BACKGROUND: The Complexity INdex in SARComas (CINSARC) is a transcriptional signature derived from the expression of 67 genes involved in mitosis control and chromosome integrity. This study aims to assess CINSARC value of in an independent series of high-risk patients with localized soft tissue sarcoma (STS) treated with preoperative chemotherapy within a prospective, randomized, phase III study (ISG-STS 1001). PATIENTS AND METHODS: Patients with available pre-treatment samples, treated with 3 cycles of either standard (ST) preoperative or histotype-tailored (HT) chemotherapy, were scored according to CINSARC (low-risk, C1; high-risk, C2). The 10-year overall survival probability (pr-OS) according to SARCULATOR was calculated, and patients were classified accordingly (low-risk, Sarc-LR, 10-year pr-OS>60%; high-risk, Sarc-HR, 10-year pr-OS<60%). Survival functions were estimated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Eighty-six patients were included, 30 C1 and 56 C2, 49 Sarc-LR and 37 Sarc-HR. A low level of agreement between CINSARC and SARCULATOR was observed (Cohen's Kappa = 0.174). The 5-year relapse-free survival in C1 and C2 were 0.57 and 0.55 (p = 0.481); 5-year metastases-free survival 0.63 and 0.64 (p = 0.740); 5-year OS 0.80 and 0.72 (p = 0.460). The 5-year OS in C1 treated with ST and HT chemotherapy was 0.84 and 0.76 (p = 0.251) respectively; in C2 treated it was 0.72 and 0.70 (p = 0.349). The 5-year OS in Sarc-LR treated with S and HT chemotherapy was 0.80 and 0.82 (p = 0.502) respectively; in Sarc-HR it was 0.70 and 0.61 (p = 0.233). CONCLUSIONS: Our results, although constrained by the small size of the series, suggest that CINSARC has weak prognostic power in high-risk, localized STS treated with neoadjuvant chemotherapy.

Metal-Based Nanoparticles: Antibacterial Mechanisms and Biomedical Application.

The growing increase in antibiotic-resistant bacteria has led to the search for new antibacterial agents capable of overcoming the resistance problem. In recent years, nanoparticles (NPs) have been increasingly used to target bacteria as an alternative to antibiotics. The most promising nanomaterials for biomedical applications are metal and metal oxide NPs, due to their intrinsic antibacterial activity. Although NPs show interesting antibacterial properties, the mechanisms underlying their action are still poorly understood, limiting their use in clinical applications. In this review, an overview of the mechanisms underlying the antibacterial activity of metal and metal oxide NPs will be provided, relating their efficacy to: (i) bacterial strain; (ii) higher microbial organizations (biofilm); (iii) and physico-chemical properties of NPs. In addition, bacterial resistance strategies will be also discussed to better evaluate the feasibility of the different treatments adopted in the clinical safety fields. Finally, a wide analysis on recent biomedical applications of metal and metal oxide NPs with antibacterial activity will be provided.

Physicochemical Characterization and Antibacterial Properties of Carbon Dots from Two Mediterranean Olive Solid Waste Cultivars.

