Granular cell tumor of the neurohypophysis presenting as a third ventricle mass.

Granular cell tumors of the neurohypophysis (GCT) are rare benign neoplasms belonging, along with pituicytoma and spindle cell oncocytoma, to the family of TTF1-positive low-grade neoplasms of the posterior pituitary gland. GCT usually present as a solid sellar mass, slowly growing and causing compressive symptoms over time, occasionally with suprasellar extension. They comprise polygonal monomorphous cells with abundant granular cytoplasm, which is ultrastructurally filled with lysosomes. Here we report the case of a GCT presenting as a third ventricle mass, radiologically mimicking chordoid glioma, with aberrant expression of GFAP and Annexin-A, which lends itself as an example of an integrated diagnostic approach to sellar/suprasellar and third ventricle masses.

Feasibility of Early Active Rehabilitation for Concussion Recovery in Youth: A Randomized Trial.

OBJECTIVE: The primary objective is to evaluate the feasibility (safety and acceptability) of implementing early active rehabilitation (AR) for concussion management in youth with symptoms persisting 2 weeks after injury. A secondary and exploratory objective was to estimate the potential efficacy of early AR compared with standard AR. We hypothesize that AR at 2-weeks postconcussion will be safe and acceptable to patients. DESIGN: Randomized clinical trial. SETTING: The Montreal Children's Hospital of the McGill University Health Center (MCH-MUHC), a tertiary care pediatric teaching hospital affiliated with McGill University in Montreal, Canada. PARTICIPANTS: Twenty youth aged 9 to 17 years old with postconcussion symptoms for at least 2 weeks. INTERVENTION: Active rehabilitation (aerobic exercise, coordination drills, visualization, and education/reassurance) was administered by physiotherapists in-person, and then continued as a home program. METHODS: Twenty participants were randomized to either early AR (initiated 2 weeks after injury) or standard AR (initiated 4 weeks after injury). RESULTS: Two adverse events (one in each group) were identified through an online survey more than one-month postconcussion. Postconcussion symptoms decreased over time for both groups. CONCLUSIONS: The results from this pilot study indicate that a full clinical trial estimating the efficacy of early AR (starting 2 weeks after injury) is feasible. Further study is needed to determine the superiority of this strategy over current treatment approaches.

The cellular effects of Pulsed Electromagnetic Fields on osteoblasts: A review.

Electromagnetic fields (EMFs) have long been known to interact with living organisms and their cells and to bear the potential for therapeutic use. Among the most extensively investigated applications, the use of Pulsed EMFs (PEMFs) has proven effective to ameliorate bone healing in several studies, although the evidence is still inconclusive. This is due in part to our still-poor understanding of the mechanisms by which PEMFs act on cells and affect their functions and to an ongoing lack of consensus on the most effective parameters for specific clinical applications. The present review has compared in vitro studies on PEMFs on different osteoblast models, which elucidate potential mechanisms of action for PEMFs, up to the most recent insights into the role of primary cilia, and highlight the critical issues underlying at least some of the inconsistent results in the available literature. Bioelectromagnetics. 2019;9999:XX-XX. © 2019 Bioelectromagnetics Society.

The integration of orthodontic miniscrews under mechanical loading: a pre-clinical study in rabbit.

INTRODUCTION: Orthodontic miniscrews are an increasingly popular choice to achieve absolute anchorage. The temporary use of miniscrews and their recent introduction have limited the debate over the biological aspect of the materials to that of the surface that permeates the field of dental implants. The aim of the present study was to investigate the integration of grade 5 titanium mini-implants with machined or sand blasted acid etched surface (SAE) under mechanical load in a rabbit tibia model of implant integration. METHODS: A total of 64 miniscrews (Ti6Al4V) of 1.5 mm diameter and 6.5 mm length were inserted in the proximal medial surface of each tibia in eight male rabbits aged 6 months. Each tibia received four miniscrews. A 100 g nickel-titanium coil spring (Neosentalloy) was applied between two miniscrews along the main axis while two miniscrews were left unloaded. The removal torque was measured for loaded and unloaded miniscrews after 12 weeks. Two miniscrews were harvested for histology. RESULTS: Removal torque was significantly higher for SAE mini-implants than for machined screws, under both loading conditions. Although no difference in bone to implant contact was observed among the groups, cortical area significantly decreased with both surfaces under loading. CONCLUSIONS: Our data indicate that SAE miniscrews have higher bone retention than MA miniscrews, although the effects of mechanical loading of these devices on cortical bone require further investigations.