Carbon nanomaterials have shown great potential in several fields, including biosensing, bioimaging, drug delivery, energy, catalysis, diagnostics, and nanomedicine. Recently, a new class of carbon nanomaterials, carbon dots (CDs), have attracted much attention due to their easy and inexpensive synthesis from a wide range of precursors and fascinating physical, chemical, and biological properties. In this work we have developed CDs derived from olive solid wastes of two Mediterranean regions, Puglia (CDs_P) and Calabria (CDs_C) and evaluated them in terms of their physicochemical properties and antibacterial activity against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Results show the nanosystems have a quasi-spherical shape of 12-18 nm in size for CDs_P and 15-20 nm in size for CDs_C. UV-Vis characterization indicates a broad absorption band with two main peaks at about 270 nm and 300 nm, respectively, attributed to the π-π* and n-π* transitions of the CDs, respectively. Both samples show photoluminescence (PL) spectra excitation-dependent with a maximum at λem = 420 nm (λexc = 300 nm) for CDs_P and a red-shifted at λem = 445 nm (λexc = 300 nm) for CDs_C. Band gaps values of ≈ 1.48 eV for CDs_P and ≈ 1.53 eV for CDs_C are in agreement with semiconductor behaviour. ζ potential measures show very negative values for CDs_C compared to CDs_P (three times higher, -38 mV vs. -18 mV at pH = 7). The evaluation of the antibacterial properties highlights that both CDs have higher antibacterial activity towards Gram-positive than to Gram-negative bacteria. In addition, CDs_C exhibit bactericidal behaviour at concentrations of 360, 240, and 120 µg/mL, while lesser activity was found for CDs_P (bacterial cell reduction of only 30% at the highest concentration of 360 µg/mL). This finding was correlated to the higher surface charge of CDs_C compared to CDs_P. Further investigations are in progress to confirm this hypothesis and to gain insight on the antibacterial mechanism of both cultivars.

Dual-Functional Nano-Functionalized Titanium Scaffolds to Inhibit Bacterial Growth and Enhance Osteointegration.

Implantable biomaterials play a key role for the success of orthopedic surgery procedures. However, infections remain one of the most damaging post-operative complications that lead to the implant failure. Recently, several approaches have been proposed to avoid or manage implant-associated infections. Among these, an appropriate surface functionalization to confer intrinsic antibacterial properties preserving the osteo-integration ability represents an appealing strategy for the development of innovative implant materials. Titanium and its alloys are the most used materials for manufacturing of both articular and bone skull prostheses as well as dental implants. However, to date there is still a significant clinical need to improve their bioactivity, osseointegration and antibacterial activity. In this study, titanium biomimetic scaffolds are prepared by nano-functionalization with TiO2 (Ti_TiO2) and γFe2O3 (Ti_γFe2O3). Both cytocompatibility and antibacterial activity have been evaluated. Data show that both nano-functionalized scaffolds exhibit a good antibacterial activity towards Staphylococcus aureus, reducing colony number to 99.4% (Ti_TiO2) and 99.9% (Ti_γFe2O3), respectively. In addition, an increase of both human adipose-derived mesenchymal stem cells (hADSCs) cell proliferation (up to 4.3-fold for Ti_TiO2 and 3.7-fold for Ti_γFe2O3) and differentiation has been observed. These data suggest that these nano-functionalized titanium substrates represent promising prototypes for new antimicrobial and osteoconductive biomaterials to be used in the orthopedic field to reconstruct significant bone defect.

A multivariate analysis of Multiple Myeloma subtype plasma cells.

Trusted methods for identifying different Multiple Myeloma (MM) cells and their biological diversity due to their immunophenotypic variety are often little detailed and difficult to find in literature. In this work, we show that micro-Raman spectroscopy can be used to highlight if there is a certain degree of distinction or correlation between the MM subtype plasmacells in relation to the cluster of differentiation (CD45+/CD38+/CD138-) and (CD45-/CD38+/CD138+). After taking samples from the bone marrow of patients with Multiple Myeloma, the PCs were sorted by flow cytometry, selecting the most common CD of the disease, i.e. CD 45, CD38 and CD138. Some spectral differences are observed comparing the Raman spectra of the two set of samples investigated. To better define in which spectral regions there are greater differences and, therefore, to which biological contributions the changes refers, we also explored the principal component analysis (PCA) of the collected Raman data. The spectral variations between the different sorted cells have been highlighted by plotting loading vectors PC1 and PC2, which shows a net differentiation between the two set of cells. Ultimately, the differences shown by PCA have been associated with the spectral variations observed and explained in terms of changes of proteins and lipid contributions. Thus, the differentiation of Multiple Myeloma subtype plasma cells by confocal micro-Raman spectroscopy can be proposed as a diagnostic tool in the speeding up of cell identification, assessing the intracellular biochemical changes that take place in cancer cells.