CeF3-ZnO scintillating nanocomposite for self-lighted photodynamic therapy of cancer.

We report on the synthesis and characterization of a composite nanostructure based on the coupling of cerium fluoride (CeF3) and zinc oxide (ZnO) for applications in self-lighted photodynamic therapy. Self-lighted photodynamic therapy is a novel approach for the treatment of deep cancers by low doses of X-rays. CeF3 is an efficient scintillator: when illuminated by X-rays it emits UV light by fluorescence at 325 nm. In this work, we simulate this effect by exciting directly CeF3 fluorescence by UV radiation. ZnO is photo-activated in cascade, to produce reactive oxygen species. This effect was recently demonstrated in a physical mixture of distinct nanoparticles of CeF3 and ZnO [Radiat. Meas. (2013) 59:139-143]. Oxide surface provides a platform for rational functionalization, e.g., by targeting molecules for specific tumors. Our composite nanostructure is stable in aqueous media with excellent optical coupling between the two components; we characterize its uptake and its good cell viability, with very low intrinsic cytotoxicity in dark.

Chitosan-based scaffold modified with D-(+) raffinose for cartilage repair: an in vivo study.

BACKGROUND: Osteochondral defects significantly affect patients' quality of life and represent challenging tissue lesions, because of the poor regenerative capacity of cartilage. Tissue engineering has long sought to promote cartilage repair, by employing artificial scaffolds to enhance cell capacity to deposit new cartilage. An ideal biomaterial should closely mimic the natural environment of the tissue, to promote scaffold colonization, cell differentiation and the maintenance of a differentiated cellular phenotype. The present study evaluated chitosan scaffolds enriched with D-(+) raffinose in osteochondral defects in rabbits. Cartilage defects were created in distal femurs, both on the condyle and on the trochlea, and were left untreated or received a chitosan scaffold. The animals were sacrificed after 2 or 4 weeks, and samples were analysed microscopically. RESULTS: The retrieved implants were surrounded by a fibrous capsule and contained a noticeable inflammatory infiltrate. No hyaline cartilage was formed in the defects. Although defect closure reached approximately 100% in the control group after 4 weeks, defects did not completely heal when filled with chitosan. In these samples, the lesion contained granulation tissue at 2 weeks, which was then replaced by fibrous connective tissue by week 4. Noteworthy, chitosan never appeared to be integrated in the surrounding cartilage. CONCLUSIONS: In conclusion, the present study highlights the limits of D-(+) raffinose-enriched chitosan for cartilage regeneration and offers useful information for further development of this material for tissue repair.

The diffusion-weighted imaging and 11-C-methionine positron emission tomography depiction of an endodermal cyst at the cervico-medullary junction.

A case of a 52-year-old male with left-sided neck pain, vertigo and gait instability is reported. A MRI scan revealed an intra-dural mass at the cervico-medullary junction, further characterised by diffusion-weighted imaging and 11-C-methionine positron emission tomography. Pathological diagnosis was endodermal cyst. The clinico-surgical relevance of the imaging findings is discussed.

Biomimetic coating with phosphoserine-tethered poly(epsilon-lysine) dendrons on titanium surfaces enhances Wnt and osteoblastic differentiation.