Role of Phage Capsid in the Resistance to UV-C Radiations.

The conformational variation of the viral capsid structure plays an essential role both for the environmental resistance and acid nuclear release during cellular infection. The aim of this study was to evaluate how capsid rearrangement in engineered phages of M13 protects viral DNA and peptide bonds from damage induced by UV-C radiation. From in silico 3D modelling analysis, two M13 engineered phage clones, namely P9b and 12III1, were chosen for (i) chemical features of amino acids sequences, (ii) rearrangements in the secondary structure of their pVIII proteins and (iii) in turn the interactions involved in phage capsid. Then, their resistance to UV-C radiation and hydrogen peroxide (H2O2) was compared to M13 wild-type vector (pC89) without peptide insert. Results showed that both the phage clones acquired an advantage against direct radiation damage, due to a reorganization of interactions in the capsid for an increase of H-bond and steric interactions. However, only P9b had an increase in resistance against H2O2. These results could help to understand the molecular mechanisms involved in the stability of new virus variants, also providing quick and necessary information to develop effective protocols in the virus inactivation for human activities, such as safety foods and animal-derived materials.

Antimicrobial Effect and Cytotoxic Evaluation of Mg-Doped Hydroxyapatite Functionalized with Au-Nano Rods.

Hydroxyapatite (HA) is the main inorganic mineral that constitutes bone matrix and represents the most used biomaterial for bone regeneration. Over the years, it has been demonstrated that HA exhibits good biocompatibility, osteoconductivity, and osteoinductivity both in vitro and in vivo, and can be prepared by synthetic and natural sources via easy fabrication strategies. However, its low antibacterial property and its fragile nature restricts its usage for bone graft applications. In this study we functionalized a MgHA scaffold with gold nanorods (AuNRs) and evaluated its antibacterial effect against S. aureus and E. coli in both suspension and adhesion and its cytotoxicity over time (1 to 24 days). Results show that the AuNRs nano-functionalization improves the antibacterial activity with 100% bacterial reduction after 24 h. The toxicity study, however, indicates a 4.38-fold cell number decrease at 24 days. Although further optimization on nano-functionalization process are needed for cytotoxicity, these data indicated that Au-NRs nano-functionalization is a very promising method for improving the antibacterial properties of HA.

A new Ag-nanostructured hydroxyapatite porous scaffold: Antibacterial effect and cytotoxicity study.

We report a new chemical method for the functionalization of Mg-hydroxyapatite (Mg-HA) scaffold with Ag nanoparticles (Ag NPs) integrating in one step both the synthesis of the Ag NPs and their nano-structuring into the HA matrix (Ag-Mg-HA scaffold). This method exploits a green photochemical synthesis and allows the direct growth of Ag NPs on the Mg-HA surface. The surface structure of Ag-Mg-HA scaffold, investigated by scanning electron microscopy, shows no significant changes in the morphology upon Ag NPs incorporation. The presence of Ag was confirmed by EDX analysis. TEM and spectroscopic investigations show Ag NPs spherical shaped with a mean diameter of about 20 nm exhibiting the typical plasmon absorption band with maximum at 420 nm. The antibacterial properties of Ag-Mg-HA scaffolds were tested against two bacterial strains, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results show excellent antibacterial properties achieving up to 99% and 100% reduction of colonies for both bacteria cultures after 24 h of incubation and 100% of reduction after 48 h of incubation. The cytotoxicity of Ag-Mg-HA was also in deep investigated assessing both cell proliferation and differentiation using hADSCs (human Adipose Derived Stem Cells) and testing data point at 0, 7, 14 and 24 days. The results show cytotoxic effect with cell proliferation decreasing up to 90% at 24 days and osteogenic differentiation inhibition. The observed cytotoxicity can be probable ascribed to the oxidative stress by ROS. Indeed, considering the effectiveness of the nanofunctionalization method and the excellent antibacterial properties showed by the Ag-Mg-HA scaffold, future works will be devoted to create nanofunctionalized scaffold satisfying both antimicrobial and osteo-regenerative properties.