OBJECTIVES: Phosphoserine-based functionalization has been proposed as a tool to improve integration of endosseous implants by promoting osteoblast adhesion and differentiation in vitro. The present work investigates whether phosphoserine-tethered poly(epsilon-lysine) dendrons, when applied as a film to titanium surfaces, enhance the differentiation of osteoblastic cells and the activation of Wnt/ß-catenin signaling. MATERIALS AND METHODS: These films were tested in a murine model of calvaria-derived MC3T3 osteoblastic cells, primary bone marrow cells and mesenchymal, undifferentiated C2C12 cells. Gene expression was assayed by Real Time PCR, and activation of Wnt signaling pathway was measured with a reporter assay. RESULTS: Dendrons increased expression of alkaline phosphatase and osteocalcin, two osteoblastic markers, in both murine osteoblastic MC3T3 cells and primary bone marrow cells. The expression of osteoprotegerin, a protein opposing osteoclastogenesis was also significantly higher in cells growing on dendron-coated substrates both at 3 and 6 days of culture. Similarly, the mRNA levels of Wisp-2 and of ß-catenin, two Wnt target genes, were also markedly increased in this group at day 6. The activation of this signaling pathway in cells growing on the dendron-coated surfaces was confirmed by use of a TCF/ß-catenin reporter system in the C2C12 cell line. CONCLUSIONS: The findings of the present study show that phosphoserine-tethered poly(epsilon-lysine) dendron films act as stimuli for the activation of specific signal cascades and promote the differentiation of adhering progenitor cells into an osteoblastic phenotype.

Concerted electron/proton transfer mechanism in the oxidation of phenols by laccase.

This study aimed to assess structural requirements in the enzyme/substrate interactions that are responsible for tuning the enzymatic reactivity. To better assess the role of the aspartic residue in the substrate-binding pocket of basidiomycete-type laccases, we compared the catalytic efficiency of wild-type enzymes to that of a mutant in which carboxylic acid residue Asp206 was changed to alanine. Oxidation efficiency towards phenolic substrates by laccases of Trametes villosa, Trametes versicolor and a T. versicolor D206A mutant was studied at two pH values. By the Hammett approach and Marcus analysis, we obtained unambiguous evidence that the oxidation takes place by a concerted electron/proton transfer (EPT) mechanism, and that at pH 5 (optimum pH for enzyme activity) the phenolic proton is transferred to Asp206 during the concerted electron/proton transfer process.

Epilepsy surgery of focal cortical dysplasia-associated tumors.

The goal of the present study was to evaluate the clinical characteristics and postoperative seizure outcome of epileptogenic tumors associated with focal cortical dysplasias (FCDs) compared to both solitary FCD type I and solitary tumors. Particular attention is given to FCD type IIIb (tumors associated with FCD type I), which have been recently classified as a separate entity. We retrospectively reviewed the clinical charts of 1,109 patients who were operated on for drug-resistant focal epilepsy, including 492 patients with a histologic diagnosis of solitary FCD I and II (83 and 157 cases, respectively), solitary tumors (179 cases), and FCD-associated tumors (73 cases, 58 of which met the criteria of FCD IIIb of the new International League Against Epilepsy [ILAE] classification). The different subgroups were evaluated for clinical characteristics and postoperative surgical outcome. Clinical variables and postoperative seizure outcome of patients with coexisting tumor and FCDs (FCD IIIb and tumor associated FCD II) were similar to those of patients with a solitary tumor and differed significantly from patients with solitary FCDs. Nevertheless, tumors associated with FCDs are characterized by a striking male predominance and a higher seizure frequency as compared to solitary tumors. Patients with drug-resistant focal epilepsy secondary to a solitary tumor or with a tumor-associated FCD have similar basic clinical presentation and postoperative seizure outcome. Nevertheless, the epileptogenic contribution of the associated FCDs can be crucial, and it needs to be adequately assessed. The impact of FCD on tumor-related epilepsy deserves future research in order to optimize the surgical strategies aimed at seizure relief.