Au, Pd and maghemite nanofunctionalized hydroxyapatite scaffolds for bone regeneration.

Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering (BTE) allowing the incorporation of nanomaterials able to improve cell proliferation and differentiation. In this study, Mg-HA-Coll type I scaffolds (Mg-HA-based scaffolds) were nanofunctionalized with gold nanorods (Au NRs), palladium nanoparticles (Pd NPs) and maghemite nanoparticles (MAG NPs). Nanofunctionalized Mg-HA-based scaffolds (NF-HA-Ss) were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells (hADSCs). Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control (Mg-HA-based scaffold), whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%, respectively. Similar evidences were found for the osteoinductive properties showing relevant calcium deposits (25% higher than the control) for MAG nanofunctionalization, while a decreasing of cell differentiation (20% lower than the control) for both Au NRs and Pd NPs derivatization. These results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au NRs. The excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG NPs. These findings may pave the way for the development of innovative nanostructured scaffolds for BTE.

Effects of Heavy Ion Particle Irradiation on Spore Germination of Bacillus spp. from Extremely Hot and Cold Environments.

Extremophiles are optimal models in experimentally addressing questions about the effects of cosmic radiation on biological systems. The resistance to high charge energy (HZE) particles, and helium (He) ions and iron (Fe) ions (LET at 2.2 and 200 keV/µm, respectively, until 1000 Gy), of spores from two thermophiles, Bacillushorneckiae SBP3 and Bacilluslicheniformis T14, and two psychrotolerants, Bacillus sp. A34 and A43, was investigated. Spores survived He irradiation better, whereas they were more sensitive to Fe irradiation (until 500 Gy), with spores from thermophiles being more resistant to irradiations than psychrotolerants. The survived spores showed different germination kinetics, depending on the type/dose of irradiation and the germinant used. After exposure to He 1000 Gy, D-glucose increased the lag time of thermophilic spores and induced germination of psychrotolerants, whereas L-alanine and L-valine increased the germination efficiency, except alanine for A43. FTIR spectra showed important modifications to the structural components of spores after Fe irradiation at 250 Gy, which could explain the block in spore germination, whereas minor changes were observed after He radiation that could be related to the increased permeability of the inner membranes and alterations of receptor complex structures. Our results give new insights on HZE resistance of extremophiles that are useful in different contexts, including astrobiology.

Early palliative care in haematological patients: a systematic literature review.

BACKGROUND: Early palliative care together with standard haematological care for advanced patients is needed worldwide. Little is known about its effect. The aim of the review is to synthesise the evidence on the impact of early palliative care on haematologic cancer patients' quality of life and resource use. PATIENTS AND METHODS: A systematic review was conducted. The search terms were early palliative care or simultaneous or integrated or concurrent care and haematological or oncohaematological patients. The following databases were searched: PubMed, Embase, Cochrane, CINHAL and Scopus. Additional studies were identified through cross-checking the reference articles. Studies were in the English language, with no restriction for years. Two researchers independently reviewed the titles and abstracts, and one author assessed full articles for eligibility. RESULTS: A total of 296 studies titles were reviewed. Eight articles were included in the synthesis of the results, two controlled studies provided data on the comparative efficacy of PC interventions, and six one-arm studies were included. Since data pooling and meta-analysis were not possible, only a narrative synthesis of the study results was performed. The quality of the two included comparative studies was low overall. The quality of the six non-comparative studies was high overall, without the possibility of linking the observed results to the implemented interventions. CONCLUSIONS: Studies on early palliative care and patients with haematological cancer are scarce and have not been prospectively designed. More research on the specific population target, type and timing of palliative care intervention and standardisation of collected outcomes is required. PROSPERO REGISTRATION NUMBER: CRD42020141322.