Serotonin: a novel bone mass controller may have implications for alveolar bone.

As recent studies highlight the importance of alternative mechanisms in the control of bone turnover, new therapeutic approaches can be envisaged for bone diseases and periodontitis-induced bone loss. Recently, it has been shown that Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as antidepressants, can positively or negatively affect bone loss in rat models of induced periodontitis. Serotonin is a neurotransmitter that can be found within specific nuclei of the central nervous system, but can also be produced in the gut and be sequestered inside platelet granules. Although it is known to be mainly involved in the control of mood, sleep, and intestinal physiology, recent evidence has pointed at far reaching effects on bone metabolism, as a mediator of the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme required for serotonin synthesis, thus increasing serum levels of serotonin. Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their proliferation by activating PKA and CREB.Although different groups have reported controversial results on the existence of an Lrp5-serotonin axis and the action of serotonin in bone remodeling, there is convincing evidence that serotonin modulators such as SSRIs can affect bone turnover. Consequently, the effects of this drug family on periodontal physiology should be thoroughly explored.

Modeling new trends in bone regeneration, using the BERTopic approach.

Aim: Bibliometric surveys are time-consuming endeavors, which cannot be scaled up to meet the challenges of ever-expanding fields, such as bone regeneration. Artificial intelligence, however, can provide smart tools to screen massive amounts of literature, and we relied on this technology to automatically identify research topics. Materials & methods: We used the BERTopic algorithm to detect the topics in a corpus of MEDLINE manuscripts, mapping their similarities and highlighting research hotspots. Results: Using BERTopic, we identified 372 topics and were able to assess the growing importance of innovative and recent fields of investigation such as 3D printing and extracellular vescicles. Conclusion: BERTopic appears as a suitable tool to set up automatic screening routines to track the progress in bone regeneration.

Primary Large B-Cell Lymphoma of Immune-Privileged Sites of the Cerebellum: A Case Series and Review of the Literature.

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is a rare malignant hematological neoplasm. Involvement of the cerebellum is even rarer and its diagnosis is often difficult to make due to its non-specific clinical and radiological presentation. METHODS: We reported 3 cases of cerebellar IP-LBCL followed at our hospital and reviewed the medical literature to unravel the peculiarities of this poorly studied entity. OUTCOMES: Analyzing our cases and reviewing the literature, we could collect and study 26 cases of cerebellar IP-LBCL. To the best of our knowledge, this is the largest cohort of such patients currently published. CONCLUSION: Cerebellar IP-LBCL presents more often in adult females with cerebellum-related focal neurological signs such as ataxia, headache, and nausea. Histological confirmation is mandatory for a correct diagnosis and treatment and all cases feature diffuse large B-cell lymphoma histopathology. Compared to other encephalic IP-LBCL, cerebellar cases seem to include a higher number of cases with germinal center B-cell phenotype and better survival. These differences may be related to a different immune microenvironment and especially immunoregulation that distinguishes the cerebellum from other areas of the CNS.

Effect of surface treatment on cell responses to grades 4 and 5 titanium for orthodontic mini-implants.

INTRODUCTION: Mini-implants are used to improve orthodontic anchorage, but optimal composition and surface characteristics have yet to be determined. We investigated the behavior of osteoblast-like cells on grade 4 commercially pure titanium and grade 5 titanium alloy with different surface treatments for mini-implants. METHODS: MC3T3 cells were plated on machined, acid-etched, or acid-etched grade 4 titanium enriched with calcium phosphate, or machined, anodized, or anodized and calcium phosphate-enriched grade 5 titanium disks. Surface and cell morphologies were assessed by scanning electron microscopy. Cell viability was measured by chemiluminescence, cytoskeletal organization was investigated by immunofluorescence, and real-time polymerase chain reaction for osteoblast-specific genes was performed to measure cell differentiation. RESULTS: Flattened shapes and strong stress fibers were observed on the machined surfaces; cells on the rough surfaces had a spindle shape, with lower cytoskeletal polarization. Cell proliferation was highest on smooth grade 4 titanium surfaces, whereas cells quickly reached a plateau on rough grade 4 titanium; no difference was observed after 72 hours in the grade 5 titanium groups. Calcium phosphate enrichment on grade 4 titanium significantly increased the messenger RNA levels for alkaline phosphatase and osteocalcin. Osteoblastic markers were higher on the grade 5 titanium machined surfaces than on the rough surfaces, and comparable with acid-etched grade 4 titanium. CONCLUSIONS: Although the grade 4 titanium enriched with calcium phosphate had the highest level of differentiation in vitro, the grade 5 titanium machined surfaces supported cell proliferation and matrix synthesis, and induced high expression of early differentiation markers. Increased mechanical resistance of grade 5 titanium makes it a potential candidate for orthodontic mini-implants.

Tolerable upper intake level for dietary sugars.

Following a request from five European Nordic countries, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was tasked to provide scientific advice on a tolerable upper intake level (UL) or a safe level of intake for dietary (total/added/free) sugars based on available data on chronic metabolic diseases, pregnancy-related endpoints and dental caries. Specific sugar types (fructose) and sources of sugars were also addressed. The intake of dietary sugars is a well-established hazard in relation to dental caries in humans. Based on a systematic review of the literature, prospective cohort studies do not support a positive relationship between the intake of dietary sugars, in isocaloric exchange with other macronutrients, and any of the chronic metabolic diseases or pregnancy-related endpoints assessed. Based on randomised control trials on surrogate disease endpoints, there is evidence for a positive and causal relationship between the intake of added/free sugars and risk of some chronic metabolic diseases: The level of certainty is moderate for obesity and dyslipidaemia (> 50-75% probability), low for non-alcoholic fatty liver disease and type 2 diabetes (> 15-50% probability) and very low for hypertension (0-15% probability). Health effects of added vs. free sugars could not be compared. A level of sugars intake at which the risk of dental caries/chronic metabolic diseases is not increased could not be identified over the range of observed intakes, and thus, a UL or a safe level of intake could not be set. Based on available data and related uncertainties, the intake of added and free sugars should be as low as possible in the context of a nutritionally adequate diet. Decreasing the intake of added and free sugars would decrease the intake of total sugars to a similar extent. This opinion can assist EU Member States in setting national goals/recommendations.

How is the reactivity of laccase affected by single-point mutations? Engineering laccase for improved activity towards sterically demanding substrates.

In spite of its broad specificity among phenols, Trametes versicolor laccase hardly succeeds in oxidizing hindered substrates. To improve the oxidation ability of this laccase towards bulky phenolic substrates, we designed a series of single-point mutants on the basis of the amino-acid layout inside the reducing substrate active site known from the crystal structure of the enzyme. Site-directed mutagenesis has addressed four phenylalanine residues in key positions 162, 265, 332, and 337 at the entrance of the binding pocket, as these residues appeared instrumental for docking of the substrate. These phenylalanines were replaced by smaller-sized but still apolar alanines. A double mutant F162A/F332A was also designed. Measurement of the oxidation efficiency towards encumbered phenols has shown that mutant F162A was more efficient than the wild-type laccase. The double mutant F162A/F332A led to 98% consumption of bisphenol A in only 5 h and was more efficient than the single mutants in the aerobic oxidation of this bulky substrate. In contrast, lack of appropriate hydrophobic interactions with the substrate possibly depresses the oxidation outcome with mutants F265A and F332A. One explanation for the lack of reactivity of mutant F337A, supported by literature reports, is that this residue is part of the second coordination shell of T1 Cu. A mutation at this position thus leads to a drastic coordination shell destabilization. Thermal stability of the mutants and their resistance in a mixed water-dioxane solvent have also been investigated.

Adhesion pattern and growth of primary human osteoblastic cells on five commercially available titanium surfaces.

OBJECTIVE: The aim of this study is to analyze the morphology and proliferation of human osteoblastic cells in vitro on five commercially available titanium surfaces. MATERIALS AND METHODS: Human primary cells of the osteoblastic lineage were obtained from bone explants. The cells were plated on polished (T1), machined (T2), sand-blasted/acid-etched (T3), sand-blasted/acid-etched, modified with hydrogen peroxide rinse (T4), and plasma-sprayed titanium (T5) disks. Cell morphology was studied after 6, 24, 72 h, 7 and 14 days of culture by scanning electron microscopy. The formation and distribution of focal adhesions was investigated by immunocytochemical staining at 3, 6 and 24 h. Cell growth was measured by an MTT assay after 3, 7 and 9 days of culture. Moreover, the production of osteocalcin and osteoprotegerin (OPG) was evaluated in the supernatants by ELISA. RESULTS: Morphological analysis revealed that substrate topography profoundly affected cells' shape and their anchoring structures. Large lamellipodia were formed on polished and machined surfaces, while thin filopodia were more frequently observed on T3 and T4 samples. Moreover, cells formed stronger focal adhesions on T3 and T4 surfaces, and cell proliferation was higher on rough surfaces. Osteocalcin production was higher on the T4 surface, whereas OPG steadily increased on every surface. CONCLUSIONS: Taken together, these data show that all the surfaces allowed cell attachment, adhesion and proliferation, but T4 and T5 surfaces appeared to be a better substrate for the adhesion, proliferation and differentiation of cells of the osteoblastic lineage.

The effects of polydeoxyribonucleotide on wound healing and tissue regeneration: a systematic review of the literature.

Aim: The present study evaluated the effects of polydeoxyribonucleotide (PDRN) on tissue regeneration, paying special attention to the molecular mechanisms that underlie its tissue remodeling actions to better identify its effective therapeutic potential in wound healing. Materials & methods: Strategic searches were conducted through MEDLINE/PubMed, Google Scholar, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials, from their earliest available dates to March 2020. The studies were included with the following eligibility criteria: studies evaluating tissue regeneration, and being an in vitro, in vivo and clinical study. Results: Out of more than 90 articles, 34 fulfilled the eligibility criteria. All data obtained proved the ability of PDRN in promoting a physiological tissue repair through salvage pathway and adenosine A2A receptor activation. Conclusion: Up to date PDRN has proved promising results in term of wound regeneration, healing time and absence of side effects.

3D-printed chitosan scaffolds modified with D-(+) raffinose and enriched with type IV collagen to improve epithelial cell colonization.

Tissue regeneration often requires the use of biocompatible resorbable scaffolds to support the ingrowth of cells from neighboring tissues into a localized tissue defect. Such scaffolds must possess surface molecular cues that stimulate cells to populate the device, the first necessary condition for the formation of a healthy tissue. Chitosan is a natural polymer that has long been tested in biomedical applications because of its high biocompatibility, which can be further increased by modifying its formulation, e.g. adding D-(+) raffinose. We used this formulation in an ad hoc designed 3D printer to create regularly ordered scaffolds, which we then enriched with type IV collagen, an isoform of collagen that is exclusively found in basement membranes. Human epithelial A549 cells were then seeded on control scaffolds or on scaffolds coated with collagen, which was precipitated, or on scaffolds first collagenized and then exposed to either UVB or UVC radiation. Observations by the transmission light microscope, confocal microscope after staining with calcein-AM/propidium iodide, and by environmental scanning electron microscope revealed that collagen-enriched UV-treated scaffolds promoted the attachment of a higher number of cells, which covered a more extensive area of the scaffold, as also confirmed by alamar blue viability assay. Together these data confirm that coating 3D-printed scaffolds made of D-(+) raffinose-modified chitosan with type IV collagen and exposing them to UV light sensibly increases the cell compatibility of scaffolds, making them a better candidate to serve as a tool for the regeneration of epithelia.